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Guidance for the rational

use of antimicrobials
Recommendations for dogs and cats
© Ceva Santé Animale 2016

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Price: £98
ISBN 979-10-92450-05-7

Regulatory information

This guide is not an advertising tool, nor an official or regulatory document.


In all cases, the reader should comply with the applicable laws and regulations, and consult the
medication leaflet or the summary of product characteristics (SPC) before any antibiotic use.
The recommendations contained in this guide are based on the technical, scientific, clinical and
practical information compiled by different experts.
The national legislation that regulates the purchase, prescription, dispensing and use of the antibiotics
mentioned is not presented here. In particular, certain antibiotics mentioned in this book may be
unavailable or even prohibited in certain countries.
The reader is warned that compliance with regulations outweighs the recommendations mentioned
in this book. In this regard, the use of antibiotics shall be compliant with official and local applica-
ble laws and regulations on antibiotic use.
Therefore, the recommendations listed in this guide and the reasoning behind them do not engage the
responsibility of the authors, editors and publishers of this guide. Application of said recommenda-
tions and reasoning are the sole responsibility of the reader. Authors and publisher cannot be
held responsible or co-responsible for any harmful consequences that may result from it.
FOREWORD

FOREWORD
A
ntibiotics and resistance to them among physicians and vets and by uniting
have become a major concern in these two forms of medicine in the “One
recent years. Health” concept that the development of
resistance can be limited and the effica-
What is at stake here? Antibiotics were
cy of antibiotics preserved.
discovered in the 20th century and have
made a greater contribution to ex- The first step is to use antibiotics as lit-
tending life expectancy than any other tle as possible and only as much as nec-
medical treatment. They remain of vital essary to treat infected animals – and
importance today and are irreplacea- humans. Antibiotics should therefore be
ble when it comes to treating infectious reserved only for treating infected ani-
diseases in humans and animals alike. mals further to a precise diagnosis by a
The emergence of resistance to anti- veterinarian.
biotics is a cause of concern, however, Prohibiting the use of antibiotics in vet-
and discoveries of new molecules are erinary medicine would be detrimental
becoming a rarity. Some physicians fear to both animal and human health, as
that there may no longer be any effective 60% of infectious diseases in humans
antibiotics left at all by the end of the 21st have an animal reservoir.
century.
The veterinarian is therefore central
Humans and animals live in close con-
to the decision-making process by
tact, share the same germs and can
making the right diagnosis, choosing
transmit them to each other, including
the best antibiotic to prescribe to the
those that contain resistance genes.
right patient, at the right time and
It is therefore by ensuring best practices only for animals that are infected.

4 5
e
Right P rson
FOREWORD

FOREWORD
SUPPORTING fact sheets proposing a rational thera- Salvador Cervantes, Luca Guardabassi,
the role of the peutic approach for each disease that is Angie Hibbert, Hervé Lefebvre, Ana
veterinarian diagnosed, including the first and sec- Mateus, Chiara Noli, Tim Nuttall, Con-
ond-line antibiotics and avoiding the stança Pomba and Bianka Schulz. The
most critical molecules whenever pos- keen interest and presence at meetings
sible. of the International Cat Care, the Fed-
Right Future

These 37 sheets are accompanied by 29

Right Time
eration of European Companion Animal
Rational precise, practical recommendations.
SERVICE OFFER: Veterinary Associations (FECAVA) and
R&D: prescription Diagnostic Tools /
Finally, 6 synopsis articles review the
fundamentals of microbiology, pharma- the Bella Moss Foundation also provid-
Prevention of Antibiotics Continuing Professional
(Vaccines) Education (CPE) / cology and resistance phenomena. ed precious support, as well as bear-
Alternatives to AB’s Application machines ing testimony to the importance of this
and devices This guide will provide practitioners challenge. Finally, this book would not
with precise, well-supported answers
have been possible without Karin de
to their questions. It provides a useful
Lange and Eric Vandaële who coordinat-
complement to the applicable regula-
tions, although obviously without re- ed the work with the greatest efficiency.
WIDE RANGE
of molecules placing them. Ceva is a responsible player in public
produced to top
quality standards We would like to thank the ten experts health and if we have produced this
who put all their professionalism and guide, it is to ensure that antibiotics carry
conviction into this work: Hervé Brissot, on saving lives in the future.

Rig h
t Product
It is along this far-from-easy road to- rational possible prescription of antibi-
Dr. Mélanie Belliard Dr. Elodie Ollivier
wards rational prescription that Ceva Global Marketing Manager Global Technical Manager
otics in canine and feline medicine and
wishes to accompany veterinarians Ceva Santé Animale Ceva Santé Animale
surgery.
through this GRAM (Guidance for Ra-
tional use of AntiMicrobials) guide for The discussions were often lively between
companion animals. microbiologists, pharmacologists, der-
matologists, internal medicine special-
In 2015, Ceva brought together a mul- ists and surgeons.
ti-disciplinary group of ten experts from
7 European countries in order to reflect, In the end, the group of experts co-pro-
in total independence, upon the most duced 37 clinical best practice guidance

6 7
EDITORIAL
EDITORIAL

EDITORIAL
Antibiotics: three key issues at stake
Karin de Lange, a qualified veterinarian (Ghent 1987).
After several years in mixed and companion animal practice in the UK,
there is only “One World, One Health, teamwork of a European expert panel
she moved to France where she worked as a European Editor for a vet-
One Medicine” for the medical and vet- of recognised practitioners and aca-
erinary publishing company. She has been self-employed in the field of
written communication in animal health at European level since 1999. erinary practitioners of the world. Sci- demics including pharmacologists, mi-
Her clients include European veterinary organisations and expert groups, entists and, increasingly, political deci- crobiologists, and several specialists
publishers and members of the animal health industry. sion-makers, no longer separate both of clinical medicine such as dermatol-
medical disciplines in terms of antibiot- ogists, surgeons and internal medicine
ic resistance... specialists.
Eric Vandaele, a veterinarian by training.
Eric started his career teaching veterinary pharmacy at the veterinary n The third issue is an ethical and legal The recommendations proposed have
school in Nantes. As a scientific journalist and consultant, he closely fol- one. Physicians are asked to make ef- been established collectively, following
lows all matters related to veterinary medicines and legislation. He has forts in order to decrease antibiotic con- a preparatory work by the experts based
coordinated numerous round tables and consensus conferences. sumption and veterinarians are asked to both on scientific publications and their
do likewise. They can no longer ignore professional experience, as well as a
that their prescription practices are, and two-day consensus meeting on the 3rd

F
will increasingly be, closely scrutinised and 4th of December 2015.
or veterinarians, whether in that in humans. It is futile and pointless by health agencies and surveillance au-
large or small animal practice, for physicians to accuse veterinarians of thorities. Veterinary prescribing practices This guide is not intended to be the only
there are three key issues at being the cause of resistance in humans. must therefore be entirely rational, ev- reference in the field of antibiotic thera-
stake regarding antibiotic therapy and It is just as futile and pointless for veter- idence based and therefore irrefutable... py in cats and dogs, however a common
the management of resistance. inarians to deny the transfer of resistant voice always carries louder and further
bacteria from humans to animals and The ambitious aim of this project is to than someone singing alone.
n The first issue is medical. Our medical vice-versa. We all live in the same mi- mobilise companion animal veterinar-
colleagues keep repeating it over and ians with regards to these three key
crobial environment and we exchange
over again, in meetings and in the me- issues, by creating this GRAM book of
our microbes, whether or not carriers
dia: the development of resistance is good antibiotic practices in cats and
of resistance, with each contact, each
reducing their arsenal which is required dogs. This guide is the result of the
handshake, each pat or lick. The glo-
to save certain patients. It is too often
balisation of exchanges, the multipli-
forgotten: antibiotics save lives, both of
cation of travel and contacts explain
humans and animals, and it is this es-
why emerging diseases, most of which
sential advantage that justifies combat-
are shared by animals and people,
ing wasteful use whether caused by bad
practice or unnecessary treatment. spread around the globe within a few
weeks. Unless living in a bubble, this of
n The second issue, public health, is also course also applies to those sharing the
at stake, because the microbial world in same household, crèche, hospital, com-
animals is not completely isolated from munity, region or country... In other words,

8 9
GRAM EXPERT PANEL
Hervé Brissot, DEDV, Dip ECVS, MRCVS European Specialist in
GRAM EXPERTS

GRAM EXPERTS
Small Animal Surgery
Hervé Brissot graduated in the UK since 2006 in different referral set-
from the Veterinary School tings.
of Toulouse in France in Hervé is mainly interested in soft tissue
1994. Since then he has surgery and especially oncosurgery, lung
pursued his interest and surgery and mini-invasive surgery. He has
training in small animal surgery. published original papers in peer reviewed
Dr Hervé Brissot Dr Salvador Cervantes Prof Luca Guardabassi Hervé became a Diplomate from the Euro- international veterinary journals and text-
Surgery Internal Medicine Microbiology
Derby Barcelona Copenhagen / St. Kitts pean College of Veterinary Surgeons in 2005 books, and has spoken and lectured at UK
and is a European Recognised Specialist in and European congresses.
Small Animal Surgery. He has been working

Salvador Cervantes, DVM


Dr Angie Hibbert Prof Hervé Lefebvre Dr Ana Mateus
Feline Medicine Pharmacology Epidemiology & Public Health Salvador Cervantes qualified of Feline Practitioners, the Spanish Study
Bristol Toulouse Hatfield
as a veterinarian in 1998 Group of Feline Medicine (GEMFE) and Com-
from the Autonomous Uni- panion Animal Clinics committee member
versity of Barcelona (UAB), of the statutory body, the Colegio Oficial de
followed by an internship Veterinarios de Barcelona.
at the Companion Animal In 2001, he founded a companion animal
Hospital of the same institution.
practice in central Barcelona, with a strong
He has a particular interest in therapeutics, interest in internal medicine. He is the au-
anaesthesia, pain control and feline medi- thor of the 2012 textbook on small animal
Dr Chiara Noli Dr Tim Nuttall Dr Constança Pomba cine, and he recently obtained Accreditation geriatrics (in Spanish), Manual de Geriatria
Dermatology Dermatology Internal Medicine as Specialist in Feline Medicine in Spain Canina y Felina. In 2016, he co-founded the
Turin Edinburgh Lisbon (Acred Med Fel AVEPA). Clinica Felina Barcelona, a cats-only hospi-
He is a member of the American Association tal in Barcelona, Spain.

Dr Bianka Schulz
Internal Medicine
Munich

10 11
Luca Guardabassi DVM, PhD, Dip ECVPH Hervé Lefebvre, DVM, PhD, HDR, Dip ECVPT
GRAM EXPERTS

GRAM EXPERTS
Luca Guardabassi is a mi- prevention of bacterial infections in animals. Hervé Lefebvre is Professor His current research interests are drug
crobiologist and Professor He has published 5 book chapters and over in physiology at the De- pharmacokinetics, renal and cardiovascular
of Clinical Microbiology at 110 peer-reviewed articles in scientific jour- partment of Physiology and pharmacology, kidney and cardiovascular
the Ross University School nals. He is also Editor of the book Guide to Therapeutics, National Vet- functional testing, and early diagnosis of
of Veterinary Medicine in St Prudent Antimicrobial Use in Animals, pub- erinary School of Toulouse chronic kidney disease in at-risk popula-
Kitts, West Indies and Ad- lished by Wiley-Blackwell in 2008. (ENVT), France. He is also tions, reflected in over 100 original peer-re-
junct Professor at the University of Copen- He is currently principal investigator of a head of the Clinical Research Unit at ENVT. viewed articles and book chapters.
hagen. One Health interdisciplinary research centre He obtained his DVM from the ENVT, France, Hervé received the ESVNU-Hill’s Excellence in
He graduated in Veterinary Medicine at the for control of antibiotic resistance (UC-Care) in 1988. He received his PhD in 1994. He Veterinary Nephrology and Urology Award at
University of Pisa in 1994, obtained his PhD and coordinator of an EU Initial Training became Diplomate of the European Col- the 2006 ECVIM-CA congress.
in Microbiology at the University of Copenha- Network in the area of antimicrobial drug lege of Veterinary Pharmacology and Toxi- He was a member of the expert panel of the
gen in 2000 and became de-facto Diplomate R&D (TRAIN-ASAP). He is also chairman of cology in 2000. He is Board member of the French GRAM book.
of the European College of Veterinary Public the European Society of Clinical Microbiolo- International Renal Interest Society (IRIS).
Health (ECVPH) in 2005. He was associate gy and Infectious Diseases (ESCMID) Study
professor, then professor in Antimicrobial Group for Veterinary Microbiology (ESGVM),
Resistance and Antibiosis at the University member of international veterinary commit-
of Copenhagen from 2005 to 2015. tees for antimicrobial susceptibility testing
His research interests focus on improving (CLSI and VetCAST) and of national and in-
understanding of the evolution and epidemi- ternational working groups for antimicrobial Ana Mateus, LMV, MVPH, PhD, Dip ECVPH
ology of multidrug-resistant bacteria of clin- guidelines in veterinary medicine, and sec-
ical or zoonotic interest and on development tion editor for the Journal of Global Antimi- Ana Mateus is a lecturer in public health teaching of undergraduate stu-
of new strategies for diagnosis, therapy and crobial Resistance. Veterinary Public Health and dents.
part of the Veterinary Epi- In October 2011, Ana pursued a traineeship at
demiology, Economics and the European Medicines Agency (EMA) with
Angie Hibbert, BVSc(Bristol), CertSAM, Dip ECVIM-CA, RCVS Public Health group at the the veterinary unit where she was involved in
Specialist in Feline Medicine Royal Veterinary College in projects monitoring antimicrobial use and an-
London. Her main interests are foodborne dis- timicrobial resistance in food-producing and
Angie Hibbert graduated veterinary undergraduates in clinical rota-
eases, zoonoses and antimicrobial resistance. companion animals. Between 2012 and 2014,
from the University of Bris- tions.
tol in 2000 with distinction. Ana completed her Veterinary Medicine degree she worked in Public Health England as a Field
Angie enjoys all aspects of feline internal
After 5 years in general in 2001 in the Technical University of Lisbon, Epidemiology Training Program (FETP) fellow.
medicine and small animal emergency care.
small animal practice, she Portugal. She first worked for two years as a In 2012, Ana completed a PhD on the extent
She runs the radioiodine service and is pas-
returned to Langford (Bristol) to under- companion animal and exotic pets practition- and patterns of antimicrobial usage in dogs
sionate about feline geriatric care. Angie has
take an International Cat Care (formerly er in Milan, Italy. In 2003, she moved to the UK and cats in the UK.
published in this area and spoken extensive-
and worked for over 2 years in food safety and She is member of the FECAVA working group
Feline Advisory Board) residency in feline ly at British and European veterinary meet-
meat hygiene. In 2005, she enrolled in a resi- on hygiene and the use of antimicrobials in
medicine. She became a Diplomate of the ings, with particular focus on feline hyper-
dency program in Veterinary Public Health by veterinary practice, which developed guidance
European College of Veterinary Internal thyroidism. She is a member of the Journal
the University of Glasgow Faculty of Veterinary posters for veterinary practitioners.
Medicine in 2008 and an RCVS Recognised of Feline Medicine and Surgery’s editorial
Medicine, where she was actively involved in
Specialist in Feline Medicine in 2010. She board. Her research interests include feline
currently is the clinical lead for the Feline hyperthyroidism, antibiotic use in practice
Centre at the University of Bristol, receiving and evaluating the welfare of cats in the hos-
referrals, supervising residents and teaching pital environment.

12 13
Chiara Noli, DVM, Dip ECVD Constança Pomba, DVM, PhD
GRAM EXPERTS

GRAM EXPERTS
Chiara Noli graduated in of the International Society of Veterinary Constança Pomba is As- Party (AWP/CVMP), formerly known as SAGAM.
veterinary medicine from Dermatopathology and of the World Asso- sociate Professor of Inter- She is a founding member of the Special
the University of Milan, Ita- ciation for Veterinary Dermatology. She is nal Medicine, Department Interest Group Medical Felina (GIEFEL) and
ly, in 1990. After a residency currently Board Member of the European of Clinical and Hospital Special Interest Group of Internal Medicine
at the University of Utrecht, College of Veterinary Dermatology. School of the Faculty of (GIEMINT) of the Portuguese Association
the Netherlands, she ob- Chiara is author of more than 100 articles Veterinary Medicine, Uni- of Veterinary Medical Specialists in Animal
tained the European Diploma in Veterinary in Italian and international journals, of nine versity of Lisbon (FMV-U Lisboa), Portugal. Company (APMVEAC). She is also a member
Dermatology in 1996. Since then, she has book chapters and three veterinary derma- She graduated from the Faculty of Veteri- of the European Society of Veterinary Inter-
been working as a referral dermatologist tology textbooks, and co-editor of the book nary Medicine of the Technical University of nal Medicine (ESVIM) and the European So-
and dermatopathologist in Northern Italy. Veterinary Allergy published by Wiley (2014). Lisbon in 1991, obtaining a master’s degree ciety of Veterinary Nephrology and Urology
Chiara was President and Founder Member She has given several hundred lectures in Italy in 1994 and her PhD in 2002 at the same (ESVNU).
of the Italian Society of Veterinary Derma- and in other countries spanning three conti- University. She is the author of several publications and
tology, President of the European Society of nents. She is currently Technical Director of the national and international communications
Veterinary Dermatology and Board Member Veterinary Blood Bank and Head of the Lab- on these issues, and is editor of the Jour-
oratory of Antibiotic and Biocide Resistance nal of Antimicrobial Chemotherapy. Her re-
of FMV-U Lisboa. She is also Member of the search interests include internal medicine,
Scientific Advisory Group on Antimicrobials antimicrobial resistance and therapy and
of the European Medicine Agency (EMA) and bacterial pathogenesis.
Vice-chair of the EMA Antimicrobial Working
Tim Nuttall Bsc, BVSc, CertVD, PhD, Cbiol, MSB, MRCVS
RCVS Specialist in Veterinary Dermatology
Tim Nuttall graduated from and presented over 100 lectures throughout Bianka Schulz, DVM, Dr habil., Dip ECVIM-CA (Internal Medicine)
the University of Bristol in the world. In addition, Tim has served on
1992 and originally joined RCVS, BSAVA, ESVD and DEFRA scientific Bianka Schulz obtained her became lecturer in internal medicine at the
the Dick Vet in 1995 to train committees, the International Committee DVM from the Ludwig Max- LMU. In 2007 she became Diplomate of the Eu-
in dermatology and study on Atopic Diseases in Animals. He is a sci- imilian University in Munich ropean College of Veterinary Internal Medicine
for a PhD on canine atopic dermatitis. He entific advisor to the Bella Moss Foundation in 1997. Following an intern- for Companion Animals (ECVIM-CA).
joined the University of Liverpool in 2001, and has been a co-editor of the journal Vet- ship and residency in inter- Her research interests include respiratory dis-
developing a dermatology clinic that now erinary Dermatology. nal medicine at the LMU and ease in dogs and cats, with a particular focus
sees over 1000 cases each year. In August He also has an active research programme, at the Department of Small Animal Medicine at on infectious respiratory diseases, feline asth-
2013 he returned to the Dick Vet as Head of studying antimicrobial resistance, skin in- the University of Georgia in Athens (USA), she ma and antimicrobial therapy.
Dermatology. fections and the genetics of canine atopic
Tim has written over 80 clinical and scientif- dermatitis. In 2014 he received the BSAVA
ic publications, co-authored A Colour Hand- Woodrow Award for outstanding contribu-
book of Skin Diseases of the Dog and Cat, tions to veterinary medicine.

14 15
GRAM OBSERVERS
Federation of European Companion Animal
GRAM observers

GRAM observers
The Federation of European Companion Animal Veterinary Associations (FECAVA)
Veterinary Associations represents more than 25,000 companion animal veterinarians in 40 European
countries. FECAVA is the platform for the promotion of professional development
distributed throughout Europe. They are and the representation of companion animal veterinarians in Europe, and strives
freely available upon request. to improve the veterinary care of pets, to highlight the human-animal bond and
In order to raise awareness on antimi- the “One Health” concept. It does this through professional development, liaisons
crobial resistance among companion with relevant organisations and stakeholders and by facilitating the interaction
animal veterinarians, FECAVA organ- between European companion animal veterinarians.
ised a Hygiene Symposium at the WSA- www.fecava.org www.ejcap.org
VA/FECAVA Congress in Geneva in 2010
and a Symposium on antimicrobial re-
Simon Orr (UK) Monique Megens (NL) sistance at the FECAVA EuroCongress in
FECAVA President FECAVA President Dublin in 2013.
2011-2013 2013-2015 FECAVA is also a long-standing asso-
ciate partner of the European Platform
“Not all infections are caused by bacte- for the Responsible Use of Medicines in
ria: some are viral and do not respond to Animals (EPRUMA).
antibiotics. Also, not all bacterial infec- In short, FECAVA has a solid track re-
tions require antibiotic therapy.” This is cord in combating antimicrobial resist-
one of the warnings for pet owners on ance, one of its top priorities.
the waiting room poster, produced in
It was therefore with great pleasure
2011 by the FECAVA Working Group on
that we heard about the GRAM initiative
Hygiene and the Use of Antimicrobials in
and accepted an invitation to attend the
Practice, in collaboration with the Bel-
meetings of the European GRAM expert
la Moss Foundation. The working group
panel. This has allowed us to witness
(which included Luca Guardabassi and
first-hand the discussions and debates
Ana Mateus) produced four posters al-
that were at its heart. What is ideal
together:
from a scientific viewpoint is not always
- Recommendations for appropriate practical and we were happy to see that
antimicrobial therapy, feasibility was part of the consensual
- Decision tree on whether or not anti- process.
biotics should be used, The European GRAM book is a valua-
- Key recommendations on hygiene in ble, practical tool and we hope that it
practice, will contribute to the responsible use
- Advice to pet owners on responsible of antimicrobials, for the benefit of the
antibiotic use. health of people and their pets - and
The four posters have been translated allow a continued, reliable use of our
into several languages and have been worthy allies in case of need: antibiotics.

16 17
International Society of Feline Medicine The Bella Moss Foundation
GRAM observers

GRAM observers
Andrew Sparkes Jill Moss
BVetMed, PhD, DipECVIM, MANZCVS, MRCVS
Veterinary Director, International Society of Feline Medicine and
International Cat Care
Tisbury, UK.

The International Society of Feline Med- much media coverage. Just as in the The Bella Moss Foundation is a chari- The Bella Moss Foundation does this to
icine is delighted to see the GRAM pro- medical profession, there is a need for ty that promotes prudent antimicrobial save lives and to prevent the spread of
ject initiated by CEVA come to fruition veterinary practitioners to be critical use and hygiene in human and veteri- infections in humans and animals.
with the publication of this multi-author about their use of antibiotics and ensure nary medicine, with the aim to achieve a
The guidance contained within GRAM,
book, written by a number of leading they are not used inappropriately. world where multi-drug resistant bacte-
produced by a Pan-European expert
European experts. ria are a rarity.
This can be challenging, and to have a panel, is consistent with these aims.
The growing threat of antibiotic re- comprehensive and reliable source of The Foundation communicates with the
The Foundation shares Ceva’s commit-
sistance to both human and ani- information (such as this book) will be general public, academic institutions,
ment to responsible and rational use of
mal health is not something that can an invaluable resource for busy practi- government departments and lead-
antimicrobials with the aim of using “as
be ignored and continues to receive tioners… congratulations to all involved! ing researchers around the world on a
little as possible and only as much as
regular basis. It works in collaboration
necessary”. The Bella Moss Foundation
with these and other bodies to provide
is pleased to support the GRAM initia-
education, information and support for
Andy has worked as a feline-only vet since 1987 and trained as a specialist at the tive.
veterinary professionals and animal
University of Bristol. He is a popular speaker and internationally recognised as a
owners to improve infection control,
feline specialist. He has published widely, and in 2004 co-authored Self-Assess-
knowledge and practice.
ment Colour Review of Feline Medicine with Dr Sarah Caney. Andy is the co-editor-
in-chief and founding editor of the Journal of Feline Medicine and Surgery, and in
2012 after being associated with International Cat Care for more than 25 years, he
joined the charity as their full-time Veterinary Director.

18 19
CONTENTS
n Foreword............................................................................................................5 Ophthalmology ................................................................................................. 185

CONTENTS
n Editorial ...........................................................................................................8 n Conjunctivitis and keratitis.........................................................................186
n GRAM expert panel ........................................................................................10 n Infectious uveitis.........................................................................................192
n GRAM observers ............................................................................................16 Digestive system............................................................................................... 199
n Common diarrhoea in dogs and cats.........................................................200
n Gastroenteritis due to bacterial pathogens
part 1 Disease fact sheets..................................... 25 (Campylobacter, Salmonella, Clostridium, E. coli)....................................204
n Hepatobiliary infections..............................................................................210
Urinary and reproductive tract ......................................................................... 27 Surgery ............................................................................................................. 217
n Canine cystitis...............................................................................................28 n Osteomyelitis...............................................................................................218
n Feline (bacterial) cystitis...............................................................................36 n Septic arthritis.............................................................................................226
n Bacterial urinary tract infection in cats with CKD.......................................44 n Wound infections and abscesses...............................................................234
n Pyelonephritis...............................................................................................52 n Septic peritonitis.........................................................................................242
n Canine prostatitis..........................................................................................58 n Post-operative infections............................................................................250
n Epididymitis, orchitis & balanoposthitis.......................................................64 n Prevention of surgical complications
n Metritis and pyometra...................................................................................70 (including peritonitis and abscesses).........................................................258
n Vaginitis.........................................................................................................76 Dentistry............................................................................................................ 269
n Mastitis..........................................................................................................80 n Periodontal disease....................................................................................270
Respiratory tract ................................................................................................ 85
n Canine rhinitis...............................................................................................86
n Canine tracheobronchitis.............................................................................90 part 2 Recommendations.........................................275
n Feline rhinitis and tracheobronchitis...........................................................96
Approach to a suspected bacterial infection.................................................. 277
n Bronchopneumonia and pneumonia..........................................................106
n R1: How do I sample for cytology in cases of
n Pyothorax in dogs........................................................................................114 suspected bacterial infections?..................................................................278
n Pyothorax in cats.........................................................................................122 n R2: How do I interpret cytology results and
Dermatology ..................................................................................................... 131 how should I act upon them?.....................................................................284
n Surface and superficial pyoderma.............................................................132 Bacteriology ..................................................................................................... 289
n Deep pyoderma...........................................................................................138 n R3: When is culture and sensitivity testing of little use,
n Otitis externa and media.............................................................................146 recommended, indispensable?..................................................................290
Internal medicine ............................................................................................. 153 Taking and sending samples ........................................................................... 293
n Prevention of infectious endocarditis.........................................................154 n R4: How should samples for bacterial culture and
n Bacteraemia (sepsis)..................................................................................158 antibiotic sensitivity testing be taken (correctly)?......................................294
n Rare mycobacterial infections....................................................................166 n R5: Is it useful to take a sample in animals undergoing
n Vector-borne bacterial infections...............................................................168 antibiotic treatment?...................................................................................300
n Haemotropic mycoplasmosis.....................................................................172 n R6: What information should be supplied with the sample?
n Feline toxoplasmosis..................................................................................174 Where should the sample be examined?...................................................302
n Pyrexia of unknown origin..........................................................................178 n R7: How should samples be transported?.................................................304

20 21
Interpretation of results .................................................................................. 307 Zoonotic impact................................................................................................. 387

CONTENTS
n R8: How should results be interpreted? Is the classification ‘‘sensitive, n R23: In which cases can resistance selected in dogs and cats
intermediary, resistant’’ predictive of the clinical efficacy?......................308 cause a problem for human health?..........................................................388
n R9: Why is the result of sensitivity testing not always reflected Nosocomial infections...................................................................................... 393
by clinical efficacy?.....................................................................................316 n R24: How to prevent and deal with nosocomial infections
n R10: What should be done if results of sensitivity testing in a veterinary practice? .............................................................................394
diverge from clinical outcome?..................................................................318 Antimicrobial prophylaxis for surgery and critical care................................ 403
Broad-spectrum AM, combinations, de-escalation ...................................... 321 n R25: How can infections be prevented when using indwelling
n R11: Does the use of a broad-spectrum antimicrobial devices (e.g. urinary catheter, IV catheter...)?............................................404
(or combination of antimicrobials) assist in doing without n R26: How can surgical infections be prevented? ......................................408
bacterial sensitivity testing?.......................................................................322 n R27: Am I doing it right? Five tools to assess my surgical
n R12: What are the rules of antibiotic combinations?.................................326 site infection prevention protocol...............................................................412
n R13: Which antimicrobials have a narrow spectrum?...............................330 Recommendations to pet owners.................................................................... 417
n R14: Which therapeutic approach is recommended n R28: What are the recommendations and advice that can be
while awaiting results?...................................................................................334 given to the pet owner?...............................................................................418
Long-acting antimicrobials.............................................................................. 339 n R29: What are the recommendations and advice for owners
n R15: What is the benefit/risk ratio of (very) of premises where pets are kept in groups (breeders, kennels,
long-acting antimicrobials?........................................................................340 catteries…)?.................................................................................................422
Critically important antibiotics ....................................................................... 345
n R16: Under which circumstances may 3rd and 4th generation

cephalosporins and fluoroquinolones be prescribed?..................................346 part 3 Synopsis........................................................................433


Antimicrobial classification............................................................................. 353
n R17: Is it possible to rank antibiotics according to 1st or 2nd choice? n Hygiene and antisepsis in veterinary surgery...............................................434
Yes but... ....................................................................................................354 n Key questions before initiating any antibiotherapy.......................................440
Causes of failure............................................................................................... 361 n Pharmacological basis of antibiotic therapy.................................................452
n R18: What are the key causes of antibiotic treatment failure and n Current situation of antibiotic resistance in dogs and cats,
what is the importance of resistance? What to do in a case of emerging resistance patterns........................................................................462
antibiotic treatment failure?.......................................................................362 n Relevance of multidrug resistant infections for the
Multidrug resistant infections......................................................................... 365 veterinary professional...................................................................................470
n R19: How to deal with multidrug resistant infections?.............................366 n Tables comparing existing guidelines...........................................................478

Prevention of resistance.................................................................................. 373


n R20: How can the development of resistance be limited when

using antibiotics? (timing, dosage, duration).............................................374 part 4 APPENDICES...............................................................497


Compliance........................................................................................................ 377
n R21: How to obtain good client compliance (to limit the development n Classifications and drug index.......................................................................498
of resistance)?.............................................................................................378 n Glossary..........................................................................................................506
n R22: How do I get the pill into the animal? Top ten tips............................382 n References & bibliography.............................................................................518

22 23
Part 1
DISEASE FACT
SHEETS
DISEASE FACT SHEETS

24
DISEASE FACT SHEETS

26
Urinary and
reproductive tract

27

DISEASE FACT SHEETS


CANINE cystitis
Pathogen 2: Staphylococcus spp.
• The majority of bladder infections in dogs are due to a single bacterial species.
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Bacteria involved Amoxicillin 3 5 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


a 4 4 3 = average
Trimethoprim sulfonamides
4 = good
Bacteria Prevalence * Amoxicillin + clavulanate 4 5 5 = excellent
Cefalexin 4 5 Treatment
choice
Escherichia coli 44-60% b b 4 5
Marbofloxacin / Enrofloxacin
1st line
Cefovecinc 4 5
Staphylococcus spp. 11-12%
Nitrofurantoind 5 4 2nd line
Proteus mirabilis 9-12% Pradofloxacinb,e 4 3
Last resort
* large geographical variability Gentamicin f 4 5
Excluded
for this
indication
Antibiotics that can be used
Pathogen 1: Escherichia coli a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear testing
is recommended if use > 3 weeks6.
In vitro Tissue Treatment Sensitivity b Avoid use in growing dogs of large breeds.
Antibiotics that can be used and distribution
sensitivity distribution choice c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
1 = nil sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
Amoxicillin 3 5 2 = weak not possible.
Trimethoprim sulfonamidesa 4 4 3 = average d Nitrofurantoin is a human preparation useful in multi-drug resistant UTIs; use should be guided by culture and
4 = good sensitivity testing and by cascade guidelines.
Amoxicillin + clavulanate 4 5 5 = excellent e Pradofloxacin
is a last resort choice due to its very extended spectrum of activity and should only be used if a
Cefalexin 3 5 Treatment narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
choice f Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Marbofloxacinb / Enrofloxacinb 4 5 www.iris-kidney.com/education/prevention.html).
1 line
st

Cefovecinc 4 5
Nitrofurantoind 5 4 2nd line

Pradofloxacinb,e 5 3
Last resort
Gentamicinf 4 5
Excluded
for this
indication

28 29
CANINE cystitis

Therapeutic approach Treatment recommendations


First choice antibiotic

Urinary cytology - Empirical treatment Antibiotics that


DISEASE FACT SHEETS

DISEASE FACT SHEETS


Pathogen involved Dosage Duration of treatment
can be used
Amoxicillin + clavulanate 12.5-25 mg/kg/12h PO 10-15 mg/kg/24 SC
Escherichia coli Trimethoprim 15 mg/kg/12h PO in7dogs
days
sulfonamidesa (uncomplicated cystitis)
Amoxicillin 15 mg/kg/8-12h PO 28 days
Bacilli Cocci Staphylococcus spp. Trimethoprim 15 mg/kg/12h PO (complicated cystitis)
(assume) Escherichia coli (assume) Staphylococcus spp. sulfonamidesa

Amoxicillin+clavulanate, Amoxicillin,
Second choice antibiotic (with culture and sensitivity testing and only if
trimethoprim sulfonamides trimethoprim sulfonamides
first choice is not an option)
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Culture and sensitivity
Amoxicillin ± clavulanate 10-25 mg/kg/12h PO

Cefalexin 15-30 mg/kg/12h PO


7 days
Escherichia coli Staphylococcus spp. Marbofloxacin b 2 mg/kg/24h PO
(uncomplicated cystitis)
Escherichia coli
Enrofloxacinb 5 mg/kg/24h PO 28 days
Amoxicillin ± clavulanate, Amoxicillin ± clavulanate, Staphylococcus spp.
(complicated cystitis)
trimethoprim sulfonamides trimethoprim sulfonamides Nitrofurantoind 4.4-5 mg/kg/8h PO
8 mg/kg SC for 14d
Cefovecinc (for complicated UTIs
Cefalexin, marbofloxacin, Cefalexin, marbofloxacin, repeat dose after 14d)
enrofloxacin, enrofloxacin, a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear testing
cefovecin, nitrofurantoin cefovecin, nitrofurantoin is recommended if use > 3 weeks6.
b Avoid use in growing dogs of large breeds.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
Pradofloxacin, gentamicin Pradofloxacin, gentamicin sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
not possible.
d Nitrofurantoin is a human preparation useful in multi-drug resistant UTIs; use should be guided by culture and
sensitivity testing and by cascade guidelines.

Urine samples for susceptibility testing should be refrigerated


immediately after collection and submitted to the laboratory as
quickly as possible..

30 31
CANINE cystitis

Diagnostic approach Table 1 - Host urinary defence mechanisms.


n Bacterial cystitis follows the colonisa- urethra. The most common clinical signs Regular and complete micturition
tion of the urinary bladder by (usually) are pollakuria (frequent urination in - Correct laminar flux
aerobic bacteria ascending from the uro- small amounts), stranguria and dysuria. Normal urinary tract anatomy
DISEASE FACT SHEETS

DISEASE FACT SHEETS


genital area. Bacteria persist in the urine Other less common signs are: urinary Intact mucosal defences
or adhere to the urothelium, where they incontinence and haematuria4 (Figure 1). - Glycosaminoglycan layer
will start multiplying. A urinary infection n Classification of UTIs - Cell exfoliation
implies a transitory failure of natural de-
• Simple uncomplicated UTI - sporadic - Ig excreted with urine and urinary surface
fence mechanisms (Table 1)3,8.
infection in an otherwise healthy dog - Normal genito-urinary tract flora
n Although all ages can be affected,
with normal urinary tract anatomy and Antimicrobial properties of urine
prevalence increases with age due to function; treatment 7 days.
the occurrence of other diseases (e.g. - Osmolality
• Complicated UTI - infection in dogs - pH
prostatic disease, kidney disease, endo-
crine disease, tumours…). Bitches are with structural or functional urogenital - Urea concentration (with exception of urease producing bacteria, e.g.
predisposed due to a wider and shorter tract abnormalities, immunosuppression Proteus mirabilis, Staphylococcus spp., Corynebacterium urealyticum,
or comorbid disease that predisposes Ureaplasma spp.)
to UTI or recurrent episodes (> 3 in 12
- Other factors, e.g. Tamm-Horsfall mucoprotein or uromoduline
month period); treatment 28 days.
Systemic immunocompetence
• Subclinical bacteriuria - identification
- This can be decreased in Cushing’s disease, diabetes mellitus, hypothy-
of bacteria on urine culture in the ab-
roidism or by corticosteroid administration.
sence of clinical or cytological signs of
infection9. The clinical significance is not
fully understood and currently treatment
is warranted only in very specific circum-
Reasoning
stances such as immunocompromised n The main factor for choosing an anti- nisms phagocytised by neutrophils) and
patients (e.g. patients with endocrinop- biotic to treat cystitis is its ability to con- test strips, but cannot be ruled out if these
athies) or those with underlying renal centrate in the urine, reaching at least tests are negative (Figures 2, 3 and 4).
disease (N.B. this lacks an evidence base). 4x times the MIC (in an active form!).
n In the absence of sensitivity data,
© Salvador Cervantes

The cornerstone of diagnosis is a com- n For uncomplicated and first-time the use of amoxicillin or TMS as a first
plete urinalysis (test strip, specific grav- cases, it is probably not necessary to choice in both cases (infections by cocci
ity and sediment) and urinary culture of perform culture and sensitivity testing: or bacilli) is justified9.
a urine sample obtained by cystocente- cytology (shape of microorganisms) and
n The use of fluoroquinolones and long-
sis. Test strips usually reveal haema- pH of urine may suffice. However, uri-
turia, proteinuria and give an indication nary culture is the only reliable tool to term cephalosporins (e.g. cefovecin)
Figure 1 - Appearance of different urines. From of urinary pH. confirm or rule out a urinary tract in- should be reserved for cases showing
left: normal urine; severe haematuria; haema- a resistance to the usual antibiotics or
turia and severe crystalluria in an infection due In-house direct sediment examination fection. In other words, bacterial cystitis
to Proteus mirabilis. should be performed before sample may be diagnosed on the basis of pos- where a lack of compliance is highly
refrigeration. itive urinary cytology (e.g. microorga- probable. The use of fluoroquinolones

32 33
CANINE cystitis

• Reinfection is recurrence of a UTI


within 6 months of cessation of previous,

Figs. 2 & 4 © Salvador Cervantes


apparently successful treatment and
isolation of the same or a different mi-
croorganism. This suggests an underly-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


ing disease that predisposes the dog to
repeated infections. It should prompt a

© Rui Lemos Ferreira


careful search for any interference with
2 3 4
the innate defence mechanisms or ev-
Figures 2,3 & 4 - Cytology. Urinary sediment from dogs with cystitis. idence of immunosuppression (e.g. hy-
Fig 2. Note the phagocytosed coccoidal organisms inside neutrophils (culture result: Staphylo- peradrenocorticism, glucocorticoid use,
coccus spp.). diabetes).
Fig 3. Note the Bacilli (culture result: Klebsiella spp.) Image courtesy Dr. Eva Varela.
• Refractory infection is similar to a re-
Fig 4. French bulldog receiving corticosteroid therapy for atopy. The patient did not show UTI Figure 5 - Longitudinal sonogram of the urinary
signs (subclinical bacteriuria) but in culture, mixed populations of E. coli (bacilli) and lapse except that it is characterized by bladder in a dog showing moderate, diffuse, hy-
Streptococcus spp. (cocci in chains) were detected. The dog was not castrated and 3 persistently positive results using cul- poechoic, thickening of the bladder wall. Urine
spermatozoids are seen. (Diff Quik® x1000). ture during treatment. culture was negative but Mycoplasma cynos
DNA was detected by PCR.

as a first choice for bacterial cystitis in verse effects in some patients, especially
dogs is not recommended as this may with prolonged therapy. If prolonged (>7
lead to the selection of a multi-resist- days) therapy is anticipated, baseline
ant strain of E.coli. Fluoroquinolones in Schirmer’s tear testing is recommended,
these cases should be used with cau- with periodic re-evaluation and owner
tion1,2,7. monitoring for ocular discharge. Avoid
n If a TMS combination is used, the cli- in dogs that may be sensitive to potential
nician should be concerned regarding adverse effects such as KCS, hepatopa-
idiosyncratic and immune-mediated ad- thy, hypersensitivity and skin eruptions9.

Difficulties and particularities


n For uncomplicated cases, a 7-day course n Treatment failure may occur in three
of treatment is usually enough (>80% situations9:
of cases) but for complicated cases, a • Relapse is recurrence of a UTI within
longer course of antibiotics is recom- 6 months of cessation of previous, ap-
mended (28 days). For complicated ca- parently successful treatment and iso-
ses, culture and sensitivity are essential lation of an indistinguishable organism
before starting treatment but also after from the one that was present previously, For uncomplicated and first-time cases, cytology and urinary pH may suffice. However, urinary
discontinuation to make sure infection which is presumably because of failure to culture is the only reliable tool to confirm or rule out a urinary tract infection.
has fully cleared. completely eliminate the pathogen.

2
34 35
Feline (bacterial) cystitis
Bacterial cystitis is an uncommon cause of Feline Lower Urinary Tract
Pathogen 2: Enterococcus species (Gram-positive)
Disease (FLUTD). In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
• The majority of bladder infections in cats are due to a single bacterial species. 1 = nil
Amoxicillinf 4 5 2 = weak
• If the cat has chronic kidney disease, see Bacterial urinary tract infection in cats with
DISEASE FACT SHEETS

DISEASE FACT SHEETS


3 = average
Amoxicillin+clavulanate f 4 5
CKD, p.44. 4 = good
Marbofloxacin / Enrofloxacin b 3-4 5 5 = excellent

Bacteria involved 1, 3, 4, 9, 11, 12


Nitrofurantoin c 5 4 Treatment
choice
Pradofloxacin e 5 3
1st line
Bacteria Prevalence Cefalexing 2 5
Cefovecind,g 2 5 2nd line
Escherichia coli 25-59%
Trimethoprim sulfonamidesa,g 4-5 4 Last resort
Enterococcus spp. Clindamycin g
2 3
10-43%
(E. faecalis most common) Excluded
for this
Staphylococcus spp. 8-20% indication

a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
Antibiotics that can be used 6,8,11,12,18,19,20
testing is recommended if use > 3 weeks14.
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Nitrofurantoin is a human preparation useful in multi-drug resistant UTIs; use should be guided by culture and
Only if the use of antibiotics is justified: sensitivity testing and by cascade guidelines.
d Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
Pathogen 1: Escherichia coli (Gram-negative) sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
not possible.
In vitro Tissue Treatment Sensitivity e Pradofloxacin
is a last resort choice due to its very extended spectrum of activity and should only be used if a
Antibiotics that can be used and distribution narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
sensitivity distribution choice
1 = nil f Use of a ß-lactamase inhibitor (clavulanate) is not usually required for treatment of Enterococcus spp. infections
Amoxicillin 3 5 2 = weak hence amoxicillin+clavulanate is designated as 2nd choice, however use may be a compromise to achieve patient/
4 4 3 = average owner compliance.
Trimethoprim sulfonamidesa
4 = good g Enterococcus spp. do not typically respond in vivo to cephalosporins, TMS or clindamycin due to inherent resistance
Amoxicillin+clavulanate 4 5 5 = excellent mechanisms; be aware when interpreting in vitro results that these antibiotics are not recommended for
Treatment treatment6.
Cefalexin 3 5
choice
Marbofloxacin / Enrofloxacin b 5 5
1st line
Nitrofurantoinc 4 4
Cefovecind 4 5 2nd line

Pradofloxacine 5 3
Last resort

Excluded
for this
indication

36 37
Feline (bacterial) cystitis

Therapeutic approach Treatment recommendations15,20


n Non-antibiotic treatment: Analgesia should be provided (e.g. buprenorphine
transmucosally; NSAID if normally hydrated and normal renal function) and treat-
Urine dipstick, cytology
ment of comorbid disease where appropriate.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


First choice antibiotic (empirical)
Gram-negative rod
Antibiotics that
Pathogen involved Dosage Duration of treatment
Amoxicillin+clavulanate, can be used
trimethoprim sulfonamides 10-15 mg/kg/24 SC
Amoxicillin+clavulanate 12.5-25 mg/kg/8-12h PO
Escherichia coli in7dogs
days
Culture and sensitivity Trimethoprim uncomplicated UTI
15 mg/kg/12h PO
Empirical treatment sulfonamidesa 28 days
while awaiting results Gram-positive cocci complicated UTI
Enterococcus spp. Amoxicillinf 11-15 mg/kg/8h PO

Amoxicillin
Second choice antibiotic (following culture and sensitivity testing)

Antibiotics that
Pathogen involved Dosage Duration of treatment
Results of culture and sensitivity can be used
De-escalate if possible, adapt if necessary Amoxicillin 10-15 mg/kg/8h PO

Cefalexin 15-30 mg/kg/12h PO

Marbofloxacin 2 mg/kg/24h PO
E. coli Enterococcus spp. Escherichia coli Enrofloxacin b 5 mg/kg/24h PO
Amoxicillin ± clavulanate, 7 days
Nitrofurantoinc 4.4-5 mg/kg/8h PO
Amoxicillin uncomplicated UTI
trimethoprim sulfonamides
8 mg/kg SC for 14d 28 days
Cefovecind (for complicated UTIs complicated UTI
repeat dose after 14d)
Cefalexin,
Amoxicillin+clavulanate, Amoxicillin+clavulanatef 12.5-25 mg/kg/8-12h PO
marbofloxacin, enrofloxacin,
marbofloxacin, enrofloxacin,
nitrofurantoin (MDR UTI), Marbofloxacin 2 mg/kg/24h PO
nitrofurantoin (MDR UTI)
cefovecin Enterococcus spp.
Enrofloxacin b 5 mg/kg/24h PO

Nitrofurantoinc 4.4-5 mg/kg/8h PO


Pradofloxacin Pradofloxacin
For footnotes, see p. 37.

38 39
Feline (bacterial) cystitis

• Complicated UTI: infection in cats of clinical or cytological signs of infec-


Diagnostic approach with structural or functional urogenital tion20; significance not fully understood
n Bacterial cystitis is an uncommon n Diagnosis requires localisation of
tract abnormalities, immunosuppres- and currently treatment is warranted
cause of feline lower urinary tract dis- signs to the lower urinary tract, iden- sion or comorbid disease that predis- only in very specific circumstances e.g.
ease (FLUTD); sterile idiopathic cystitis tification of bacteria on urine cytology, poses to UTI or recurrent episodes (> 3 concurrent kidney disease, where the
DISEASE FACT SHEETS

DISEASE FACT SHEETS


is the cause of approximately 60% of culture (quantitative) & sensitivity and in 12 month period); treatment 28 days. risk of ascending infection could be
cystitis cases and is a primary exclusion exclusion of other causes of FLUTD. • Subclinical bacteriuria: identification of increased (N.B. this lacks an evidence
that does not warrant antibiotic treat- bacteria on urine culture in the absence base).
n Presenting signs: dysuria, stranguria,
ment5. pollakuria, haematuria, periuria, vocali-
n Predispositions: age, sex (more com- sation, increased perineal grooming, in- Urine samples for bacterial culture and sensitivity testing
mon in mature-geriatric female cats), continence, agitation and inappetence. should be refrigerated as soon as possible and processed at a
comorbidity (e.g. diabetes mellitus, Collapse and shock may be associated microbiology lab within 24 h to prevent false positives and false
CKD, hyperthyroidism), use of an in- with urethral obstruction (male cats). negatives. In-house direct sediment examination should be performed
dwelling urethral catheter, perineal before sample refrigeration.
n Clinical examination: caudal abdomi-
urethrostomy, immunocompromise and
nal discomfort, small or empty bladder,
neurogenic bladder.
pyrexia and dehydration. Urethral ob-
n The presenting signs are non-specific struction may result in a distended pain-
and may be seen with other sterile ful bladder, collapse, pallor, tachycardia
causes of FLUTD e.g. idiopathic cystitis or bradycardia (secondary to hyperkalae-
and urolithiasis. mia), hypothermia and poor peripheral
pulses.
n Urinalysis
• Biochemistry (dipstick): proteinuria (mild);
leukocyte readings are unreliable.
• Cytology: pyuria, haematuria, bacte-
riuria; Gram staining.
• Culture and sensitivity: on cystocen-
tesis samples (or via aseptically placed
urinary catheter); culture of free-catch
© Angie Hibbert

samples is only useful if negative (to ex-

© Salvador Cervantes
clude urinary tract infection - UTI).
n Classificationof UTIs
Double contrast cystogram revealing a diffusely
• Simple uncomplicated UTI: sporadic
thickened bladder wall in a male cat presenting infection in an otherwise healthy cat
with FLUTD. Final diagnosis: sterile idiopathic with normal urinary tract anatomy and
cystitis. Cystocentesis is the preferred sampling technique for culture and sensitivity testing.
function; treatment 7 days.

40 41
Feline (bacterial) cystitis

Reasoning Difficulties and particularities


n Urine cytology and culture are n Recurrence or failure to resolve clin- the catheter is in-situ is not recom-
strongly recommended for selection ical signs is justification for further in- mended, due to the risk of development
of effective first line antibiotics due to vestigation if the initial antibiotic choice of resistant UTI20. Culture of urine by
DISEASE FACT SHEETS

DISEASE FACT SHEETS


inherent microbial resistance patterns was appropriate and was administered cystocentesis following removal of the
and regional resistance profiles e.g. effectively. A search for underlying catheter is indicated only when lower
Enterococci spp. are typically resistant causes or predispositions should be urinary tract signs persist and in male
to cephalosporins (including cefovecin) performed (including full urinalysis, cats where the risk of urethral obstruc-
and TMS in vivo6. haematology, serum biochemistry, T4, tion due to spasm is higher. Culture of
FeLV/FIV serology, urinary tract imaging the removed urinary catheter tip is not

© Angie Hibbert
n Cytology can be used to guide an em-
pirical treatment pending culture and including contrast studies). Prevalence reliably predictive7.
sensitivity results: of UTI in association with CKD is 17- n For polymicrobial infections, one or
- Gram-negative bacteria: amoxicillin ± 30%, diabetes mellitus 11-13%, hyper- two antimicrobials may be required
clavulanate. thyroidism 12%1,2,22. based on sensitivity profiles. Anecdotal-
Urine cytology: neutrophils (degenerate) and
- Gram-positive bacteria: amoxicillin10. bacilli (intracellular and extracellular) in a cat n Bacterial cystitis associated with an ly, Enterococcus faecalis infection may
n Choice of antibiotic may be a compro- diagnosed with a bacterial urinary tract infection indwelling urinary catheter may not resolve without specific antimicrobial
(x1000 magnification, modified Wright’s stain). resolve until the catheter is removed. therapy when other bacteria are treated
mise between ideal drug vs. owner ability
to medicate with a specific preparation, Prophylactic antibiotic treatment whilst effectively20.
such as: response. Remember that the use of a
- Trimethoprim sulfonamide is often ß-lactamase inhibitor (clavulanate) is
problematic to administer due to the not usually required for treatment of
bitter taste of the medication. Enterococcus spp. infections. Typically
- Amoxicillin is ideally recommended 8 amoxicillin will suffice and is preferred
hourly (product instructions may indi- due to a narrower spectrum of activity (if
cate 12 hourly). compliance can be achieved).
- Cefovecin has a duration of action that n For complicated UTIs urine culture
is longer than required for simple UTIs; should be performed:
reserve for when oral medication is im- - 5-7 days following the start of treatment
possible. to assess efficacy,
See also recommendation R.2. - 5-7 days after completion of treatment
n When a simple uncomplicated UTI is
course (Note: with cefovecin, sampling
considered likely and urine culture is should be delayed to 21 days after the
not performed (e.g. impossible to obtain last dose20).
sample due to small bladder size, finan- n Nitrofurantoin is a human prepara-
cial constraints), treatment with amox- tion useful in multi-drug resistant UTIs.
icillin+clavulanate is a reasonable first Its use should be guided by culture and
choice13 and resolution of clinical signs sensitivity testing and by cascade guide-
can be taken as evidence of a positive lines.

2
42 43
Bacterial urinary tract
infection in cats with CKD
Pathogen 2: Enterococcus spp. (Gram-positive) Sensitivity
and distribution
Bacteria involved 1, 6, 12
Antibiotics that can be used
In vitro Tissue
sensitivity distribution
Treatment
choice
1 = nil
2 = weak
3 = average
Amoxicillin 4 5
Bacteria Prevalence 4 = good
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Amoxicillin + clavulanate f 4 5 5 = excellent
Treatment
Escherichia coli 59-71% Marbofloxacin / Enrofloxacinb 3-4 5 choice
Pradofloxacin d 5 3
Enterococcus spp. 1st line
6-15%
(E.faecalis) Cefalexine 2 5
Cefovecinc,e 2 5 2nd line

Antibiotics that can be used 2, 3, 4, 5, 9, 10, 11, 13


Trimethoprim sulfonamidesa,e 4-5 4 Last resort
Clindamycin e 2 3
Antibiotics that can be used based on culture and sensitivity results: Excluded
for this
indication
Pathogen 1: Escherichia coli (Gram-negative)
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
sensitivity distribution choice
1 = nil testing is recommended if use > 3 weeks7.
Amoxicillin 3 5 2 = weak
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
Amoxicillin + clavulanate 4 5 3 = average
4 = good sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
Trimethoprim sulfonamides a
4 4 5 = excellent possible.
d Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
Cefalexin 3 5 Treatment
choice narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
e Enterococcus spp. do not typically respond in vivo to cephalosporins, TMS or clindamycin due to inherent resistance
Marbofloxacin / Enrofloxacin b
5 5
1st line mechanisms; be aware when interpreting in vitro results that these antibiotics are not recommended for treatment2.
Cefovecinc 4 5 f Use of a ß-lactamase inhibitor (clavulanate) is not usually required for treatment of Enterococcus spp. infections
hence amoxicillin+clavulanate is designated as 2nd choice, however its use may be a compromise to achieve
Pradofloxacind 5 3 2nd line patient/owner compliance.

For footnotes, see next page. Last resort

Excluded
for this
indication

44 45
Bacterial urinary tract infection
in cats with CKD

Therapeutic approach

Urine dipstick, cytology


DISEASE FACT SHEETS

DISEASE FACT SHEETS


Gram-negative rod
(suspicion of Escherichia coli )

© Angie Hibbert
Amoxicillin ± clavulanate,
Culture and sensitivity trimethoprim sulfonamides
Empirical treatment
while awaiting results
Figure 1 - Renal ultrasound demonstrating cortex hyperechogenicity and mild pelvic dilation in a
Gram-positive cocci cat with pyelonephritis, causing an exacerbation of pre-existing CKD.
(suspicion of Enterococcus spp.)

Amoxicillin
Treatment recommendations
n In addition to on-going management assisted feeding if inappetent. Initial
Results of culture and sensitivity for CKD, analgesia should be provided treatment with intravenous antibiotic
De-escalate if possible, adapt if necessary if lower or acute upper urinary tract preparations is recommended in inap-
signs (e.g. buprenorphine) and any flu- petent +/- dehydrated patients, with a
id/electrolyte derangements should be transition to oral therapy once the cat is
E. coli Enterococcus spp. addressed. Consider nutritional support eating and fully hydrated.
e.g. anti-emetics, appetite stimulants or
Amoxicillin ± clavulanate,
Amoxicillin First choice antibiotic
trimethoprim sulfonamides
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used

Cefalexin, marbofloxacin, Amoxicillin + clavulanate, 10-25 mg/kg/8h IV 10-15 mg/kg/24 SC


Amoxicillin in dogs
enrofloxacin, cefovecin marbofloxacin, enrofloxacin 10-15 mg/kg/8h PO
10 mg/kg/8h IV
Escherichia coli Amoxicillin + clavulanate
12.5-25 mg/kg/8-12h PO 28 days
Trimethoprim complicated UTI
Pradofloxacin Pradofloxacin 15 mg/kg/12h PO
sulfonamidesa
10-25 mg/kg/8h IV
Enterococcus spp. Amoxicillin
10-15 mg/kg/8h PO
For footnotes, see p.45.

46 47
Bacterial urinary tract infection
in cats with CKD

Second choice antibiotic (with culture and sensitivity testing)8,11 acute pyelonephritis. for neoplasia, cystoliths (uroliths less
Dosage • Abdominal ultrasound to assess for commonly associated with UTI com-
Antibiotics that
Pathogen involved Consider adjustment for Duration of treatment upper urinary tract involvement (see pared to dogs).
can be used Stage 3&4 IRIS
Pyelonephritis, p.52), evaluate bladder
Cefalexin 15-30 mg/kg/12h PO 10-15 mg/kg/24 SC
DISEASE FACT SHEETS

DISEASE FACT SHEETS


in dogs
Marbofloxacin 2 mg/kg/24h IV, SC, PO

Escherichia coli Enrofloxacin b 5 mg/kg/24h SC, PO


Reasoning
n Urine cytology and culture are strongly efficacious and 5-7 days after comple-
8 mg/kg single dose SC 28 days
Cefovecinc recommended for selection of effective tion of course (for cefovecin, sample 21
(14d)
complicated UTI
20 mg/kg/8h IV first-line antibiotics due to inherent mi- days after the last dose was adminis-
f
Amoxicillin + clavulanate crobial resistance patterns and regional tered)11.
12.5-25 mg/kg/8-12h PO
Enterococcus spp. Marbofloxacin 2 mg/kg/24h IV, SC, PO
resistance profiles e.g. Enterococci spp. n Antibiotics excreted via the urinary
are typically resistant to cephalosporins tract will achieve high therapeutic con-
Enrofloxacinb 5 mg/kg/24h SC, PO (including cefovecin) and TMS in vivo. centrations at the site of infection; how-
For footnotes, see p.45. n Amoxicillin or amoxicillin+clavulanate ever, reduced GFR may result in drug
Culture and sensitivity testing should be performed to select the most appropriate are reasonable first-line empirical choices accumulation.
antibiotic and hence reduce the potential for further irreversible damage to the kidney. pending microbiological results; de-es- n Consider dose adjustment (i.e. in-
calate to narrower spectrum where creasing interval or reducing dose) in
possible. IRIS Stages 3 & 4.
Diagnostic approach n Treat as a complicated UTI for 28 n Aminoglycosides, nitrofurantoin and
n Bacterial UTI has been reported in leukocyte readings are unreliable days with culture 5-7 days after starting tetracyclines (except doxycycline) are
17-30% cats with CKD1,6,12 . Commonly - cytology: pyuria, haematuria, bacte- treatment to check chosen antibiotic is contraindicated.
UTI is an incidental finding or there are riuria; Gram staining
vague signs of illness (e.g. weight loss,
- culture and sensitivity (quantitative)
lethargy, reduced appetite); signs of
on cystocentesis samples (or via asep- Difficulties and particularities
cystitis (e.g. pollakuria, dysuria, stran-
tically placed urinary catheter); culture n Most of the cats reported with positive treatment, e.g. what is the real risk of
guria) or pyelonephritis (acute, chronic;
of free-catch samples is only useful to urine cultures and CKD have had occult exacerbation of renal function by an oc-
see Pyelonephritis, p.52) are infrequent.
exclude UTI. infections6,12. The significance of positive cult UTI or asymptomatic bacteriuria,
n Any deterioration in azotaemia, iden-
• Reassessment of serum biochemistry culture in this scenario is unknown al- how effective is antimicrobial treat-
tification of an active urine sediment or
to assess for deterioration in azotaemia, though the identification of pyuria sug- ment in fully resolving infections, how
pyrexia warrants investigation for bac-
hyperphosphataemia, inflammation (hy- gests a local reactive immune response. long should treatment courses be and
terial UTI, as a potential exacerbating
perglobulinaemia), electrolyte and acid One small study found no effect of oc- should screening cultures ever be per-
factor affecting renal function.
base disturbances (especially if upper cult UTI upon survival in cats with CKD, formed without cytological evidence of
n Evaluation urinary tract involvement is suspected). however cats received treatment12. Fur- infection?
• Urinalysis • Haematology: mild non-regenerative ther investigation is needed to answer n Increasing age and female gender are
- biochemistry (dipstick): proteinuria anaemia (CKD; acute inflammation), questions regarding monitoring and risk factors12.
(mild), +/- glycosuria, haemoglobinuria; neutrophilia (+/-left shift) in cases with

48 49
Bacterial urinary tract infection
in cats with CKD

Short case study including table of biochemistry


A 14-year-old male neutered DSH was diagnosed with bacterial urinary tract in-
fection following a one-year history of CKD. He presented with a single pyrexic
episode and three-month history of lethargy, increased PU/PD and inappetence.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Urinalysis revealed pyuria, haematuria and mild proteinuria. Treatment with
amoxicillin+clavulanate was initiated. A negative bacterial culture was returned
(likely due to prior antibiosis) however a marked clinical and biochemical response
was seen to antibiotic therapy. Diagnosis: bacterial pyelonephritis secondary to
chronic kidney disease.
Serum biochemistry results:

Day 1 Day 4 Day 28 4 months Ref range

Receiving treatment with Post


amoxicillin + clavulanate treatment
Urea
60 35.3 32 32 6.5-10.5
(mmol/l)
Creatinine
817 611 374 378 133-175
(μmol/l)
Phosphate
4.06 2.5 1.89 3.4 0.95-1.55
(mmol/l)
Globulin
64.6 - 48.2 49.0 21-51
(g/l)

Urine cytology and culture are


strongly recommended for selec-
tion of effective first-line antibiotics
due to inherent microbial resistance
patterns and regional resistance
profiles.

50 51
Pyelonephritis
Pathogen 3: Enterococcus spp.

Bacteria involved Antibiotics that can be used


In vitro Tissue
sensitivity distribution
Treatment
choice
Penicillin G / Ampicillin 4-5 4
Bacteria Prevalence
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Penicillin G + Gentamicin e,f 4-5 4
Escherichia coli ++++ (> 60 %) For footnotes, see at the end of the chapter.

Enterococcus spp. / Streptococcus spp. ++ (15 to 40 %)

Staphylococcus spp. + (< 10-20 %)


Therapeutic approach
Proteus spp. + (< 10-20 %)
Culture and sensitivity
Note: In feline CKD, the prevalence of chronic pyelonephritis has been estimated at 9.5–42%8. In dogs, in a recent
study11, of the 1,028 incidents of UTI in dogs, 363 (35.3%) were classified as uncomplicated and 665/1028 (64.7%) as
complicated. Of the complicated UTIs, 51/665 (7.7%) of dogs had pyelonephritis.

Empirical treatment while


Amoxicillin+clavulanate,
Antibiotics that can be used awaiting results or pending
trimethoprim sulfonamides
referral consultation
Antibiotics that can be used while awaiting C&AST results (if the use of antibiotics
is justified):
Pathogen 1: Escherichia coli
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Amoxicillin + clavulanate 4 5 2 = weak Results of culture and sensitivity
Trimethoprim sulfonamides a 4 5 3 = average De-escalate if possible, adapt if necessary
4 = good
Marbofloxacinb / Enrofloxacinb,c 4-5 5 5 = excellent
Treatment
choice
Ampicillin, penicilin, amoxicillin ± clavulanate,
Pathogen 2: Streptococcus spp. trimethoprim sulfonamides
In vitro Tissue Treatment 1st line
Antibiotics that can be used
sensitivity distribution choice
2nd line
Penicillin G / Ampicillin 4-5 4 Cefalexin, cefadroxil, marbofloxacin, enrofloxacin
Cefalexin 5 4 Last resort
Cefovecind 5 4
Excluded
For footnotes, see at the end of the chapter. for this Cefovecin, gentamicin
indication

52 53
Pyelonephritis

Treatment recommendations Diagnostic approach


First choice antibiotic n Dogs and cats with acute pyelone- urine sample by cystocentesis because
phritis of bacterial origin tend to pres- ascending urinary tract infection (UTI) is
Antibiotics that ent with a variable clinical picture: fever, one of the causes. Definitive diagnosis
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Pathogen involved Dosage Duration of treatment
can be used depression, anorexia, gastrointestinal requires urine obtained by percutane-
Amoxicillin+clavulanate 12.5–25 mg/kg/8h PO 10-15 mg/kg/24 SC signs (e.g. vomiting, renal pain) and leu- ous ultrasound-guided pyelocentesis.
Escherichia coli in dogs cocytosis. Pyelonephritis may be com-
Trimethoprim n Medical conditions that frequently
15 mg/kg/12h PO plicated by bacteraemia and urosepsis
sulfonamidesa predispose dogs to a UTI are diabetes
or progress to chronicity.
Penicillin G sodium mellitus, hyperadrenocorticism, exoge-
15-25 mg/kg/4-6h IV/IM 4-6 weeks It is essential to determine if a uri-
Penicillin G nary obstruction is associated. If yes, it nous steroid administration, renal fail-
Enterococcus spp. Penicillin G procaine
Streptococcus spp. 30 mg/kg/24h SC should be treated accordingly as it may ure, urethral catheterization, urinary
be life-threatening. Consider referral if retention, uroliths and urinary tract
20-50 mg/kg/6-8h
Ampicillin you have any doubt about the diagnosis. neoplasia. UTI including pyelonephritis
IV/IM/SC
n The clinical diagnosis of pyelonephri- is one of the common complications
Second choice antibiotic (with culture and sensitivity testing) tis is often presumptive based on results arising in cats associated with diseas-
of complete blood cell counts, serum es such as hyperthyroidism, diabetes
Antibiotics that chemistry profile, urinalysis, quantita- mellitus and chronic kidney disease. Af-
Pathogen involved Dosage Duration of treatment
can be used
tive urine culture and ultrasound (e.g. fected cats may or may not demonstrate
2 mg/kg/24h PO dilated renal pelvis). Always start with a clinical signs associated with the infection.
Marbofloxacinb
Escherichia coli (dogs and cats)
Enrofloxacinb,c 5 mg/kg/24h PO (dogs)
Ampicillin
Reasoning
Ampicillin 20-50 mg/kg/6-8h IV/ n Initial treatment should be made with
IM/SC
Enterococcus spp. + +
antimicrobial drugs known to have local
4-6 weeks or regional efficacy against Gram-nega-
Gentamicin
Gentamicin e,f
5-10 mg/kg/24h IM/SC tive Enterobacteriaceae10.
15-30 mg/kg/12h (PO) n Always perform urine cytology and
Cefalexin
or 24h (IM/SC) urine culture. When treating a UTI,
Streptococcus spp. 8 mg/kg single dose SC the clinical efficacy of an antibiotic is

© Rui Lemos Ferreira


Cefovecind (can be repeated once expected if its urine concentration is
after 7–14 d) maintained at 4 X above the MIC of the
For footnotes, see at the end of the chapter. pathogen between doses9. However, in
pyelonephritis, a deep tissue infection
needs to be treated. The interpretation
of susceptibility data should therefore be Figure 1 - Hydronephrosis in a dog with chronic
based on antimicrobial breakpoints for pyelonephritis.
serum rather than urine concentrations9.

54 55
Pyelonephritis

n Monitoring therapy is essential. The tion of treatment10. In vitro susceptibility


potential severity of the disease and results should guide antibiotic choice. Table 1 - Major clinical diagnostic features of upper urinary tract infection
the long treatment duration requires Treatment of 4–6 weeks is often recom- Acute pyelonephritis Chronic pyelonephritis
urinalysis (and/or cytology) and culture mended, as is consultation and hospi- - Fever, renal pain - Polydipsia/polyuria
1 week from the start and after cessa- talization with a specialist10. - Leucocytosis (neutrophilia) - Asymptomatic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


- Leucocyturia (pyuria) - Signs of chronic kidney disease
- Azotaemia, acidaemia - Azotaemia
Difficulties and particularities - Ultrasound imaging: dilated renal - Ultrasound imaging: dilated renal
n Recurrent pyelonephritis may be pelvis and retroperitoneal steatitis pelvis (without cause of obstruction)
asymptomatic9. Unresolved chronic py- - May be associated with lower urinary
elonephritis may lead to chronic kidney tract infection signs
disease. Therefore, diagnostic follow-up
is important to document resolution of
the pyelonephritis. Resolution is unlike-
ly in dogs and cats with nephroliths, un-
less they are removed.
n Antibiotics used should not be ne-
phrotoxic. High serum and urinary anti-
biotic concentrations do not necessarily

© Rui Lemos Ferreira


ensure high tissue concentrations in the
renal medulla. Treatment of chronic py-
elonephritis may be difficult to achieve.
Aminoglycosides should be avoided. Tri-
methoprim sulfonamide combinations
can cause significant adverse effects Figure 2 - Longitudinal image of a kidney in a
(keratoconjunctivitis sicca, blood dy- dog with pyelonephritis due to Mycoplasma UTI.
scrasias and polyarthritis).
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks6.
b Avoid use in growing dogs of large breeds.
c In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
d Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
not possible.
e Only for high-level gentamicin susceptible strains of Enterococcus spp.1,7
f Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/ education/prevention.html).

56 57
Canine prostatitis

Therapeutic approach
Bacteria involved
Cytology
Bacteria Prevalence
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Escherichia coli ++ (15 to 40%)

Staphylococcus spp. ++ (15 to 40%) Culture and sensitivity Trimethoprim


Empirical treatment sulfonamides
Streptococcus canis + (<10-20%)
while awaiting results

Antibiotics that can be used


Only if the use of antibiotics is justified.
ß-lactams should never be used due to their inability to cross the blood/
prostate barrier.
Pathogen 1: Escherichia coli Results of culture and sensitivity
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Trimethoprim sulfonamidesa 4 5 2 = weak
3 = average Escherichia coli Staphylococcus spp.
b
Marbofloxacin / Enrofloxacin b 4 5
4 = good (Gram-negative rod) (Gram-positive cocci)
Pradofloxacinb,c 4 5 5 = excellent
Chloramphenicol 4 5 Treatment Trimethoprim sulfonamides, Trimethoprim sulfonamides,
choice
Amoxicillin + clavulanate 3 1 marbofloxacin, enrofloxacin marbofloxacin, enrofloxacin
1st line
Cefalexin 3 1
2nd line Chloramphenicol, Chloramphenicol,
Pathogen 2: Staphylococcus spp.
pradofloxacin pradofloxacin
In vitro Tissue Treatment Last resort
Antibiotics that can be used
sensitivity distribution choice
Excluded
Trimethoprim sulfonamidesa 4 5 for this
indication
Marbofloxacinb/ Enrofloxacinb 4 5
Pradofloxacinb,c 5 5
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
Chloramphenicol 4 5
testing is recommended if use > 3 weeks9.
Amoxicillin + clavulanate 5 1 b Avoid use in growing dogs of large breeds.
c Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only
Cefalexin 5 1
be used if a narrower spectrum antibiotic cannot be used (based on sensitivity testing results).

58 59
Canine prostatitis

Treatment recommendations
First choice antibiotic
Antibiotics that
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Pathogen involved Dosage Duration of treatment
can be used
10-153-4
mg/kg/24
weeks SC

© Salvador Cervantes
Trimethoprim in dogs
(acute prostatitis)
Escherichia coli
15 mg/kg/12h PO
Staphylococcus spp. sulfonamidesa 6 weeks
(chronic prostatitis)

Second choice antibiotic (with culture and sensitivity testing)


Antibiotics that Figure 2 - Cytology. Prostatic massage sample from a dog with urothelial adenocarcinoma and
Pathogen involved Dosage Duration of treatment secondary prostatitis. Epithelial cells (normal and abnormal) are observed. Abnormal cells are
can be used
grouped as clusters and have a greater nucleus/cytoplasm ratio. Although infection or inflam-
10-153-4
mg/kg/24
weeks SC
Enrofloxacinb 5 mg/kg/24h PO mation was not observed on cytology, C&AST detected an infection by E.coli (Diff Quik®, 1000x).
Escherichia coli in dogs
(acute prostatitis)
Staphylococcus spp. 6 weeks
2 mg/kg/24h PO n A negative culture result of prostatic n If urine and prostatic liquid culture are
Marbofloxacinb (chronic prostatitis)
fluid will nearly always (89%) rule out negative it may be useful to take a biopsy
For footnotes, see on the previous page. an infection while a positive culture will for culture and sensitivity testing.
confirm bacterial infection in only half of
Diagnostic approach cases. Contamination during the sam-
n Prostatitis is an inflammation of the pling procedure is the most common
prostate gland, and may be acute or cause of false positive cultures6,8. Ul-
chronic. Although prostatic disorders trasonography is the method of choice
are very common in dogs, bacterial when investigating the prostate, imag-
prostatitis represents 30% of all cases, ing the size of the gland as well as the

© Salvador Cervantes
and is the second most common cause homogeneity of the parenchyma4,7.
of prostatic disease. n If concurrent cystitis is present, urine

n The signs associated with acute


culture has a good correlation with the
bacterial prostatitis include: lethargy, prostatic bacteria (>90%). Ultrasound
examination of the prostatic gland is al-
© Salvador Cervantes

weakness, fever, abdominal pain and,


in severe cases, sepsis and shock. In ways recommended to confirm or rule Figure 3 - Cytology: Urine sediment from a
chronic cases there is a decline in fer- out the presence of cysts or abscesses dog with prostatitis and secondary cystitis,
tility and recurring cystitis. Rectal pal- that may change the therapeutic ap- arrows show neutrophils. Transitional cells
proach. If cavities are detected during from bladder and numerous erythrocytes
pation is very painful in acute prostatitis. are also observed. Infection with Staphy-
Rectal massage may be used to obtain a the ultrasound exam a sample of liquid lococcus spp. was confirmed by urine and
sample (cytology, culture and sensitivi- Figure 1 - Prostatic massage3. should always be taken to differentiate prostatic culture.
ty) (Figure 1). an abscess from a cyst.

60 61
Canine prostatitis

Reasoning Difficulties and particularities


n In acute prostatitis, the blood–pros- penetration capacity of some antibiotics n Treatment of prostatitis is long, re-
tate barrier is broken1, resulting in an such as ß-lactams, they should not be lapses are frequent (particularly in
easy penetration of antibiotics and other used because therapeutic concentra- chronic cases) and known sequelae of
DISEASE FACT SHEETS

DISEASE FACT SHEETS


drugs into the gland. In chronic prostati- tions cannot be guaranteed during the bacterial prostatitis such as prostat-
tis, the blood–prostate barrier prevents treatment course. Once the infection ic abscesses may be seen (Figure 4).
the penetration of many drugs. Antibiotic is under control, castration (chemical Therefore, client compliance is vital.
choice is based on sensitivity testing or surgical) is recommended to help n As treatment is long, side effects of
and tissue distribution. Only weak al- control inflammation. If fertility is to be antibiotics may appear more frequently.
kaline antibiotics, with high pKa (acid maintained, osaterone (0.25-0.5 mg/
n If trimethoprim sulfonamides are
dissociation constant) and high lipid kg/24 h for 7 days every 6 months) may
recommended, check tear production
solubility, are able to diffuse into the help control benign prostatic hyperplasia.
regularly to avoid keratoconjunctivitis
prostatic parenchyma. The effectiveness Duration of treatment in acute cases is
sicca9.
of trimethoprim sulfonamides or clinda- 3-4 weeks, in chronic cases at least 6

© Salvador Cervantes
n In acute cases, depression may be
mycin has been proven, fluoroquinolo- weeks.
nes are also effective. followed by sepsis and shock. Hospital-
n In acute cases, clinical re-examina-
ization and aggressive therapy must be
n Culture and sensitivity testing of tion after 3-5 days should confirm an-
considered in all cases showing these
prostatic fluid (or urine if concurrent tibiotic efficacy. In chronic cases, a sec-
signs (Table 1).
bacterial cystitis is suspected) is re- ond culture should be performed 7-15 a b
quired because of the special anatom- days after the start of treatment. Figure 4 - Aspirates from a prostatic ab-
ical structure and chemical composition n In both cases, bacterial culture should
scess (a) and a prostatic cyst (b). Note the
of the prostatic gland. enhanced sedimentation on the left.
be performed at the end of treatment to
n Although inflammation increases the confirm full clearance of the infection.

Table 1 - Sepsis criteria in cats & dogs2,5.

Criteria Cats Dogs


Temperature (ºC) <37.7 or >39.4 ºC <37.7 or >38.8 ºC
Respiratory rate (bpm) >40 >20
Heart rate (bpm) <140 or >225 >120
Leukocytosis or leukopenia (103/μL) >19500 or <5000 >16000 or <6000

62 63
Epididymitis, orchitis
& balanoposthitis
Therapeutic approach (epididymitis, orchitis)
Bacteria involved
Balanoposthitis should be treated using local antiseptics.
Bacteria Prevalence When treating orchitis (with or without epididymitis), the final step is
DISEASE FACT SHEETS

DISEASE FACT SHEETS


surgical castration, since antibiotics rarely fully cure these infections.
Escherichia coli +++ (35 to 65 %)

Streptococcus spp. ++ (15 to 40 %)


Empirical treatment
Staphylococcus spp. ++ (15 to 40 %) (semen cytology, sample for culture)

Antibiotics that can be used


Pathogen 1: Escherichia coli Bacilli (assume) Cocci (assume)
Escherichia coli Staphylococcus / Streptococcus
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice Amoxicillin + clavulanate, Amoxicillin,
1 = nil
Trimethoprim sulfonamidesa 4 4 2 = weak trimethoprim sulfonamides trimethoprim sulfonamides
Amoxicillin 3 4 3 = average
4 = good
Amoxicillin + clavulanate 3 4 5 = excellent
Treatment
Culture and sensitivity
Cefalexin 4 4
choice
Marbofloxacinb / Enrofloxacinb,c 4 4
1st line
Pradofloxacin b,d 5 4
Escherichia coli Staphylococcus / Streptococcus
2nd line
Pathogen 2: Gram-positive cocci (Staphylococcus spp./Streptococcus spp.)
In vitro Tissue Treatment Last resort Amoxicillin, Amoxicillin,
Antibiotics that can be used trimethoprim sulfonamides trimethoprim sulfonamides
sensitivity distribution choice
Excluded
Trimethoprim sulfonamidesa 4 4 for this
indication
Amoxicillin 4 4
Amoxicillin + clavulanate,
Amoxicillin + clavulanate 5 4 Amoxicillin + clavulanate,
cefalexin,
marbofloxacin, enrofloxacin
Cefalexin 4 4 marbofloxacin, enrofloxacin
b
Marbofloxacin / Enrofloxacin b,c 4 4
Pradofloxacinb,d 5 4
For footnotes, see at the end of the chapter. Pradofloxacin Pradofloxacin

64 65
Epididymitis, orchitis & balanoposthitis

are pain, oedema and increase in size if only bacteria are detected without in-
Treatment recommendations of the structures affected (uni/bilateral flammatory cells, contamination should
n Non-antibiotic treatment: For balanoposthitis, the administration of a local anti- depending on the case) as well as hyper- be taken into consideration. Positive
septic suffices. Solutions of chlorhexidine or stabilized hypochlorous acid are ap- thermia and hypo/anorexia. The diagnosis sperm cultures must show at least 105
plied twice or three times on a daily basis until complete resolution (Table 1). is based on clinical signs and testicular bacteria/ml of sperm.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


ultrasonography and fine-needle aspi- n Balanoposthitis, inflammation of the
First choice antibiotic ration (FNA) of the testicle to rule out foreskin and glans, is a very common
other conditions (e.g. testicular torsion, condition in male dogs, usually caused
Antibiotics that
Pathogen involved Dosage Duration of treatment tumours)2. Sperm cytology and culture by the commensal flora of the area.
can be used
can confirm inflammation and infection, Clinical signs include inflammation
Escherichia coli Amoxicillin 10-15 mg/kg/8h although contamination from the ure- of the foreskin, pruritus or pain of the
Streptococcus spp. 14 days
Trimethoprim thral flora is quite common. If cytology preputial area and purulent discharge.
Staphylococcus spp. 15 mg/kg/12h
sulfonamidesa results show bacteria associated with Usually cytology allows differentiation
an inflammatory component then bac- between infection and normal preputial
Second choice antibiotic (with C&AST) terial orchitis is considered. However, discharge.
Antibiotics that
Pathogen involved
can be used
Dosage Duration of treatment
Reasoning
10-15 mg/kg/24 SC
Amoxicillin + clavulanate 12.5 -25 mg/kg/12h n For balanoposthitis, the selection of
Escherichia coli in dogs
the local antiseptic depends on patient
Streptococcus spp. Marbofloxacinb 2 mg/kg/24h 14 days
tolerance. Preferably use an antiseptic
Staphylococcus spp.
Enrofloxacinb,c 5 mg/kg/24h
that is well tolerated and has a long-
lasting effect (Table 1).

© Christelle Maurey
Streptococcus spp. n The treatment for orchitis/epididymitis
Cefalexin 15-30 mg/kg/12 h 14 days
Staphylococcus spp. consists of antibiotic treatment and cas-
For footnotes, see at the end of the chapter. tration. The blood-testis barrier hinders
good antibiotic tissue penetration. It
n Antibiotic therapy should be prolonged until castration can be performed and the may therefore be difficult to fully remove In case of balanoposthitis, the administration
clinician is totally sure the infection has been resolved. an infection in these areas without cas- of a local antiseptic suffices.
tration. Cytology and culture of sperm is

Diagnostic approach Table 1 - Disinfectants and their concentrations used as genital cleaners.
n Orchitis & Epididymitis, inflammation urinary system, traumatic (e.g. bites) Disinfectant Concentrations used
of testis and epididymis respectively, are and infection with Brucella canis. Brucella Chlorhexidine 0.05 - 0.5%
rare in dogs and extremely rare in cats. infections are rare, but the zoonotic po-
Povidone-Iodine 0.1 - 1
If orchitis is present, epididymitis is fre- tential is very serious. If orchitis is sus-
quently associated due to the anatomic pected, all precautions should be taken Stabilised hypochlorous acid 0.011%
close relation. The three most common to prevent human infection (e.g. gloves Benzalkonium chloride 0.006 - 0.012%
causes are ascending infection from the when handling samples)1. Clinical signs

66 67
Epididymitis, orchitis & balanoposthitis

useful but samples are not always easy


to obtain in patients experiencing pain.
Testicular FNA can be tried in these
cases although culture from these sam-
ples may be a challenge due to the low
DISEASE FACT SHEETS

DISEASE FACT SHEETS


number of bacteria.

© Salvador Cervantes
Once the patient has started antibiotic
treatment and infection is under control,
castration may be performed (usually
not before 48h).

Figure 1 - Ulcerative balanoposthitis and or-


chitis in a cat due to pain (licking) caused by
a chronic LUTD.

Difficulties and particularities


n Orchitis and epididymitis are rare n It is very important to explain to the
causes of testicular inflammation; tes- owner that without castration, infection
ticular torsion and tumours must first does not always clear up. This is due to
be ruled out. In cases without a defini- the blood-testis barrier preventing the
tive diagnosis, a biopsy of the tissue or antibiotics from reaching the infection
the entire testicles should be sent to a focus.
pathologist.

a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks3.
b Avoid use in growing dogs of large breeds.
c In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
d Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).

68 69
Metritis and pyometra

Therapeutic approach
• Ovariohysterectomy is the treatment of choice in any queen or bitch.
• In young, clinically stable breeding animals with an open cervix, catheterization
and lavage of the uterus and medical therapy with prostaglandins, dopamine ago- Culture and sensitivity
nists or progesterone receptor antagonists may be attempted. Amoxicillin ± clavulanate,
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Empirical treatment
trimethoprim sulfonamides
while awaiting results
Bacteria involved
Bacteria Prevalence

Escherichia coli ++++ (> 60 %) Results of culture and sensitivity


De-escalate if possible, adapt if necessary
Staphylococcus spp. + (< 10-20 %)

Streptococcus spp. + (< 10-20 %)

Escherichia coli Staphylococcus/Streptococcus


Antibiotics that can be used Amoxicillin, Amoxicillin,
Pathogen 1: Escherichia coli trimethoprim sulfonamides trimethoprim sulfonamides
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil Amoxicillin + clavulanate, Amoxicillin + clavulanate,
Amoxicillin 3 3 2 = weak cefalexin, cefalexin,
3 = average
Amoxicillin + clavulanate 3 3
4 = good
marbofloxacin, enrofloxacin marbofloxacin, enrofloxacin
Trimethoprim sulfonamides a 3 3 5 = excellent
Cefalexin 3 3 Treatment
choice
b
Marbofloxacin / Enrofloxacin b,c 4 4
1st line
Pathogen 2: Staphylococcus spp. / Streptococcus spp.
2nd line
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice Last resort
Trimethoprim sulfonamidesa 4 3
Excluded
Amoxicillin 5 3 for this
indication
Amoxicillin + clavulanate 5 3
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
Cefalexin 3 3 testing is recommended if use > 3 weeks3.
b Avoid use in growing dogs of large breeds.
Marbofloxacinb / Enrofloxacinb,c 4 4
c In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.

70 71
Metritis and pyometra

Treatment recommendations Diagnostic approach


First choice antibiotic n Endometritis and pyometra are com- lethargy, anorexia, fever, polydipsia and
mon diseases in the dog, but rare in the polyuria. Vaginal discharge is present
Antibiotics that
Pathogen involved Dosage Duration of treatment cat. Metritis can be caused by chronic in about 65 % of cases with pyometra.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


can be used
subclinical inflammation and bacterial Abdominal imaging can help identifying
Amoxicillin ± 10-25 mg/kg/12h PO,
Escherichia coli infection of the uterine wall leading to endometrial thickening and fluid-filled
clavulanate SC, IV
Staphylococcus spp. 2-3 weeks infertility in the bitch. distended uterine horns (Figure 1).
Streptococcus spp. Trimethoprim
15 mg/kg/12h PO, IV n In contrast, postpartum metritis re-
sulfonamidesa
fers to infection of the endometrium and
Second choice antibiotic (with culture and sensitivity testing) myometrium that develops within 3-7
days after whelping.
Antibiotics that

© Bianka Schulz
Pathogen involved Dosage Duration of treatment n Pyometra is an acute or chronic sup-
can be used
10-15 mg/kg/24 SC
purative inflammation of the uterine wall
Cefalexin 15-30 mg/kg/12h PO leading to accumulation of a neutro-
Escherichia coli in dogs
phil-rich exudate in the uterine lumen,
Staphylococcus spp. Marbofloxacinb 2 mg/kg/24h PO, SC, IV 2-3 weeks
Streptococcus spp.
which typically occurs 4-14 weeks after Figure 1 - Ultrasonographic image of pyometra
Enrofloxacinb,c 5 mg/kg/24h PO, SC an oestrous cycle. Typical clinical signs in a dog: note the enlarged, fluid-filled uterus.
of acute endometritis and pyometra are
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks3.

Reasoning
b Avoid use in growing dogs of large breeds.
c In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.

n Initial treatment should include fluid Streptococcus spp., Klebsiella spp. and
therapy and analgesia in systemically ill Proteus spp. have been recovered2,4.
© Thomas Chapalain

patients. n Recommendations for antibiotic therapy


n Bacterial culture and sensitivity test- are amoxicillin, amoxicillin+clavulanate,
ing should be performed in cases of trimethoprim sulfonamides or fluo-
acute and chronic endometrial disease. roquinolones. If sepsis is suspected,
Ideally, fluid for bacterial culture and antibiotic choice and dose should be
sensitivity testing is collected transcer- adapted to the situation (see Bacter-
vically from the uterus. If this is not aemia (sepsis), p.158). In sick and de-
possible, a cranial vaginal sample can hydrated animals antibiotics should be
be obtained by using a speculum and a given intravenously initially, if possible.
guarded swab. The most commonly iso- Many patients with acute uterine infec-
lated bacteria in dogs with endometritis tion are septic and need aggressive fluid
Complete ovariohysterectomy and pyometra are uropathogenic Es- management and additional stabilizing
is the preferred treatment. cherichia coli. In addition, vaginal com- measures. Complete ovariohysterec-
mensals such as Staphylococcus aureus, tomy is the preferred treatment in any

72 73
Metritis and pyometra

queen or bitch. In young, clinically stable medical therapy with prostaglandins,


breeding animals with an open cervix, dopamine agonists or progesterone re-
catheterization and lavage of the uterus and ceptor antagonists can be attempted.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Difficulties and particularities
n Antibiotic therapy is considered sup- resolution of vulvar discharge and re-
portive therapy in animals with endo- moval of all fluid from the uterine lumen
metritis and pyometra. It cannot substi- as determined by ultrasonography. Es-
tute manual or medical drainage of pus pecially in bitches and queens that are
and bacteria from the uterus or ovari- managed conservatively, close moni-
ohysterectomy. Severely sick animals toring of vaginal discharge, CBC, and
can have decreased kidney and liver abdominal ultrasound is necessary to
function due to sepsis and dehydration. evaluate the success of treatment.
Therefore, antibiotics should not have a n For non-breeding animals, ovariohyster-
nephrotoxic or hepatotoxic potential1. ectomy is the treatment of choice. Because
n In cases of acute post-partum metri- patients are often in poor condition for
tis, the chosen antibiotics should not surgery, they should be stabilized first
be toxic to the puppies (e.g. amoxicil- with intravenous fluids and antibiotics.
lin+clavulanate, cephalosporins), if they Antibiotic treatment should be given for
stay with the mother. With conservative at least 10-14 days. In animals with sepsis
treatment, antimicrobial therapy should and endotoxaemia, antibiotics should be
be continued for at least 14 days after given intravenously.

74 75
Vaginitis
Juvenile vaginitis rarely requires antibiotic treatment and usually resolves
spontaneously.
Therapeutic approach

Bacteria involved Culture and sensitivity


DISEASE FACT SHEETS

DISEASE FACT SHEETS


Bacteria Prevalence

Escherichia coli Staphylococcus / Streptococcus


Escherichia coli ++ (15 to 40 %)

Amoxicillin ± clavulanate,
Staphylococcus spp. ++ (15 to 40 %) Amoxicillin ± clavulanate
clindamycin
Streptococcus spp. ++ (15 to 40 %)

Cefalexin, Cefalexin,
marbofloxacin, enrofloxacin marbofloxacin, enrofloxacin
Antibiotics that can be used
Pathogen 1: Escherichia coli
Antibiotics that can be used
In vitro Tissue Treatment Sensitivity Treatment recommendations
sensitivity distribution choice and distribution
1 = nil First choice antibiotic
Amoxicillin 3 3 2 = weak
Amoxicillin + clavulanate 3 3 3 = average Antibiotics that
4 = good Pathogen involved Dosage Duration of treatment
can be used
Cefalexin 3 3 5 = excellent
Treatment
10-25 mg/kg/12h PO,
Marbofloxacina / Enrofloxacina,b 4 4 Amoxicillin
choice SC, IV
Escherichia coli
Amoxicillin + 12.5-25 mg/kg/12h PO,
Pathogen 2: Staphylococcus spp. / Streptococcus spp. 1st line
clavulanate SC, IV
2-3 weeks
In vitro Tissue Treatment Staphylococcus spp. 5.5-11 mg/kg/12h PO,
Antibiotics that can be used 2nd line Clindamycin
sensitivity distribution choice Streptococcus spp. IV
Amoxicillin 5 3 Last resort
Amoxicillin + clavulanate 5 3 Second choice antibiotic (with culture and sensitivity testing)
Excluded
Clindamycin 4 4 for this Antibiotics that
indication Pathogen involved Dosage Duration of treatment
can be used
Cefalexin 3 3
Cefalexin 15-30 mg/kg/12h PO 10-15 mg/kg/24 SC
Marbofloxacina / Enrofloxacina,b 4 4 in dogs
Escherichia coli
Staphylococcus spp. Marbofloxacina 2 mg/kg/24h PO, SC, IV 2-3 weeks
a Avoid use in growing dogs of large breeds.
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
Streptococcus spp.
Enrofloxacina,b 5 mg/kg/24h PO, SC

76 77
Vaginitis

spp., and Brucella canis1,2. Results of


Diagnostic approach bacterial culture need to be interpreted
n Vaginitis is more common in dogs with care, because of the existing phys-
than in cats. Canine vaginitis can be iological urogenital microflora. While
differentiated into juvenile vaginitis and the massive growth of a single organ-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


vaginitis in the adult bitch. Juvenile or ism probably indicates bacterial infec-
“puppy vaginitis” is a condition occur- tion, growth of several bacterial species

© Christelle Maurey
ring in healthy puppies from 6 weeks up most likely represents normal bacterial
to puberty that is thought to be caused commensals that do not need antibiotic
by an imbalance of the juvenile vaginal treatment. In cases of chronic bacterial
glandular epithelium. It is considered a infection, a course of treatment of two to
sterile inflammation and rarely requires three weeks has been suggested.
Figure 2 - Juvenile sterile vaginitis normally
antibiotic treatment. does not require antibiotic treatment; clini-
n Adult onset vaginitis can be caused by cal signs usually improve with maturity.

© Bianka Schulz
various underlying problems, and is fre-
quently accompanied by perivulvar and
vulvar dermatitis. Chronic vaginitis in Difficulties and particularities
adult bitches can be caused by primary
infectious organisms (canine herpesvi- Figure 1 - Endoscopic image of vaginitis in n In case of idiopathic adult-onset vag- authors. If treatment is requested, a
rus, Brucella canis) or overgrowth of an a dog. initis, treatment can be frustrating, combination protocol of tetracyclines or
atypical bacterial species if the normal because animals often show a relapse fluoroquinolones and aminoglycosides
vaginal flora is disturbed. Underlying focus on the identification of possible of clinical signs following discontinua- has been recommended.
causes include redundant dorsal and lat- underlying conditions and include blood tion of antibiotics. In these cases, oral n Although Mycoplasma spp. belong
eral vulvar folds, foreign bodies, urinary work, urinalysis (sample obtained by oestrogen replacement therapy can be to the normal vaginal microflora, cer-
tract infections (urethritis), vestibulitis cystocentesis) with culture and sensitiv- helpful in establishing normal vaginal tain virulent strains of the organism are
and vulvitis, conditions causing urinary ity, endoscopic vaginal examination, and mucosal integrity and to prevent chronic thought to be responsible for chronic
incontinence, urogenital neo-plasms vaginal cytology and culture. In addition, secondary bacterial infection. vaginitis and infertility in the bitch. For
and vaginal strictures, but can often screening for canine herpesvirus and n For genital infections with Brucella detection of Mycoplasma spp., special
be idiopathic. Primary work-up should Brucella canis may be indicated. canis, no treatment protocol has been culture media or PCR must be request-
shown to consistently achieve long- ed. Because the organism shows nat-
term cure. Due to the zoonotic po- ural resistance to ß-lactam antibiotics,
Reasoning tential of the disease, especially if doxycycline or fluoroquinolones are rec-
n Juvenile sterile vaginitis normally the results of culture and sensitivity test- owners are immunocompromised, eu- ommended for treatment.
does not require antibiotic treatment; ing. A vaginal sample can be obtained by thanasia of the pet is suggested by some
clinical signs usually improve with maturity. using a speculum and a guarded swab.
n In mature bitches, treatment should be The most commonly isolated bacteria
aimed at the underlying condition. Dogs in dogs with vaginitis are uropathogenic
with severe clinical disease should re- Escherichia coli, Streptococcus, Staphy-
ceive antibiotic treatment depending on lococcus, Mycoplasma spp., Pasteurella

78 79
Mastitis

Bacteria involved Therapeutic approach


Bacteria Prevalence and sensitivity
Culture and
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Escherichia coli ++ (15 to 40 %)

Staphylococcus spp. ++ (15 to 40 %) Escherichia coli Staphylococcus

Streptococcus spp. + (< 10-20 %) Amoxicillin ± clavulanate, Amoxicillin ± clavulanate,


trimethoprim sulfonamides trimethoprim sulfonamides

Antibiotics that can be used


Cefalexin, Cefalexin,
Pathogen 1: Escherichia coli marbofloxacin, enrofloxacin marbofloxacin, enrofloxacin
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Amoxicillin 3 3 2 = weak Treatment recommendations
Amoxicillin + clavulanate 3 3 3 = average
4 = good In nursing bitches and queens, only amoxicillin ± clavulanate and cefalexin should
Trimethoprim sulfonamidesa 4 4 Not if nursing 5 = excellent be used.
Cefalexin 3 3 Treatment
choice First choice antibiotic
Marbofloxacinb / Enrofloxacinb,c 4 4 Not if nursing
1st line Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Pathogen 2: Staphylococcus spp. 2 line
nd
Amoxicillin ± 10-25 mg/kg/12h PO,
In vitro Tissue Treatment Escherichia coli clavulanate SC, IV
Antibiotics that can be used Staphylococcus spp. 10-14 days
sensitivity distribution choice Last resort
Streptococcus spp. Trimethoprim 12.5-25 mg/kg/12h PO,
Amoxicillin 5 3 sulfonamidesa SC, IV
Excluded
Amoxicillin + clavulanate 5 3 for this
indication Second choice antibiotic (with culture and sensitivity testing)
Trimethoprim sulfonamidesa 4 4 Not if nursing
Cefalexin 3 3 Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Marbofloxacinb / Enrofloxacinb,c 4 4 Not if nursing
Cefalexin 15-30 mg/kg/12h PO 10-15 mg/kg/24 SC
Escherichia coli in dogs
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear Staphylococcus spp. Marbofloxacinb 2 mg/kg/24h PO, SC, IV 10-14 days
testing is recommended if use > 3 weeks2. Streptococcus spp.
b Avoid use in growing dogs of large breeds.
Enrofloxacinb,c 5 mg/kg/24h PO, SC
c In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.

80 81
Mastitis

must be taken with the selection of


Diagnostic approach antibiotics in these cases. While peni-
n Mastitis occurs more commonly in cillins and cephalosporins are usually
dogs than in cats. Septic inflammation well tolerated by the puppies, fluoro-
of the mammary gland can be caused quinolones, tetracyclines and amino-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


by ascending infection due to injuries glycosides should be avoided. If the
caused by the puppies or by haematoge- puppies stop feeding from the glands,
nous spread of bacteria and is common- manual stripping is recommended to
ly accompanied by systemic illness. This ensure adequate drainage. In addi-

© Thomas Chapalain
condition typically occurs post-partum; tion, warm compresses of the affected
sometimes also in pseudopregnant an- glands can be a supportive measure. Figure 3 - If the bitch is nursing, some an-
imals. Non-septic mastitis is caused tibiotics should be avoided because of their
by milk stasis (e.g. sudden weaning) undesirable effects on new-born animals.
leading to swelling and inflammation.
The affected glands become hot, swol-
Figure 1 - Septic mastitis typically occurs
len and painful and the milk can be
discoloured. A milk sample can be ob- post-partum. Difficulties and particularities
tained manually or by direct aspiration n If the dam or puppies appear severely diffusion of antibiotics depends on the
from the gland for cytology and culture in animals with septic mastitis, cytology sick, puppies should be removed from pH of the milk and lipid solubility of the
and sensitivity testing. While cytology of in animals with non-septic mastitis re- the mother and hand-reared. In cases of antibiotics. While weak alkaline antibi-
the milk usually shows a high number of veals few bacteria and a possible mild abscessed and necrotic glands, surgical otics such as clindamycin and erythro-
bacteria and degenerative neutrophils increase in neutrophils. debridement and in severe cases mas- mycin concentrate better in milk with an
tectomy may be necessary and puppies acid pH, amoxicillin + clavulanate and
must be separated. cephalosporins reach higher concentra-
Reasoning n Mastitis can be acute or chronic. With tions in milk with an alkaline pH.
severe inflammation in acute septic n In non-septic mastitis, there is no
n Escherichia coli, ß-haemolytic strep-
mastitis, most antibiotics easily pene- need for antibiotic therapy. This con-
tococci and staphylococci are the most
trate the blood-mammary barrier and dition is best treated with continuous
commonly detected pathogens in cases
reach high concentrations in the in- drainage of the gland (manual expres-
of septic mastitis1,3. While non-septic
flamed tissue. In more chronic cases, sion or continuous nursing).
mastitis is not an indication for antibiot-
ic therapy, animals with septic mastitis
require systemic antibiotic treatment.
Furthermore, analgesia and fluid ther-
apy might be indicated. Puppies should
be encouraged to continue nursing
in order to support drainage of the Figure 2 - In case of acute mastitis, most
glands and promote adequate nutrition- antibiotics easily penetrate the blood-mam-
al intake, as long as the glands are not mary barrier.
abscessed or necrotic. However, care

82 83
DISEASE FACT SHEETS

84
Respiratory tract

85

DISEASE FACT SHEETS


Canine rhinitis

Treatment recommendations
Bacteria involved
Culture and sensitivity testing is not justified in most cases of canine nasal disease,
Canine chronic rhinitis is not considered a primary bacterial disease, but antibiotic treatment of secondary bacterial infections can be necessary.
but a secondary bacterial infection following a primary nasal condition.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


There are no studies on prevalence rates of primary or secondary bacteria First choice antibiotic
associated with canine nasal disease.
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Amoxicillin + 12.5-25 mg/kg/12h PO,
Therapeutic approach Culture not clavulanate SC, IV
2-3 weeks
recommended 5 mg/kg/12h or
Doxycycline
10 mg/kg/24h PO
Empirical treatment
ONLY IF antibiotherapy is necessary Second choice antibiotic (without culture and sensitivity testing)
Antibiotics that
Pathogen involved Dosage Duration of treatment
Amoxicillin+clavulanate, can be used
doxycycline Marbofloxacina 2 mg/kg/24h PO, SC 10-15 mg/kg/24 SC
Culture not in dogs
2-3 weeks
recommended
Enrofloxacina 5 mg/kg/24h PO, SC

Marbofloxacin, enrofloxacin a Avoid use in growing dogs of large breeds.

Diagnostic approach
n Canine rhinitis is not considered a pri-
If insufficient improvement, mary bacterial disease but a secondary
consider culture and AST bacterial infection following a primary
of nasal biopsy or nasal flush nasal condition. According to retrospec-
tive studies, the most common underly-
ing problems are nasal neoplasia, lym-
phoplasmacytic rhinitis, nasal foreign

© Bianka Schulz
body, sinonasal aspergillosis or dental
problems (Figure 1)1,2,3.
n Work-up of nasal disease commonly
includes computed tomography, rhi-
noscopy (Figure 2) and histopathology Figure 1 - Dog with chronic purulent nasal
discharge. In this case, bacterial infection was
of nasal biopsies. Bacterial culture and secondary to chronic lymphoplasmacytic
sensitivity testing of nasal swabs or na- rhinitis.
sal discharge are not recommended as

86 87
Canine rhinitis

part of the work-up of canine nasal dis-


ease, because cultured bacteria most
likely represent the physiological micro-
flora of the upper respiratory tract and
cannot be differentiated from bacteria
DISEASE FACT SHEETS

DISEASE FACT SHEETS


that might be involved in infection. Bar-

© Bianka Schulz
tonella, Mycoplasma and Chlamydophi-
la species do not seem to play a role in
dogs with chronic lymphoplasmacytic
rhinitis or nasal neoplasia4.
Figure 2 - Diagnostic work-up of chronic
nasal disease includes rhinoscopic exami-
nation of the nasal cavity.

Reasoning
n Since canine chronic rhinitis is primarily respond rapidly to antibiotic treatment,
a non-infectious problem that can be although clinical signs often relapse
complicated by bacterial infection, after discontinuation of antibiotic treat-
treatment has to be directed primarily ment. Most dogs improve with antibiotic
towards the underlying problem. However, agents such as amoxicillin+clavulanate
in some case (e.g. chronic lymphoplas- or doxycycline (first choice) over two to
macytic rhinitis, nasal neoplasia), aeti- three weeks. Doxycycline might have an
ological treatment can be frustrating or additional beneficial effect in dogs with
even impossible and patients can bene- chronic rhinitis due to its anti-inflam-
fit from treatment of the secondary bac- matory properties. There are no studies
terial infection. Dogs with purulent nasal comparing the efficacy of different an-
discharge or neutrophilic inflammation tibiotics and optimal duration of treat-
on histopathology of nasal biopsies often ment in dogs with chronic rhinitis.

Difficulties and particularities


n Many cases of chronic nasal disease rhinoscopy is strongly recommended.
improve initially on antibiotic therapy but If cultures are considered, they should
relapse after discontinuation of antibi- be performed on nasal biopsies or nasal
otics or even while still under therapy, flush; however, there are no studies that
because the underlying problem is not prove the significance of this diagnostic
treated simultaneously. In case of chronic method in identification of significant
rhinitis, work-up including imaging and bacteria.

88 89
Canine tracheobronchitis

Therapeutic approach
Bacteria involved
Bacteria Prevalence Reported associations Empirical treatment
DISEASE FACT SHEETS

DISEASE FACT SHEETS


ONLY IF antibiotherapy is necessary
Bordetella bronchiseptica ++ (15 to 40 %) Frequently co-infections with
respiratory viruses (canine distemper
virus, canine adenovirus type 2, Amoxicillin+clavulanate,
Streptococcus spp. + (< 10-20 %)
canine parainfluenza virus, canine doxycycline
herpesvirus-1, canine respiratory
Mycoplasma cynos + (< 10-20 %) coronavirus, canine influenza).

Marbofloxacin, enrofloxacin
Antibiotics that can be used
Pathogen 1: Bordetella bronchiseptica
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
If insufficient improvement,
Amoxicillin + clavulanate 4 3 2 = weak perform tracheal or bronchial
Doxycycline 4 4
3 = average lavage, cytology and C&AST
4 = good
Trimethoprim sulfonamides a 3 4 5 = excellent
Treatment
Marbofloxacinb 4 5 choice
Enrofloxacin b 4 5
1st line
Pathogen 2: Streptococcus spp.
2nd line
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice Last resort

Amoxicillin 5 3
Excluded
Cefalexin 4 4 for this
indication
Doxycycline 3 4
Marbofloxacinb 3 5
Enrofloxacin b 3 5
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks3.
b Avoid use in growing dogs of large breeds.

90 91
Canine tracheobronchitis

respiratory coronavirus and canine in- mild and self-limiting clinical signs, dogs
Treatment recommendations fluenza virus as well as the bacterial infected with primary or secondary bac-
First choice antibiotic agents Streptococcus equi subspecies terial pathogens frequently show more
zooepidemicus and Mycoplasma cynos 2,4. severe signs and antibiotic therapy is
Antibiotics that
Pathogen involved Dosage Duration of treatment Co-infections with multiple viral and indicated in these cases. If dogs do not
DISEASE FACT SHEETS

DISEASE FACT SHEETS


can be used
bacterial pathogens are common in respond to empirical antibiotic therapy,
Amoxicillin + 12.5-25 mg/kg/12h PO,
dogs with CIRD6. tracheal or broncheo-alveolar lavage is
Bordetella clavulanate SC, IV
bronchiseptica 7-10 days, n While most dogs suffering from viral indicated to perform cytology, culture,
Doxycycline 10 mg/kg/24h PO until clinical and infections are thought to exhibit rather and sensitivity testing.
radiographic cure
Streptococcus spp. Amoxicillin 10-15 mg/kg/12h PO
Reasoning
Second choice antibiotic (with culture and sensitivity testing) n In cases of uncomplicated CIRD, if
Antibiotics that dogs are not febrile and show only mild
Pathogen involved Dosage Duration of treatment
can be used clinical signs, antibiotic therapy is not
Trimethoprim 15-30 mg/kg/12h PO, indicated and clinical disease is usual-
sulfonamidesa IV ly self-limiting within seven to ten days.
Bordetella In these cases, disease is most likely
bronchiseptica Marbofloxacinb 2 mg/kg/24h PO, SC
caused by respiratory viruses. If clinical
Enrofloxacinb 5 mg/kg/24h PO, SC signs do not improve or dogs are febrile,
7-10 days, anorexic and depressed, antibiotic ther-
Cefalexin 15-30 mg/kg/12h PO until clinical and apy is indicated.
radiographic cure
n For empirical therapy, amoxicillin+
Doxycycline 10 mg/kg/24h PO
Streptococcus spp. clavulanate or doxycycline can be used
Marbofloxacinb 2 mg/kg/24h PO, SC as first-line treatment. If Mycoplas-
ma spp. are suspected or diagnosed,
Enrofloxacinb 5 mg/kg/24h PO, SC doxycycline can be given as first-line

© Bianka Schulz
a Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
and fluoroquinolones as second-line
testing is recommended if use > 3 weeks3. treatment, since these organisms are
b Avoid use in growing dogs of large breeds.
naturally resistant to ß-lactam anti-
biotics. If dogs do not show significant
Diagnostic approach improvement following empirical an-
tibiotic therapy, cytology and culture
Figure 1 - Nebulization of a pug with acute
febrile tracheobronchitis to improve airway
n The so-called “Canine Infectious Res- adenovirus type 2, canine parainfluenza and sensitivity testing of tracheal or humidification.
piratory Disease” (CIRD) is a multi-fac- virus, canine herpesvirus-1, and Borde- broncheo-alveolar lavage fluid (BALF)
torial infection of the upper respiratory tella bronchiseptica were the common samples is recommended. Bordetella n In addition, supporting therapy such
tract caused by single or multiple viral pathogens associated with this disease bronchiseptica isolates have shown as nebulization (Figure 1), fluid therapy
and/or bacterial agents1. While tradi- complex, recent studies showed involve- varying degrees of resistance to doxycy- and mucolytic drugs can help to improve
tionally canine distemper virus, canine ment of new viral agents such as canine cline and aminopenicillins5. mucociliary clearance in dogs with CIRD.

92 93
Canine tracheobronchitis

Difficulties and particularities


n In cases of chronic coughing, uncom- missed with conventional culture.
plicated viral tracheobronchitis is unlike- n Not all antibiotics penetrate well into
ly and the dog’s case should be worked up the bronchial tree, which can also be a
DISEASE FACT SHEETS

DISEASE FACT SHEETS


for this clinical condition. Chronic coughing reason for treatment failure in bacterial
can have many different reasons, including bronchitis. Fluoroquinolones, trimeth-
underlying cardiac disease, chronic in- oprim sulfonamides and doxycycline
flammatory airway disease, airway col- can reach higher concentrations in the
lapse or neoplasia. bronchi than most ß-lactam antibiotics.
n Some bacteria such as Bordetella Although the optimal duration of anti-
bronchiseptica or Mycoplasma spp. also biotic therapy is unknown, treatment
have the potential to cause chronic infec- should be given at least until clinical
tion and should be identified by bacteri- signs disappear, which is usually after
al culture. Mycoplasmas require special seven to ten days.
culture media and might therefore be

If dogs do not show significant improvement following empirical antibiotic therapy, cytology and
culture and sensitivity testing of tracheal or broncheo-alveolar lavage fluid (BALF) sample is
recommended.

94 95
Feline rhinitis and
tracheobronchitis
Bacteria involved Antibiotics that can be used
Doxycyline is the empirical antibiotic of choice for upper and lower bacterial respi-
Acute rhinitis and tracheobronchitis
ratory infection.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Bacteria Prevalence Possible associations
Pathogen 1: Bordetella bronchiseptica
Prevalence is highly
Bordetella bronchiseptica variable depending on In vitro Tissue Treatment Sensitivity
Viral co-infections Antibiotics that can be used and distribution
background; highest sensitivity distribution choice
(see following pages) 1 = nil
Chlamydia felis prevalence is expected Doxycyclinec 5 5
Opportunistic secondary bacterial 2 = weak
(ocular and nasal disease) in group settings (e.g.in 3 = average
infection with commensal species. Amoxicillin + clavulanate 3-4 4
shelters and breeding 4 = good
Mycoplasma felis catteries with large Marbofloxacin 5 5 5 = excellent
numbers of cats) Treatment
Enrofloxacin a 5 5 choice
Pradofloxacinb 5 5
1st line
Chronic rhinitis 6,7,11,16
Pathogen 2: Pasteurella spp.
2nd line

Bacteria Prevalence Possible associations In vitro Tissue Treatment


Antibiotics that can be used
sensitivity distribution choice Last resort

Pasteurella spp. 13-32% Doxycyclinec 5 5


Excluded
Amoxicillin 5 4 for this
Staphylococcus spp. 13-30% indication
Prior viral infection Amoxicillin + clavulanatee 5 4
with feline herpes virus-1 (FHV)
Mycoplasma spp. 20-34% Marbofloxacin 5 5
and/or feline calicivirus (FCV);
FHV recrudescence possible. Enrofloxacina 5 5
Escherichia coli 5-40%
Pradofloxacin b 5 5
Streptococcus spp. 6-20%
Pathogen 3: Mycoplasma spp.
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice
Chronic bronchitis/asthma with complicating bacterial infection14,16 Doxycyclinec 5
Marbofloxacin 5
Bacteria Prevalence Not
Enrofloxacin a routinely 5
Mycoplasma spp. ++ (15%) available
Clindamycin 5

Pasteurella spp. 3-21% Pradofloxacin b 5


For footnotes, see at the end of the chapter.

96 97
Feline rhinitis and tracheobronchitis

Therapeutic approach Treatment recommendations


Non-antibiotic treatment may include: n Chronic rhinitis: nasal flushing un-
Upper respiratory tract signs n Acute rhinitis and tracheobronchitis: der anaesthesia, saline nebulisation or
Since < 10 days?
removal of the underlying cause in steam therapy, NSAIDs (if hydrated and
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Yes No
acute rhinitis where possible (e.g. for- adequate renal function), nutritional
eign body), fluid therapy to address de- support (as above), famcyclovir if acute
Acute disease Chronic disease hydration/electrolyte derangements if FHV recrudescence.
present, saline nebulisation or steam n Chronic bronchitis/asthma: anthel-
therapy, frequent cleaning of nares, mintic treatment to exclude concurrent
• Address any underlying illness, e.g. viral infection famcyclovir if acute FHV co-infection, Aleurostrongylus abstrusus infestation
• Supportive treatment usually suffices oxygen therapy if dyspnoeic due to con- in hunting cats (e.g. moxidectin/imida-
current bronchopneumonia, NSAIDs (if cloprid), bronchodilators (terbutaline
hydrated and adequate renal function), in acute scenario), glucocorticoids at
nutritional support (e.g. small portions anti-inflammatory doses (e.g. inhaled
Empirical treatment if severe
clinical signs
of warm strong smelling foods, mir- fluticasone, oral prednisolone), avoid-
(mucopurulent discharge, fever, lethargy, inappetence) tazapine, naso-oesophageal/oesopha- ance of airway irritants (e.g. smoke,
gostomy tube if severe signs). dust mites).

If no Diagnostic tests*:
Doxycycline
improvement cytology and C&AST First choice antibiotic (empirical or with culture and sensitivity testing)
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Bordetella
bronchiseptica
Pasteurella spp. Mycoplasma spp. Acute rhinitis & tracheobronchitis
with Bordetella bronchiseptica,
Doxycycline Doxycycline Doxycycline Mycoplasma spp. or secondary
bacterial infection: 7-10 days;
Chlamydia felis: 4 weeks
Amoxicillin + Bordetella
bronchiseptica, Chronic rhinitis
clavulanate, Marbofloxacin,
Amoxicillin Mycoplasma spp., Doxycyclinec 10 mg/kg/24h PO 6 weeksd
marbofloxacin, enrofloxacin
enrofloxacin (Chlamydia felis) Chronic bronchitis/asthma
Pasteurella spp. with Mycoplasma spp.
infection: 6 weeksd
Amoxicillin +
clavulanate, Chronic bronchitis
Clindamycin, with Pasteurella spp.
Pradofloxacin marbofloxacin,
pradofloxacin infection: 2-4 weeks
enrofloxacin,
pradofloxacin
For footnotes, see at the end of the chapter.

* See tables for appropriate diagnostic test

98 99
Feline rhinitis and tracheobronchitis

Second choice antibiotic (with culture and sensitivity testing) Diagnostic approach
If doxycycline cannot be given empirically
Presenting signs Clinical signs
Antibiotics that Syndrome Predispositions Diagnostic tests
Pathogen involved Dosage Duration of treatment may include may include
can be used
Acute rhinitis and Young kittens & Sneezing, nasal & Nasal & ocular Oropharyngeal
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Acute rhinitis & tracheobronchitis tracheobronchitis cats, multicat ocular discharge, discharge, swab for
Marbofloxacin 2 mg/kg/24h PO with Bordetella bronchiseptica with primary household chemosis chemosis, B. bronchiseptica
Bordetella or Mycoplasma spp. bacterial (e.g. shelter, (with Chlamydia blepharospasm PCR &/or culture
bronchiseptica, infection: 7-10 days pathogens e.g. breeding colony), felis), coughing, (with Chlamydia & sensitivity.
Mycoplasma spp. Chronic bronchitis/asthma Bordetella immunocompro- dysphonia, felis especially), Conjunctival swab
Enrofloxacina 5 mg/kg/24h PO with Mycoplasma spp. bronchiseptica, mised, exposure gagging, retching, submandibular for Chlamydia
infection: 6 weeksd Mycoplasma felis to recently ptyalism, lymphadenopathy, PCR,
Acute rhinitis & tracheobronchitis (& Chlamydia felis kennelled dogs. lethargy, tachypnoea, Mycoplasma spp.
10-25 mg/kg/8h 7-10 days; - ocular and nasal inappetence. wheeze/crackles PCR; consider
Amoxicillin
IV, PO Chronic rhinitis disease) on pulmonary FHV & FCV PCRs
Pasteurella spp. 6 weeksd auscultation, (common
20 mg/kg/8h IV Chronic bronchitis increased co-infections).
Amoxicillin +
12.5-25 mg/kg/8-12h with Pasteurella spp. inspiratory effort,
clavulanatee stertor, dehydra-
PO infection: 2-4 weeks
tion, pyrexia.
For footnotes, see at the end of the chapter.
Acute rhinitis and Rhinitis & As above; ocular As above; ocular Evaluation for
tracheobronchitis tracheobronchitis: involvement with involvement with underlying
with secondary primary viral FHV co-infection. FHV, oral ulce- disease e.g. FHV,
bacterial infection infection (FHV, ration with FCV FCV PCRs; aero-
© Angie Hibbert

FCV). co-infection. bic and anaerobic


Rhinitis: bacterial culture
reflux of vomitus & sensitivity,
via nasal cavity, B. bronchiseptica
nasal trauma, and Mycoplasma
neoplasia, fungal spp. PCR on
infection, oronasal nasal flush/biopsy
fistula, dental. &/or bronchoal-
veolar lavage.
Figure 1 - Nasal CT (transverse section)
of a cat diagnosed with acute neutro-
philic rhinitis; Bordetella bronchisepti-
ca was cultured from a nasal flush and
nasal tissue biopsy. The scan image
demonstrates a depressed right nasal
bone fracture and soft tissue/fluid atten- Doxycycline is a suitable empirical treatment choice for upper and
uating material within the nasal meati lower respiratory tract infections however parenteral administration
bilaterally. The fracture was secondary to of an alternative antibiotic is required when bronchopneumonia has
a catfight.
developed or if the cat resents oral pilling due to sinonasal congestion.

100 101
Feline rhinitis and tracheobronchitis

Syndrome Predispositions
Presenting signs
may include
Clinical signs
may include
Diagnostic tests Reasoning
Chronic rhinitis Prior FHV +/- FCV Sneezing Nasal discharge, Evaluation for un- Acute rhinitis and tracheobronchitis primary bacterial pathogens (e.g. from
infection; prior (>1month), nasal loss of air flow via derlying disease a multicat household, recent rehoming
n Infection with feline herpesvirus (FHV)
fungal infection; discharge, nares, increased e.g. FHV & FCV
from a shelter or visit to a cattery).
DISEASE FACT SHEETS

DISEASE FACT SHEETS


idiopathic. +/- epistaxis, inspiratory effort, PCRs, imaging and/or feline calicivirus (FCV) is the
inappetence, stertorous skull (x-ray/ most common cause of acute rhinotra- n Doxycycline is a suitable empirical
lethargy, weight respiration, CT), rhinoscopy, cheitis; development of secondary op- treatment for both primary pathogens
loss. submandibular nasal biopsy (for portunistic infection with commensal and opportunistic bacterial infections
lymphadenopathy. histopathology);
bacteria is a complicating factor. FHV provided the cat can tolerate oral ad-
nasal flush/
biopsy for aerobic and/or FCV co-infection with Bordetel- ministration of medication and there is
and anaerobic la bronchiseptica, Chlamydia felis &/or no evidence of bronchopneumonia. In
bacterial culture Mycoplasma felis (primary pathogens) these circumstances parenteral treat-
& sensitivity, is common in the shelter setting12. In- ment is required.
B. bronchiseptica fection with Streptococcus canis and
and Mycoplasma n Infectious rhinitis and tracheobron-

spp. PCRs. Streptococcus equi subsp zooepidemi- chitis (“cat flu”) is typically diagnosed
cus causing acute URT disease is an based on history and clinical signs
Chronic Asthma-Siamese Cough Tachypnoea, Evaluation for emerging problem in multicat settings2.
bronchitis/asthma and Oriental (paroxysmal with dyspnoea, underlying however evaluation for viral agents,
with complicating breeds. terminal retch), increased disease e.g. n Antibiotics may not be indicated in all Bordetella bronchiseptica, Chlamydo-
bacterial infection acute episodes expiratory effort, imaging cases; supportive treatment (as above) phila felis and Mycoplasma felis infec-
dyspnoea, wheeze/crackles thorax (x-ray/CT); may be adequate in mild cases in adult tion should be considered, especially in
exercise on pulmonary bronchoalveolar cats. Antibiotics should be reserved for cats from multicat settings to guide du-
intolerance, auscultation, lavage
lethargy, hypersensitivity (scope/blind) for
when there is a high clinical suspicion of ration of antibiotic therapy and house-
weight loss. over larynx/ cytology, aerobic bacterial involvement e.g. when ocular hold management e.g. Chlamydophila
trachea. and anaerobic and nasal secretions become purulent felis is treated for at least four weeks
bacterial culture and/or when there is a higher potential and in-contacts should be medicated
& sensitivity, for the cat to have been infected with where there is an endemic infection4,5.
B. bronchiseptica
and Mycoplasma
spp. PCRs;
haematology
and serum
biochemistry,

© Angie Hibbert
faecal analysis for
lungworm.

a b
Figure 2 - a) and b): Thoracic CT scans of a cat diagnosed with severely eosinophilic inflammatory
airway disease with secondary Mycoplasma felis and Bordetella bronchiseptica infection. The images
demonstrate areas of consolidation particularly in the left cranial lung lobe (caudal portion) and a patchy
interstitial (granular-like) pattern in the left caudal lung lobe.

2
102 103
Feline rhinitis and tracheobronchitis

n Identification of FHV may enable use n At the time of investigation, a deep n Chlamydia felis performing a nasal flush for culture and
of anti-viral therapy (e.g. famcyclovir). nasal flush +/- tissue biopsy should be Associated with primary ocular signs sensitivity testing, before switching to
obtained for culture and sensitivity test- and only mild respiratory signs4. another antibiotic; development of
Chronic rhinitis
ing, to guide antibiotic choices since an Pseudomonas spp. resistance may oc-
n Mycoplasma spp.
n The initiating factor is typically prior initial prolonged course of treatment is cur following treatment with commonly
DISEASE FACT SHEETS

DISEASE FACT SHEETS


infection with FHV and/or FCV with sub- recommended (e.g. 6 weeks); growth of Lack a peptidoglycan cell wall there- used antibiotics due to elimination of
sequent secondary bacterial infection in a single bacterial species is more like- fore ß-lactam antibiotics are ineffective; other commensals14. Additionally nasal
65-90% cases14. Opportunistic infection ly to indicate a pathogen7. Nasal swabs duration of treatment is controversial; flushing can be therapeutic.
with commensal bacteria is associat- are not recommended, due to the likeli- sensitivity testing is not routinely avail-
n Pulse antibiotic therapy has previ-
ed with altered mucosal and turbinate hood of sampling the commensal flora; able for Mycoplasma spp.
ously been recommended, however it is
structure and local immune defences. it should be noted that published prev- Chronic rhinitis more likely to lead to the development of
n Potential pathogens include Pseu- alence rates include data based upon antimicrobial resistant commensal bac-
n Multimodal treatment is required to
domonas aeruginosa, Escherichia coli, nasal swab samples. teria and is not advocated.
manage the condition and it is rarely
Streptococcus viridans, Staphylococcus Chronic bronchitis/asthma with com- cured; there will be an on-going re- Chronic bronchitis/asthma with com-
pseudointermedius, Pasteurella mul- plicating bacterial infection quirement for medications (intermittent plicating bacterial infection
tocida, Corynebacterium spp., Actino- n Altered airway structure and function prolonged antibiotic courses, anti-in- n Airway lavage and sampling for cy-
myces spp., Bordetella bronchiseptica, in inflammatory bronchial disease may flammatories, anti-virals if active FHV tology, culture & sensitivity and PCRs
Mycoplasma spp., and all anaerobes6; predispose to opportunistic bacterial in- co-infection) and therapies that help should be performed 5-7 days after the
similar agents may be involved in acute fection and cause acute exacerbations manage nasal secretions (e.g. nebulisa- antibiotic course has been completed (if
cases. of clinical signs. tion, steam therapy, intermittent nasal signs have improved) to guide further
n Empirical antibiotic choices should n The role of Mycoplasma spp. infection
flushing under anaesthesia). treatment (usually corticosteroids +/-
cover a broad spectrum (aerobic and in chronic bronchitis/asthma is not ful- n Considering the recurrent nature of bronchodilators). If severe signs persist,
anaerobic bacteria) with good penetra- ly understood14; Mycoplasma spp. may the disease, repeat culture and sensitiv- anti-inflammatory steroids are com-
tion of bone and cartilage. Doxycycline be part of the normal commensal flora ity is often declined by owners given the menced concurrently with antibiotics. It
is a good first choice, alternatives are of the upper respiratory tract, however requirement for sedation or anaesthesia is important to remember that a clinical
amoxicillin, amoxicillin+clavulanate and identification in the lower airways in the to obtain suitable samples. However, an improvement may not be indicative of
clindamycin. Optimal duration of treat- presence of inflammation is considered inadequate clinical response to an an- successful management of the underly-
ment is unknown. significant and should be treated13. tibiotic chosen empirically or based on ing respiratory disease, due to the cat’s
prior sensitivity testing should prompt ability to mask clinical signs well.
Difficulties and particularities
Acute rhinitis and tracheobronchitis sulfonamides and cephalosporins is a Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
common.
Co-infection with FHV +/- FCV is com- b Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
• Most infections are self-limiting; anti- narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
mon and may be a reason for lack of c Doxycycline hyclate/hydrochloride tablets must be followed with water or food to ensure passage into the stomach
resolution of signs following appropriate biotic treatment is recommended when to prevent development of oesophagitis and/or strictures3.
antibiotic treatment. there are persistent clinical signs >7-10 d Note: initial treatment course for chronic rhinitis is prolonged (e.g. 6 weeks), subsequent flare-ups may be

days, more severe signs or evidence of managed with shorter courses e.g. 2-4 weeks.
n Bordetella bronchiseptica bronchopneumonia and is also recom-
e Use of a ß-lactamase inhibitor (clavulanate) is not usually required for treatment of Pasteurella spp. infections
hence amoxicillin+clavulanate is designated as 3rd choice earlier, however use may be a compromise to achieve
• Resistance to amoxicillin, trimethoprim mended in young kittens (<6-8 weeks)19. patient/owner compliance.

104 105
Bronchopneumonia
and pneumonia
Cats
Bacteria involved Pathogen 1: Pasteurella spp.
Dogs Cats In vitro Tissue Treatment Sensitivity
Results of bacterial Antibiotics that can be used and distribution
sensitivity distribution choice
DISEASE FACT SHEETS

DISEASE FACT SHEETS


cultures and sensitivity 1 = nil
Escherichia coli Pasteurella spp. Amoxicillin 4 3 2 = weak
testing differ
Amoxicillin + clavulanate 4 3 3 = average
significantly in different 4 = good
Bordetella bronchiseptica Bordetella bronchiseptica
studies and Doxycycline 5 4 5 = excellent
geographical regions. Marbofloxacin 5 5 Treatment
Streptococcus spp. Mycoplasma spp. choice
Pradofloxacin b 5 5
1st line
Antibiotics that can be used Pathogen 2: Bordetella bronchiseptica
2nd line
In vitro Tissue Treatment
Dogs Antibiotics that can be used
sensitivity distribution choice Last resort
Pathogen 1: Escherichia coli Amoxicillin + clavulanate 4 3
Excluded
In vitro Tissue Treatment Trimethoprim sulfonamidesc 3 3 for this
Sensitivity
Antibiotics that can be used and distribution indication
sensitivity distribution choice Doxycycline 3 4
1 = nil
Amoxicillin 3 3 2 = weak Marbofloxacin 4 5
Amoxicillin + clavulanate 4 3 3 = average
Pradofloxacin b 4 5
4 = good
Doxycycline 3 4 5 = excellent
a Avoid use in growing dogs of large breeds.
Enrofloxacina 4 5 Treatment
choice b Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
Pradofloxacina,b 4 5 narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
c Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
1st line
testing is recommended if use > 3 weeks7.
Pathogen 2: Bordetella bronchiseptica
2nd line
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice Last resort
Amoxicillin 4 3
Excluded
Amoxicillin + clavulanate 4 3 for this
indication
Trimethoprim sulfonamidesc 3 3
Doxycycline 4 4
Enrofloxacin a 4 5
Pradofloxacina,b 4 5

106 107
Bronchopneumonia and pneumonia

Therapeutic approach Treatment recommendations (mild pneumonia)


Mild pneumonia (stable patient) First choice antibiotic (with C&AST)
Empirical treatment Antibiotics that
Pathogen involved Dosage Duration of treatment
DISEASE FACT SHEETS

DISEASE FACT SHEETS


while awaiting results or if no workup can be used
Escherichia coli Amoxicillin + 12.5-25 mg/kg/8-12h
Doxycycline, clavulanate PO, SC, IV 3-4 weeks,
Bordetella
amoxicillin ± clavulanate until clinical and
bronchiseptica 5 mg/kg/12h
Doxycycline radiographic cure
Pasteurella spp. or 10 mg/kg/24h PO

Marbofloxacin, enrofloxacin
Second choice antibiotic (with C&AST)
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Results of culture and sensitivity Escherichia coli
De-escalate if possible, adapt if necessary Marbofloxacina 2 mg/kg/24h PO, SC, IV
Bordetella
bronchiseptica 3-4 weeks,
Pasteurella spp. Enrofloxacina,d 5 mg/kg/24h PO, SC until clinical and
radiographic cure
Bordetella Trimethoprim
Severe pneumonia (unstable patient) 15-30 mg/kg/12h PO, IV
bronchiseptica sulfonamidesc
Emergency empirical treatment (IV)
while awaiting results a Avoid use in growing dogs of large breeds.
c Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks7.
1st choice broad spectrum combination: d In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.

Amoxicillin, ampicillin, clindamycin IV


+
Marbofloxacin, enrofloxacin IV*

2nd choice broad spectrum combination:


Diagnostic approach
Amoxicillin, ampicillin, clindamycin IV n Bacterial pneumonia seems more radiographs typically display an alveolar
+ common in dogs than in cats. It can be lung pattern (Figure 1) and haematology
Gentamicin IV* caused by primary infectious pathogens, might show leucocytosis with a left shift
aspiration, foreign bodies and by acquired and toxic changes, although these ab-
or congenital immune dysfunction. Pa- normalities are not present in all cases.
Results of culture and sensitivity tients with bacterial pneumonia can In dogs, C-reactive protein can be used
De-escalate if possible, adapt if necessary exhibit clinical signs such as coughing, to differentiate bacterial pneumonia
dyspnoea, tachypnoea, abnormal lung from tracheobronchitis and inflamma-
sounds, lethargy and fever5,8. Thoracic tory respiratory conditions10.
* Marbofloxacin, enrofloxacin and gentamicin are generally considered second-line antibiotics.
However, in emergency situations like these, this is the recommended therapeutic approach.

108 109
Bronchopneumonia and pneumonia

n Bacterial pneumonia can be diag-


nosed by demonstrating suppurative Reasoning
inflammation with intracellular bacteria doxycycline can be a reasonable first-
on bronchoalveolar-lavage-cytology, or if line choice. Doxycycline is especially
bacterial culture reveals significant bac- indicated if B. bronchiseptica or My-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


terial growth (Figure 2, Figure 3). Sam- coplasma spp. infection is suspected,
pling of the upper respiratory tract for although its effectiveness against oth-
culture and sensitivity testing is not help- er bacteria can be very variable9. Many
ful in case of pneumonia, since bacterial respiratory pathogens are susceptible
growth in the upper airways does not to fluoroquinolones, which penetrate
reflect the presence of bacterial path- very well into the respiratory tract; how-
ogens in the lower airways2. The most ever, they are considered second-line
commonly detected bacteria in dogs treatment in animals, because of their

© Bianka Schulz
and cats with lower respiratory tract in- importance in human medicine.

© Bianka Schulz
fections are E. coli, Enterococcus spp.,
n In severely sick animals (severe res-
Streptococcus spp., Staphylococcus spp.,
piratory compromise, signs of sepsis,
B. bronchiseptica, Pasteurella spp., and
see Bacteraemia (sepsis), p.158), a
Mycoplasma spp. However, results of Figure 1 - Radiograph showing bronchoal- combination of IV ampicillin, amoxi-
bacterial cultures and sensitivity testing veolar lung pattern in a dog with bacterial Figure 3 - Cytological picture of broncho-
alveolar lavage fluid of a dog with pneumo- cillin+/-clavulanate, or clindamycin in
can differ significantly in different stud- pneumonia.
nia showing suppurative inflammation with combination with a fluoroquinolone or
ies and geographical regions1,4,5,9. degenerative neutrophils and intracellular aminoglycoside can be indicated for
bacteria. empirical therapy, or while awaiting
C&ST results. De-escalation should be
© Bianka Schulz

n Many bacteria show varying degrees of carried out on the basis of culture and
resistance, especially Enterobacteriaceae sensitivity testing, if available.
and Pseudomonas spp. Therefore, the best n If a patient does not improve three
way to choose the appropriate antibiotic to four days after initiation of empiri-
therapy for an individual patient would cal antibiotic therapy, bronchoalveolar
be to obtain a broncho-alveolar lav- lavage and culture and sensitivity test-
age fluid sample and perform cytology, ing is strongly recommended. In case
culture and sensitivity testing. Howev- of pneumonia following aspiration of
er, in many patients antibiotic therapy foreign material or foreign bodies, good
Figure 2 - Blind bronchoalveolar lavage
procedure in a cat to obtain material for
must be initiated without that infor- anaerobic coverage should be attempt-
cytology, culture and sensitivity testing. mation due to instability of the patient ed. Ampicillin, amoxicillin or clindamy-
Sterile sodium chloride solution (0.9%) is or the owner declining further testing. cin are usually effective against most
applied into the lower airways over a ster- In that case, amoxicillin+clavulanate or anaerobic organisms.
ile catheter inserted into a sterile endotra-
cheal tube and recovered via collection
tube and mechanical suction.

110 111
Bronchopneumonia and pneumonia

Difficulties and particularities


n Treatment failure can be linked to antibiotic treatment for at least 3-4
several factors. If an underlying problem weeks, beyond the resolution of clini-
can be identified (e.g. recurrent aspira- cal signs, laboratory and radiographic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


tion, bronchial foreign body) this needs abnormalities. However, this recom-
to be managed as well to prevent recur- mended time has never been evaluated
rence. in studies in dogs and cats, therefore
n Some pathogens might require specific the optimal duration of treatment is un-
antibiotics, such as Mycoplasma spp., that known and a shorter period of antibiotic
are resistant to ß-lactams. Furthermore, treatment might be indicated based on
mycoplasmas require special culture resolution of all these abnormalities.
media and might therefore be missed n Especially in cats, clinical signs of
with conventional culture methods. pneumonia such as fever, radiographic
n Not all antibiotics penetrate equally changes and left shift can be absent
well into the bronchial tree, which can or subtle and patients presenting with
also be a reason for treatment failure. cough can be falsely diagnosed with in-
Fluoroquinolones, trimethoprim-sulfo- flammatory bronchial disease4,6. There-
namide combinations and doxycycline fore, cats with respiratory signs that do
can reach higher concentrations in the not respond to anti-inflammatory thera-
bronchi than most ß-lactam antibiotics3. py should be evaluated for bacterial path-
n For animals with pneumonia, it has ogens by cytology, culture and sensitivity
traditionally been recommended to give testing of bronchoalveolar lavage fluid.

Thoracic radiographs are essential


for diagnosis, especially in feline
patients.

112 113
Pyothorax in dogs
Pathogen 3: Obligate anaerobes (Peptostreptococcus, Bacteroides...)
Bacteria involved Sensitivity
In vitro Tissue Treatment
Antibiotics that can be used and distribution
sensitivity distribution choice
Bacteria Prevalence Reported associations 1 = nil
Amoxicillin + clavulanate 4 3 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Gram-negative aerobes and 3 = average
Metronidazole 4 3
anaerobes 24%1 to 31% of cases8, 4 = good
Pasteurella spp. 5 = excellent
++ (15 to 40 %) Peptostreptococcus spp. being the Clindamycin 4 5
Escherichia coli Treatment
most frequent anaerobe (27%)
Pradofloxacina,d 4 5 choice
before Bacterioides (25%)
Staphylococcus a Avoiduse in growing dogs of large breeds. 1st line
++ (15 to 40 %) Peptostreptococcus
Corynebacterium b Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It
should only be used if sensitivity testing indicates that other antibiotics would be 2nd line
Nocardia ++ (15 to 40 %) Clostridium ineffective or if oral administration of medication is not possible.
c Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with
Last resort
renal dysfunction (see www.iris-kidney.com/education/prevention.html)
Antibiotics that can be used d Pradofloxacin is a last resort choice due to its very extended spectrum of activity and
should only be used if a narrower spectrum antibiotic cannot be used (based on sensitivity Excluded
for this
If the use of antibiotics is justified: testing results).
indication
Pathogen 1: Gram-positive bacteria (Staphylococcus, Corynebacterium,
Nocardia)
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Amoxicillin or ampicillin 3 3

© Hervé Brissot
2 = weak
3 = average
Amoxicillin + clavulanate 4 3
4 = good
Clindamycin 3 5 5 = excellent
Treatment
Cefalexin / Cefadroxil 4 3 choice
a
Marbofloxacin / Enrofloxacin a 4 5
1st line
Pathogen 2: Gram-negative bacteria (Pasteurella, E. coli...)
2nd line
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice Last resort

Amoxicillin or ampicillin 3 3
Excluded
Amoxicillin + clavulanate 4 3 for this
indication
Marbofloxacina / Enrofloxacina 4 5 Figure 1 - Conservative treatment of
pyothorax. This dog (in sternal recum-
Cefalexin / Cefadroxil 3 3 bency), has 2 chest drains placed, the
Cefovecinb 5 3 pleural cavity is lavaged with saline.
Note the appearance of the pleural effu-
Aminoglycosides c 5 3 sion before initiating the lavage.

114 115
Pyothorax in dogs

Therapeutic approach Treatment recommendations


n Non-antibiotic treatment: imaging, chest drainage with large-bore drains and pleu-
ral lavage, mediastinal surgical debridement.
Emergency empirical treatment (IV) n Sampling for culture and sensitivity testing is highly recommended before start-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


while awaiting results of culture and sensitivity ing antibiotic therapy. It should be done with the initial sample collected for the di-
agnostic thoracocentesis and from tissue collected during exploratory thoracotomy.
Broad spectrum combination therapy: Initial clinical management may indicate the use of IV antibiotics. The use of amino-
glycosides should be carefully evaluated as the general condition of the patient might
Amoxicillin, ampicillin, amoxicillin+clavulanate
+ make these antibiotics unsuitable due to their inherent toxicity.
Clindamycin First choice antibiotic
or Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Alternative combination:
Gram-positive
Clindamycin, metronidazole Amoxicillin
(Gram-negative) 12.5-25 mg/kg/12h
+ and anaerobes
+ clavulanate
Marbofloxacin, enrofloxacin
Staphylococcus, Marbofloxacina 2 mg/kg/24h
or Gram-negative
bacteria Enrofloxacina 5 mg/kg/24h
Alternative combination: 4 weeks minimum
(2 weeks after imaging
Amoxicillin, ampicillin, amoxicillin+clavulanate Obligate anaerobes Metronidazole 15 mg/kg/12h resolution)
+
Marbofloxacin, enrofloxacin ß-haemolytic
Potentiated
(+ metronidazole) Streptococcus,
sulfonamidese
15-30 mg/kg/12h
Pasteurella

Gram-positive and
Clindamycin 5.5-11 mg/kg/12h
obligate anaerobes
a Avoid use in growing dogs of large breeds.
Results of culture and sensitivity e Trimethoprim sulfonamide: avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and
De-escalate if possible, adapt if necessary nephrotoxicity. Schirmer tear testing is recommended if use > 3 weeks5.
(avoid combinations)
Continue antibiotherapy for 4-6 weeks Diagnostic approach
n Pyothorax is a septic pleural effusion. useful to support the diagnosis.
Common clinical signs associated with n Pyothorax may be secondary to lung
pyothorax are lethargy, dyspnoea and infection, perforation/damage to the tho-
hyperthermia. The diagnosis is based racic wall, migration of foreign material,
on the findings of a purulent pleural ef- perforation/damage to the oesophagus,
fusion after thoracocentesis. Imaging or could be a postoperative complication
(radiographs, CT, ultrasonography) is of thoracic surgery. In dogs, it is often

116 117
Pyothorax in dogs

suspected that pyothorax is secondary diverse. Therefore, broad-spectrum an- fluoroquinolones+aminopenicillins.


to the migration/inhalation of a grass tibiotics are recommended until results Several retrospective studies in the UK
awn although physical evidence of in- of the culture and sensitivity tests are and the US showed that treatment was
trapleural vegetal material is rare. known (note that, in up to 40% of the successful in associating amoxicillin +
n There are three stages: exudative (stage I), cases, samples may yield no growth). clavulanate with enrofloxacin and met-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


transitional to fibrinopurulent (stage II), n In pyothorax, mixed populations of ronidazole. See recommendation R.12.
organising or consolidative phase (stage III). aerobes and anaerobes are commonly n Although often efficient in vitro ,

n Traditionally, pyothorax in dogs was found (Pasteurella spp., Nocardia spp. and aminoglycosides are not suitable for
treated conservatively using chest E. coli were the most frequently observed the treatment of pyothorax due to their

© Hervé Brissot
drainage and antibiotics. Clinical expe- aerobes when multiple strict anaerobes potential toxicity in septic patients.
rience shows that dogs are frequent- were cultured). Monotherapy is there- n Treatment is usually conducted for a
ly presented with advance stage II or fore rarely considered sufficient to treat minimum of 4 weeks; cessation of anti-
stage III, making conservative treatment pyothorax. Recommended combination biotic treatment 2 weeks after full reso-
Figure 2 - Thoracoscopic observation of a therapies include: aminopenicillins+clin-
unsuccessful as thorough evacuation pyothorax. Note the severity of the mediasti- lution as confirmed by imaging.
of the pleural cavity is difficult due to nal inflammation and the fibrinous deposits. damycin, fluoroquinolones+clindamycin,
fibrinous obstruction of the drains.
Therefore, surgical debridement needs
to be considered in dogs. For some au- or only after conservative management
thors, surgery carries the best chance of has failed.
recovery. However, there is still no con- n In dogs, the therapeutic approach of
sensus on whether surgery should be this disease differs markedly from that
performed as a first-intention treatment in cats (see Pyothorax in cats, p.122).

Reasoning
n Although one study reported good than an antiseptic or antibiotic solution.
results with a single pleural evacu- In general, drainage is discontinued
ation by thoracocentesis followed by once daily effusion drops below 2 to 5
long-term antibiotics3, the usual rec- ml/kg/24 hours.
ommendation is to establish pleural
n Treatment of the underlying cause,
drainage with a large-bore chest tube,
if necessary by surgery (lung abscess,

© Hervé Brissot
usually bilaterally, in association with
oesophageal damage) is an essential
surgical debridement if needed. Fluid
part of the treatment.
samples should be collected for cy-
tology (Gram stain) and culture and n Parenteral antibiotics (via the intrave- 3 4
sensitivity testing. Pleural lavage is nous route) are recommended until the
Figures 3 - 4 - This dog underwent open surgical debridement of a pyothorax. A sternotomy was
also recommended. Although there is dog is stable, rehydrated and eating vol- necessary to access both sides of the chest. Two large drains have been placed. Note the appearance
no definitive protocol for this, there is untarily. and the size of the inflamed/infected mediastinum.
consensus to use plain saline rather n Bacteria involved in pyothorax are highly

118 119
Pyothorax in dogs

Difficulties and particularities


n Pyothorax is usually diagnosed as an for several days until efficacy is confirmed.
acute infection with systemically affected This is followed by oral medication for 4
patients requiring long-term treatment. to 6 weeks.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Usually, treatment is started by the IV route

Perform thoracocentesis (cytology)


Take sample for C&AST
if bacterial infection

Antibiotherapy:
1. Empirical while awaiting results
2. Adjust based on C&AST results

Chest drainage
Thoracic imaging after drainage

Clinical improvement ?
No Yes

No
Evidence of surgical disease ?
Yes or maybe

Surgical exploration of the chest: Continue drainage/lavage


pleural cavity debridement with appropriate general
and removal of the surgical lesion. antibiotherapy until resolution of
Then continue drainage/lavage the effusion (less than 5ml/kg/24h),
with appropriate then continue antibiotherapy for
general antibiotherapy 4 to 6 weeks and chest radiography
until resolution 2 weeks later
of the effusion. to maintain absence of re-effusion.

Figure 5 - Clinical approach to pleural effusion.

2
120 121
Pyothorax in cats
• Pyothorax is frequently due to a polymicrobial infection of obligate anaerobes +/- Pathogen 2: Obligate anaerobes
facultative anaerobes. (e.g. Bacteroides spp., Fusobacterium spp., Clostridium spp.)
In vitro Tissue Treatment Sensitivity
Bacteria involved 3, 5, 7, 10, 14, 15 Antibiotics that can be used
sensitivity distribution choice and distribution
1 = nil
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Ampicillin / Amoxicillin 4 4 2 = weak
Bacteria Prevalence Reported associations Clindamycin 4 4 3 = average
4 = good
Metronidazole 5 4 5 = excellent
Pasteurella spp. 12-63%
Treatment
Polymicrobial infections with Amoxicillin + clavulanate 5 4 choice
Bacteroides spp. 13-42% obligate and facultative anaerobes Cefovecin b 3 4
are very common. 1st line
Pradofloxacinc 5 4
Fusobacterium spp. 13-23%
b Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It 2nd line
should only be used if sensitivity testing indicates that other antibiotics would be ineffective
or if oral administration of medication is not possible. Last resort
c Pradofloxacin is a last resort choice due to its very extended spectrum of activity and

Antibiotics that can be used 6, 11, 12, 15 should only be used if a narrower spectrum antibiotic cannot be used (based on sensitivity
testing results).
Excluded
for this
indication
Empirical choice: amoxicillin+clavulanate or ampicillin/amoxicillin/clindamycin +
fluoroquinolone (marbofloxacin preferred) pending culture and sensitivity results.
Pathogen 1: Pasteurella spp.
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Ampicillin / Amoxicillin 4 4 2 = weak
3 = average
Amoxicillin + clavulanate 5 4
4 = good
Marbofloxacin 5 5 5 = excellent
Treatment
Enrofloxacina 5 5 choice
Cefovecin b 4 4
1st line
Pradofloxacinc 5 4
2nd line
a Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not
exceed 5 mg/kg.
b Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It Last resort
should only be used if sensitivity testing indicates that other antibiotics would be ineffective
or if oral administration of medication is not possible. Excluded
c Pradofloxacin is a last resort choice due to its very extended spectrum of activity and for this
should only be used if a narrower spectrum antibiotic cannot be used (based on sensitivity indication
testing results).
The primary cause of feline pyothorax is considered to be a parapneumonic infection secondary
to inhalation of oropharyngeal bacteria and pneumonia e.g. following upper respiratory infection
with FCV or FHV.

122 123
Pyothorax in cats

Therapeutic approach Treatment recommendations


n Adjunctive (non-antibiotic) treatment: oxygen therapy (if dyspnoeic), intravenous
Pleural fluid analysis suggestive of pyothorax fluid therapy to address shock +/- dehydration, electrolyte and acid-base derange-
Empirical treatment while awaiting results ments if present, thoracocentesis to remove pleural exudate, placement of thoracos-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


of culture and sensitivity
tomy tubes for intermittent pleural drainage and lavage with sterile isotonic fluids,
nutritional support (if inappetent), analgesia.
Amoxicillin ± clavulanate n Empirical choice pending culture and sensitivity: amoxicillin+clavulanate or a
combination of ampicillin/amoxicillin/clindamycin + fluoroquinolone (marbofloxacin
or preferred).
Ampicillin, amoxicillin, clindamycin These choices will be effective against obligate and facultative anaerobic organisms
+ (including Pasteurella spp.) and should be administered parenterally (preferably in-
Marbofloxacin, enrofloxacin* travenously if appropriate formulation available).
n The antibiotic(s) will then need to be modified:

• according to culture and sensitivity results (include anaerobic cover; false negative
anaerobic cultures possible).
Results of culture and sensitivity
De-escalate if possible, adapt if necessary • by formulation, moving to oral preparations once the cat is stable, hydrated
(avoid combinations) and eating.
Continue antibiotherapy for 4-6 weeks n Duration of treatment is typically extended (e.g. 4-6 weeks) and guided by repeat tho-
racic imaging to check for resolution of effusion. Current recommendations are for anti-
biotics to be continued for at least one week following resolution of thoracic effusion.
Obligate anaerobes
Pasteurella spp. (false negatives possible) First choice antibiotic (empirical choice or after culture and sensitivity testing)
Antibiotics that
Amoxicillin, ampicillin, Amoxicillin, ampicillin, Pathogen involved Dosage Duration of treatment
can be used
amoxicillin+clavulanate clindamycin
10-20 mg/kg/8h IV;
Ampicillin (sodium) not recommended for
Amoxicillin + clavulanate, oral treatment
Marbofloxacin, enrofloxacin Pasteurella spp.
metronidazole Amoxicillin 10-25 mg/kg/8h IV, PO

Amoxicillin + 20 mg/kg/8h IV
clavulanate 12.5-25 mg/kg/8-12h PO
Pradofloxacin, cefovecin Pradofloxacin, cefovecin 4-6 weeks
10-20 mg/kg/8h IV;
Ampicillin (sodium) not recommended for
oral treatment
* Ampicillin, amoxicillin and clindamycin are generally considered first-line antibiotics. Obligate anaerobes
However, this broad-spectrum combination includes fluoroquinolones, and is therefore Amoxicillin 10-25 mg/kg/8h IV, PO
less preferred.
Clindamycin 5.5-11 mg/kg/12h IV, PO

124 125
Pyothorax in cats

Second choice antibiotic (following culture and sensitivity testing) Reasoning


Antibiotics that
Pathogen involved Dosage Duration of treatment n Successful management of pyothorax n Culture and sensitivity testing should
can be used
requires systemic antibiotic treatment be performed upon samples of pleu-
Marbofloxacin 2 mg/kg/24h IV, SC, PO and thoracic drainage (typically with ral effusions obtained before antibiotic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Pasteurella spp. indwelling thoracostomy tubes; small treatment is administered and the an-
Enrofloxacina 5 mg/kg/24h SC, PO bore 14G tubes are well tolerated by tibiotic should be modified according to
4-6 weeks cats) +/- lavage with isotonic fluids. culture results.
Amoxicillin 20 mg/kg/8h IV
+ clavulanate 12.5-25 mg/kg/8-12h PO n Nocardia spp. infections may occur
n Parenteral antibiotics (via the intrave-
Obligate anaerobes but may not be recovered on bacterial
nous route) are recommended until the
Metronidazole 10-15 mg/kg/12h IV, PO
cat is stable, rehydrated and eating vol- culture. Grossly there may be sulphur
a In untarily. granules in the effusion and cytological-
cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
ly Nocardia spp. appear as Gram-pos-
n Empirical treatment can be chosen itive acid-fast bacteria. Treatment of
on the basis of cytological examination choice is trimethoprim sulfonamide.
of the effusion, pending culture results;
Diagnostic approach Gram-negative bacilli most often are
n Adjunctive care is very important in
addressing fluid, acid-base and electro-
n Presenting signs may include dysp- • Pleural fluid bacterial culture - aerobic Pasteurella spp., infection with Entero- lyte derangements, providing nutritional
noea, tachypnoea, cough, inappetence, and anaerobic; pay particular attention to bacteraciae spp. are infrequent com- support (e.g. feeding via a naso-oesoph-
lethargy, dehydration, ptyalism and maximising potential for identification of pared to canine pyothorax. ageal tube) and analgesia (e.g. opioid
weight loss14. anaerobes (see Recommendation R.4) n The antibiotic should be effective analgesia buprenorphine 0.01-0.02mg/
n Abnormalities on physical examina- and consider PCR for Mycoplasma spp. kg IV q6-8hrs) whilst thoracostomy
against anaerobic bacteria since the
tion may include signs of shock (pallor, majority of infections are due to ob- tubes are in situ.
tachycardia or bradycardia, poor pe- ligate and/or facultative anaerobes; n Surgical treatment is indicated in the
ripheral pulses, hypothermia) and de- amoxicillin+clavulanate or a combina- following scenarios: identification of a
hydration, muffled heart sounds, loss of tion of ampicillin/amoxicillin/clindamy- foreign body, pulmonary or mediastinal
pulmonary sounds in the ventral thorax, cin with a fluoroquinolone (marbofloxa- abscess, failure of medical therapy (e.g.
pyrexia and reduced body condition2,14. cin preferably) are reasonable empirical lack of cytological improvement, persis-
n The diagnosis is confirmed by: choices initially. tent infection or effusion after 5-7days).
© Angie Hibbert

• Identification of pleural effusion – us-


ing thoracic ultrasound, radiography/ Difficulties and particularities
computed tomography (if patient is sta- n The primary cause of feline pyothorax haematogenous spread, oesophageal
ble enough) or blind thoracocentesis. is considered to be a parapneumonic perforation and bacterial infection sec-
Figure 1 - Cytology of thoracic effusion in
• Pleural fluid analysis (cytology and a cat diagnosed with pyothorax. The im- infection secondary to inhalation of oro- ondary to parasitic visceral migration3.
biochemical) - septic exudate (predom- age shows degenerate neutrophils and a pharyngeal bacteria and pneumonia e.g. n A search for an underlying cause that
branching fusiform bacillus confirmed as following upper respiratory infection
inantly neutrophils (degenerate) +/- in- Actinomyces spp. on bacterial culture (mod- may need specific treatment should be
tracellular and extracellular bacteria) ified Wright’s stain, x 1000). with FCV or FHV. Other causes include made, by repeating thoracic imaging
with high protein levels (>30g/l). bite wounds, migrating foreign bodies, following complete evacuation of the

126 127
Pyothorax in cats

pleural exudate. may occur due to pocketing or inspissa-


tion (thickening) of exudate, pulmonary
n Pyothorax may be unilateral or bilateral
or mediastinal abscess, inadequate
depending upon whether the mediasti-
length of antibiotic treatment or lack of
num is intact.
culture to guide appropriate antibiotic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


n Following placement of a single thora- choice.
costomy tube, imaging should be re- n The prognosis for pyothorax is gener-
peated to ensure that effective drainage ally good, however patients with indwell-
has been achieved and if not, bilateral ing thoracostomy tubes and those re-
thoracostomy tubes should be placed. quiring surgical treatment typically need
Failure of medical treatment thereafter intensive care treatment and monitoring.

Adjunctive care is very important in addressing fluid, acid-base and electrolyte derangements,
providing nutritional support (e.g. feeding via an naso-oesophageal tube) and analgesia (e.g. opi-
oid analgesia buprenorphine 0.01- 0.02mg/kg IV q6-8hrs).

2
128 129
DISEASE FACT SHEETS

130
Dermatology

131

DISEASE FACT SHEETS


Surface AND
superficial pyoderma
• In surface pyoderma (e.g. skin fold pyoderma, “hot spots” and bacterial over-
growth), topical disinfectant treatment suffices. No systemic antibiotics should be
Therapeutic approach
used.
• In superficial pyoderma (e.g. impetigo, bacterial folliculitis, mucocutaneous pyoder- Localised lesions Widespread lesions
ma), topical disinfectants usually suffice. If this fails and systemic antibiotic treat-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


ment is required, see Deep pyoderma p.138. Cytology for diagnosis
Surface pyoderma: Bacterial overgrowth ± Malassezia without neutrophils
Bacteria involved Superficial pyoderma: Presence of neutrophils with intracellular bacteria

Bacteria Prevalence Reported associations Daily disinfectant gel, Shampoo twice weekly +
spray, creams daily disinfectant spray,
Bacterial overgrowth can be associated mousse, wipes mousse, wipes
Staphylococcus spp. +++++ (> 75 %)
with Malassezia pachydermatitis

Escherichia coli + (< 10-20 %) When present, E. coli and Pseudomonas


are often in association Treat topically until clinically cured and cytology is negative (usually ≥ 2-3 weeks)
Pseudomonas aeruginosa + (< 10-20 %) with Staphylococcus spp.

Antiseptics that can be used In case of treatment failure,


In case of treatment failure,
consider fucidic acid or
Antibiotics should preferably not be used in cases of surface and superficial systemic antibiotics
consider systemic antibiotics
pyoderma. Antiseptics should be used instead. (see Deep pyoderma)
(see Deep pyoderma)

In vitro Tissue Treatment Sensitivity and


Antiseptic that can be used distribution
sensitivity distribution choice
1 = nil
Chlorhexidine 2-4% shampoo 5 topical 2 = weak
3 = average
Chlorh.* wipes, mousse, spray 5 topical
4 = good
Benzoyl peroxide 2.5% 3 topical 5 = excellent

Ethyl lactate 10% 3 topical Limited clinical evidence Treatment


choice

© Chiara Noli
Triclosan 5 topical No clinical evidence
1st line

© Chiara Noli
Hypochlorous acid 5 topical No residual efficacy, use daily
Bleach 4% 5 topical Daily soak 2nd line

Benzalconium chloride 4 topical No clinical evidence Last resort


Cytological aspect of the content of a pustule in
a case of superficial pyoderma: several neutro-
Medical honey 5 topical Do not mix with other topicals Cytological appearance of surface pyoderma:
phils, including degenerate neutrophils, are
Excluded numerous bacteria are observed with the pre-
Fusidic acid 5 topical For localized lesions only visible, some of which contain coccal bacterial
for this sence of mature corneocytes but with the ab-
indication elements in the cytoplasm (arrows) (Diff Quik®,
Mupirocin 5 topical Not licensed for animal use sence of inflammatory cells.
1000x).
* Chlorhexidine

132 133
Surface and superficial pyoderma

Treatment recommendations How to sample for cytological examination


n Topical or systemic antibiotics should In case of suspect bacterial overgrowth, cytological samples can
not be used as a first-line treatment in be collected directly from plain skin by impression of a glass
cases of bacterial overgrowth, intertrigo slide or (better) of a clear adhesive tape. Material can also be collected
DISEASE FACT SHEETS

DISEASE FACT SHEETS


(skin fold pyoderma) and hot spots by superficial scraping smeared on a glass slide.
(pyotraumatic pyoderma) or in cases Skin folds can be sampled with a dry or moist cotton swab, which is then rolled
of uncomplicated superficial pyoderma (not smeared!) on the glass slide.
(superficial folliculitis, impetigo, mucocu- Cytology from open exudative lesions, collarettes or from under a crust is per-
taneous pyoderma). Antiseptic products formed with an impression smear. Pyotraumatic dermatitis is sampled by an im-
should be used instead. pression smear on the moist surface. Pustules are carefully opened with a small
n For widespread lesions, an antiseptic needle and their content is gently pressed on a glass slide without smearing, in
shampoo with a 10-minute contact time order to avoid artefacts (nuclear stripes).
should be used at least twice weekly. Glass slides and clear adhesive tape can be stained with rapid haematology kits

© Chiara Noli
A disinfectant spray, mousse or wipe and examined in the practice.
should be applied daily on the lesions
on the days that the animal is not sham-
pooed. Hot spot (pyotraumatic dermatitis) on the back Reasoning
n In more localised lesions, antimicrobial of a dog with flea bite allergy.
n In all cases of surface and superficial n Topical antibiotics should only be
sprays, gels, lotions, creams, mousses
pyoderma, whether localised or gener- used in localized, deep lesions, where
or wipes can be used daily. systemic ones. Please refer to Deep alised, topical treatment with disinfect- disinfectants would fail to penetrate.
n Topical therapies should be applied pyoderma, p.138, for the systemic anti- ants is preferred, in order to decrease
until clinically and cytologically cured biotic choice. antibiotic use and the development of
(usually 2-3 weeks). n The identification and control of an bacterial resistance. Chlorhexidine has
n Topical or systemic antibiotics should underlying disease (allergy, endocrine, demonstrated excellent in vitro and in
be used only if topical antiseptic ther- anatomic defect, etc.) is mandatory for vivo efficacy and has residual activity
apy is not successful or not possible. therapeutic success and in the preven- on the skin. Furthermore, it is effective
Topical antibiotics are to be preferred to tion of relapse. on both sensitive and multidrug-re-
sistant staphylococci, with no need for
Diagnostic approach bacterial culture and sensitivity testing
prior to starting treatment. Resistance
n Like any other dermatological condi- nation of the skin surface or exudate

© Chiara Noli
to chlorhexidine is very rare in staphy-
tion, the approach to surface and super- will confirm the diagnosis by showing lococci, although it has been described
ficial pyoderma should include a detailed the presence of bacteria without neutro- in Pseudomonas. Other topical disin-
history and a general examination. As phils (in surface pyoderma) or bacteria fectants are either more irritant, less
most pyoderma is a complication of an within (phagocytosed by) neutrophils (in effective or have insufficient published Skin fold pyoderma on the muzzle of a pug.
underlying disease, this should be iden- superficial pyoderma, such as impetigo, evidence of their efficacy.
tified and controlled in order to obtain a bacterial folliculitis and mucocutaneous
long-lasting cure. A cytological exami- pyoderma).

134 135
Surface and superficial pyoderma

Difficulties and particularities


n Shampoos should be applied at the
right concentration, massaged in the
hair and on the skin and left in place
DISEASE FACT SHEETS

DISEASE FACT SHEETS


for 10 minutes. Animals should then be
rinsed well. A cleansing shampoo can
be used before the disinfectant product.
Failure to use the right concentrations
or to leave in place long enough can lead

© Marie-Christine Cadiergues
to insufficient efficacy.
n In case of treatment of localised le-
sions with creams or gels it is important
to prevent the animal from licking them.
An Elizabethan collar or distraction (e.g.
playing, walking, feeding) for 10-15 min-

© Catherine Laffort
utes can be of help.
n Bacterial biofilm formation is a fre-
Folliculitis of bacterial and parasitic origin
quent cause of treatment failure, as (demodicosis).
it prevents antibiotics and antiseptics
Collarette, a typical lesion of superficial pyoderma.
from reaching the causative agents.
Also, antibiotics that act during bacte-
rial replication will not be effective be-
cause in biofilms microorganisms are
usually quiescent and do not multiply.
Specific cleaning agents with biofilm
disrupting properties, such as Tris-EDTA
or detergent scrubs should be used in
these cases.
n Underlying disease: superficial and
© Chiara Noli

surface pyoderma are generally compli-


cations of an underlying disease. If this
is not identified and controlled, the skin
infection will not cure or will relapse.
Bacterial overgrowth with hyperpigmentation, Common underlying diseases are at-
lichenification and a moist greasy exudate on
the abdomen of an allergic German Shepherd
opic dermatitis, food or fleabite allergy,
dog. parasites (Demodex), endocrine disease
and keratinization disorders.

2
136 137
Deep pyoderma
• This chapter deals with the diagnosis and treatment of deep pyoderma (furunculosis, Pathogen 2: Meticillin (multidrug) resistant Staphylococcus spp.
ulceration, draining tracts with a haemopurulent exudate...).
Antibiotics to be used only if sensitivity tests show resistance to the antibiotics
• For superficial pyoderma (e.g. impetigo, bacterial folliculitis, mucocutaneous pyoder- mentioned for meticillin-sensitive antibiotics.
ma), topical treatment usually suffices (see previous chapter). However, in case systemic
In vitro Tissue Treatment Sensitivity
antibiotic treatment is required, the recommendations in this chapter can be followed.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Trimethoprim sulfonamidesb 3 4 2 = weak
Bacteria involved Doxycycline / Minocycline 4 5 3 = average
4 = good
Marbofloxacinc / Enrofloxacinc,d 4 4 5 = excellent
Bacteria Prevalence Treatment
Pradofloxacin c,e 4 4 choice
Meticillin sensitive Rifampicinf 3 5
++++ (>60%) 1st line
Staphylococcus spp.
Chloramphenicol / Florfenicol 3 4
Meticillin resistant, multidrug-resistant
+ (<10-20%) Gentamicing 5 4 2nd line
Staphylococcus spp.
Amikacing 5 4 Last resort
Pseudomonas + (< 10-20 %)
Pathogen 3: Pseudomonas aeruginosa Excluded
Escherichia coli + (< 10-20 %) for this
In vitro Tissue Treatment indication
Antibiotics that can be used
sensitivity distribution choice

Antibiotics that can be used Marbofloxacinc / Enrofloxacinc,d 4 4


Gentamicin g 5 4
Systemic antibiotics that can be used (for topical therapy, see Surface and Amikacin g 5 4
superficial pyoderma, p.132). Ticarcillin + clavulanate 4 4
Sensitivity
Pathogen 1: Meticillin sensitive Staphylococcus spp. and distribution
Imipenem 5 5
1 = nil
In vitro Tissue Treatment 2 = weak
Pathogen 4: Escherichia coli
Antibiotics that can be used
sensitivity distribution choice 3 = average In vitro Tissue Treatment
4 = good Antibiotics that can be used
Amoxicillin +/- clavulanate 5 4 sensitivity distribution choice
5 = excellent
Cefalexin / Cefadroxil 5 5 Treatment Amoxicillin + clavulanate 3 4
choice
Clindamycin 3 4 Cefalexin / Cefadroxil 3 5
Cefovecin a 5 5 1 line
st
Trimethoprim sulfonamides b 4 3
For footnotes, see at the end of the chapter. Cefovecina 5 5
2nd line
c
Marbofloxacin / Enrofloxacin c,d 4 5
Last resort
Pradofloxacin c,e 4 5

Excluded Rifampicin f 5 5
for this
indication Aminoglycosides g 5 4
For footnotes, see at the end of the chapter.

138 139
DEEP pyoderma

Therapeutic approach Treatment recommendations


n Topical non-antibiotic treatment should
Therapeutic approach for deep pyoderma and for superficial pyoderma that is
be preferred in cases of superficial pyo-
unresponsive to topical treatment.
derma (see previous chapter). Systemic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


antibiotics should be reserved for cases
Cytology for diagnosis of topical treatment failure or in the
- presence of intracellular bacteria (pyoderma) case of deep pyoderma.
- identification of cocci and/or rods
n The administration of empirical anti-
biotics (without culture and sensitivity
testing) is acceptable only in first-occur-
rence superficial coccal pyoderma.
Empirical treatment Culture & AST in case of: n In all other cases, bacterial culture

© Catherine Laffort
only in case of: - deep pyoderma
- superficial pyoderma with failed - presence of rods and sensitivity testing should be per-
topical treatment - relapsing pyoderma (cocci and rods) formed first .
- first occurence of superficial - failure of empirical treatment n Systemic antibiotics should be ad-
coccal infections - previous antibiotic treatment
ministered for a minimum of 3 weeks in
the case of superficial pyoderma and 4 Pedal cellulitis.
Amoxicillin + clavulanate, Amoxicillin + clavulanate weeks in deep pyoderma.
cefalexin, cefadroxil, clindamycin cefalexin, cefadroxil, clindamycin

Enrofloxacin,
marbofloxacin, cefovecin

Pradofloxacin, rifampicin,
In case of treatment failure,
chloramphenicol, fosfomycin,
perform culture and AST
aminoglycosides

© Chiara Noli
Cytological aspect of a lesion of deep pyo-
Treat until one week beyond clinical cure for superficial pyoderma and two weeks derma: both neutrophils and activated mac-
beyond clinical cure for deep pyoderma (usually at least 3-4 weeks) rophages are visible (pyogranulomatous
inflammation), but no bacteria, in spite of
positive bacterial culture results (Diff Quik®,
1000x).

140 141
DEEP pyoderma

First choice antibiotic Diagnostic approach


Antibiotics that n Deep pyodermas are characterised
Pathogen involved Dosage Duration of treatment
can be used
clinically by furunculosis, ulceration or
Amoxicillin+clavulanate 12.5-25 mg/kg/12h PO 10-15 mg/kg/24 SC draining tracts with a haemopurulent
DISEASE FACT SHEETS

DISEASE FACT SHEETS


in dogs
Cefalexin 15-30 mg/kg/12h PO 1 week beyond cure for exudate, as seen in cases of pyodemod-
Meticillin sensitive superficial pyoderma, icosis, callus infection and interdigital
Staphylococcus spp. 15-30 mg/kg/12h PO or 2 weeks beyond cure for
Cefadroxil 30-40 mg/kg/24h PO
nodules.
deep pyoderma.
n The approach to all types of pyoderma
Clindamycin 5.5-11 mg/kg/12h PO
starts with a detailed history and a general
examination. As most pyodermas are

© Marie-Christine Cadiergues
Second choice antibiotic (following culture and sensitivity testing): complications of an underlying disease
only if bacteria are resistant to the first-choice antibiotics. (allergy, demodicosis, endocrinopathy,
keratinization disorder) this should be
Antibiotics that
Pathogen involved Dosage Duration of treatment identified and controlled in order to ob-
can be used
tain a lasting cure. In superficial pyo-
Trimethoprim 10-15 mg/kg/24 SC
15-30 mg/kg/12h PO derma, cytological examination of the
sulfonamidesb in dogs
exudate will confirm the diagnosis by
Marbofloxacinc 2 mg/kg/24h PO the presence of microorganisms within
Deep callus infection on an elbow.
Enrofloxacin c,d
5 mg/kg/24h PO neutrophils. In deep pyoderma, cytology
will probably show pyogranulomatous
Doxycycline 10 mg/kg/24 h PO inflammation but bacteria are not al- case, bacterial culture and sensitivity
Minocycline 20 mg/kg/12h PO ways seen. In these cases, bacterial cul- testing is mandatory for the correct an-
ture will confirm the diagnosis. In any tibiotic choice.
Rifampin f
5-10 mg/kg/12h PO 1 week beyond cure for
Meticillin-resistant,
superficial pyoderma,
multidrug-resistant
Staphylococcus spp.
Chloramphenicol 50 mg/kg/8h PO 2 weeks beyond cure for How to sample for cytology and bacterial culture
deep pyoderma.
E. coli Fosfomycin 50 mg/kg/12h PO Cytology from open exudative lesions, from collarettes or from
Ps. aeruginosa 10-15 mg/kg/24h SC under a crust is performed on an impression smear. Pustules
in dogs are carefully opened with a small needle and their content is gently
Gentamicing
5-8 mg/kg/24h SC pressed on a glass slide without smearing in order to avoid artefacts (nuclear
in cats stripes).
15-30 mg/kg/24h SC in Sampling for bacterial culture from superficial lesions is ideally performed by
dogs
Amikacing opening an intact pustule and collecting the pus with a sterile cotton swab. In the
10-15 mg/kg/24h SC
in cats absence of intact pustules, the sterile swab can be rubbed along the edges of a
collarette, from under a crust or from open exudative lesions. Sampling for bacte-
Minimum 2 injections,
Cefovecina
8 mg/kg single dose
suitable only in case of rial culture from deep lesions should best be performed by fine needle aspiration
SC (14d) from the depth of a lesion or by skin biopsy, after surface disinfection. Collecting
compliance problems
exudate expressed from the depth of a lesion by squeezing it is also acceptable.
For footnotes, see at the end of the chapter.

142 143
DEEP pyoderma

Reasoning
n In the case of deep pyoderma or un- failure of empirical antibiotic treatment,
successful topical treatment of superfi- deep pyoderma, recurrent infections or
cial pyoderma, systemic therapy is jus- the presence of rods in cytology, antibi-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


tified. The antibiotic of choice should be otics should always be chosen following
based on bacterial culture and sensitiv- bacterial culture and sensitivity testing
ity testing. The only exception would be and following current guidelines. Sec-
first-occurrence superficial coccal pyo- ond-line antibiotics should be used only
derma, in animals that were not treat- in case of resistance to first-line drugs,
ed with antibiotics before. In this case, while third-line antibiotics should only
empirical therapy with first-generation be used in case of resistance to first and
cephalosporins, amoxicillin+clavulanate second-line antibiotics.
or clindamycin can be tried. In case of

Difficulties and particularities


n Treatment failure in the case of super- corticosteroids (1mg/kg/24h for 5 days)
ficial and deep pyoderma may be due to: or long-term immunomodulatory drugs
- wrong diagnosis (e.g. the pustular (e.g. ciclosporine 5mg/kg/24h).
eruption is not due to impetigo but to
pemphigus foliaceus),
- undetected or untreated underlying
disease (e.g. atopic dermatitis, demod-
icosis),
- insufficient duration of antibiotic treat-
ment (e.g. interrupted as soon an im-
provement is observed),
- incorrect administration (dosage, in- a Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
tervals, on an empty vs. full stomach, not possible.
poor owner compliance), b Avoiduse longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear testing
© Catherine Laffort

- ineffective antibiotic (bacterial resist- is recommended if use > 3 weeks 28.


c Avoid use in growing dogs of large breeds.
ance).
d In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
n In some cases of deep pyoderma, such e Pradofloxacin
is a last resort choice due to its very extended spectrum of activity and should only be used if a
as callus pyoderma or interdigital fu- narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
runcolosis, it can be useful to decrease Furunculosis.
f Hepatotoxic, refer to National regulations regarding use.
the inflammation with a short course of g Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).

2
144 145
Otitis externa and media
Pathogen 2: Pseudomonas aeruginosa
Bacteria involved
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
Bacteria Prevalence Reported associations 1 = nil
Polymixin B 5 topical; 2 = weak
Inactivated in pus
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Staphylococcus spp. ++++ (> 60 %) 3 = average
Bacterial otitis is often polybacterial Silver sulfadiazine 5 topical
4 = good
Gentamicin a 5 topical 5 = excellent
Pseudomonas aeruginosa ++ (15 to 40 %)
Otic bacterial overgrowth can be Treatment
Marbofloxacin / Enrofloxacin 5 topical choice
Proteus mirabilis + (< 10-20 %) associated with Malassezia spp. yeasts
Pradofloxacin 5 topical
1st line
Escherichia coli + (< 10-20 %) Amikacina 5 topical
Ticarcillin 5 topical 2nd line
ß-haemolytic streptococci + (< 10-20 %)
Ceftazidime 5 topical Last resort
Klebsiella spp. + (< 10-20 %) a Do not mix with acidic cleaners.
Excluded for
this
Antibiotics that can be used (topically) indication

Topical antibiotics are only to be used if there is no evidence of a ruptured


tympanic membrane and/or otitis media.
Systemic antibiotics should be used only following bacterial culture and
susceptibility testing in case of a ruptured tympanic membrane and/or otitis media.
In this case refer to antibiotics described in Deep pyoderma, p.138.
Pathogen 1: Staphylococcus spp.
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice

© Marie-Christine Cadiergues
1 = nil
Neomycin 5 topical;
Inactivated in pus 2 = weak
Fusidic acid 5 topical 3 = average
4 = good
Framycetin 5 topical 5 = excellent
Florfenicol 5 topical Treatment
choice
Gentamicin a 5 topical
1st line
Marbofloxacin / Enrofloxacin 5 topical
Pradofloxacin 5 topical 2nd line A cytological examination of the otic exudate will determine the presence and the nature of the
microorganisms (yeasts or bacteria, cocci or rods, mixed infections) and of pus (presence of neutro-
Amikacina 5 topical phils).
Last resort
a Do not mix with acidic cleaners.
Excluded for
this
indication

146 147
Otitis externa and media

Therapeutic approach Treatment recommendations


n Otologic examination and cytological therapy, to be continued for one month
• MANAGEMENT OF OTITIS sampling should be performed in every beyond obtaining a negative cytology.
• Identification and correction of underlying cause otitis case: the former to determine if n Systemic and/or topical corticoster-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


• Evaluation of tympanic membrane and middle ear the tympanic membrane is intact, the oids are needed in case of oedema, tis-
second to determine the micro-organ- sue proliferation and ear canal stenosis,
ism involved in the infection. for a minimum of 2 weeks.
Tympanic membrane intact, Ruptured tympanic membrane n If there is no evidence of a ruptured n The identification and control of the
no evidence of otitis media and/or evidence of otitis media tympanic membrane or otitis media, a predisposing, primary and perpetuating
topical antibiotic will be sufficient, until factors is mandatory for the successful
cytology becomes negative. treatment of otitis.
n The ears should be flushed as nec- n In severe cases with unsuccessful
Cytology Culture and sensitivity essary with a disinfectant solution prior treatment, consider referral to a spe-
to application of topical antimicrobial cialist (who may consider surgery).

Treat TOPICALLY until cytological testing is negative. SYSTEMIC antibiotic


Flush daily with topical disinfectant, at least one hour (see Deep pyoderma, How to sample for cytological and bacterial culture
prior to applying the TOPICAL antibiotic. p.138) for 3-6 weeks
For cytological and culture samples from the vertical canal, a cotton
swab is simply inserted in the ear (no sedation required). For samples
from the horizontal ear canal or from the bulla, the animal has to be anaesthetised
and samples should be taken under video-otoscopic guidance.
Yeasts Rods (bacilli) Cocci
Neomycin,
Polymixin B, fusidic acid,
Antifungals
silver sulfadiazine framycetin, Diagnostic approach
florfenicol
n Like any other dermatological con- or if topicals suffice.
Gentamicin, Gentamicin,
dition, the approach to otitis should in- n A cytological examination of the otic
marbofloxacin, marbofloxacin, clude a detailed history and a general exudate will determine the presence
enrofloxacin enrofloxacin examination. As most otitis is a com- and the nature of the microorganisms
plication of an underlying disease, this (yeasts or bacteria, cocci or rods, mixed
Pradofloxacin, should be identified and controlled in infections) and of pus (presence of neu-
Pradofloxacin,
ticarcillin,
amikacin
amikacin order to obtain a lasting cure. An oto- trophils). In case a systemic antibiotic is
scopic examination (preferably after a needed (ruptured tympanic membrane,
thorough ear flushing) will determine if otitis media), then sampling for bacterial
the tympanic membrane is intact, and culture and sensitivity testing is pivotal
thus if systemic antibiotics will be needed for the choice of the systemic antibiotic.

148 149
Otitis externa and media

n The presence of otitis media, even


Reasoning with an apparently intact tympanic
n If the infection is limited to the exter- membrane, will hinder the cure and pre-
nal ear (otitis externa), i.e. if the tympan- dispose to frequent relapses. A (video)
ic membrane is not ruptured and there otoscopic examination will permit the
DISEASE FACT SHEETS

DISEASE FACT SHEETS


is no evidence of otitis media, topical identification of a ruptured or convex
antibiotic treatment (chosen according tympanic membrane, both indicative of
to the guidelines) is usually sufficient. otitis media. Diagnostic imaging such as
open mouth RX, bullae ultrasound, CT

© Marie-Christine Cadiergues
This is because, after topical applica-
tion, the antibiotic concentration pres- scan or MRI allow identification of dam-
ent in the external ear canal is many age to the bulla and otitis media.
times above the MIC of any bacteria. n Bacterial biofilm formation is a fre-

n In any other case, a systemic antibi- quent cause of treatment failure be-
otic, chosen following sensitivity testing cause it hinders antibiotics and antisep-
and guidelines for deep pyoderma (pre- tics reaching the causative agents. Also,
vious chapter) should be administered antibiotics that act during bacterial rep-
for 3-4 weeks, together with the topical lication will not be effective, because in

© Chiara Noli
Suppurative otitis externa with erosive le-
therapy. biofilms, microorganisms are usually sions of the ear canal following infection with
quiescent and do not multiply. Specific Proteus mirabilis.
n Other important aspects of otitis
cleaning agents with biofilm-disrupting
treatment include daily ear flushing with
The cytological appearance of Pseudomonas properties, such as acetyl cysteine or n Recalcitrant Pseudomonas otitis can
a disinfectant and astringent solution otitis: numerous bacterial rods are visible tris-EDTA should be used in these ca- be a challenge, in that it almost always
and the administration of potent topical inside neutrophils with degenerate nuclei,
ses. causes tympanic membrane perforation
or systemic corticosteroids, to decrease attached to a large corneocyte in the middle.
inflammatory changes that may hinder (Diff Quik®, 1000x). n Underlying disease: otitis is always and otitis media and is caused by multi-
the healing of the ear canal. a complication of an underlying dis- drug resistant bacteria. Dogs with Pseu-
ease and if this is not identified and domonas otitis suffer from a severely
controlled, the ear disease will not purulent, erosive-ulcerative, extremely
Difficulties and particularities cure or will relapse frequently. Com- painful ear disease with a very strong
mon underlying diseases are atopic foul-smelling odour. Deep ear clean-
Frequent causes of treatment failure chlorhexidine, tris-EDTA (particularly in dermatitis, food allergy, foreign bod- ing, analgesics, corticosteroids (pred-
are: the case of Gram-negative bacteria), acids ies, ear canal masses (e.g. naso- nisolone 1-2mg/kg for 2 weeks, then
and/or alcohols. Topical treatment con- pharyngeal polyps in cats), parasites every 48h), topical and systemic antibi-
n Incorrect ear cleaning and poor owner
taining an antibiotic and a corticosteroid (Otodectes or Demodex), endocrine otics are needed for a minimum of 3-4
compliance: deep ear cleaning is very
should be applied after about one hour. disease and keratinization disorders. weeks. Consider referral to a specialist.
important in otitis. It should be per-
formed by the veterinarian, preferably In case of suspected low owner com-
under general anaesthesia and analge- pliance or pain on application of topical
sia, at the start of treatment and then medication, then a topical leave-on gel
daily by the owners. Use a disinfectant, with one week’s duration can be applied
cleaning and drying solution containing instead of eardrops and daily washing.

150 151
DISEASE FACT SHEETS

152
Internal medicine

153

DISEASE FACT SHEETS


Prevention of infectious
endocarditis
have a negative blood culture.
Luckily bacterial endocarditis is rare as it is potentially fatal.
n In dogs, the same bacteria are often
• In animals which are at risk from endocarditis, pre-operative antibiotic prophylaxis
is indicated. involved, as well as Escherichia coli or
anaerobic bacteria6. Bartonella may
• For treatment of infectious endocarditis, see Bacteraemia (sepsis), p.158. Antibiothe-
also play a role in the development of
DISEASE FACT SHEETS

DISEASE FACT SHEETS


rapy is indicated, based on a blood culture.
infectious endocarditis in dogs8.
Bacteria involved n Bacterial endocarditis is very difficult

© Rui Lemos Ferreira


to diagnose. The diagnosis is based on
Bacteria Prevalence a combination of major criteria (positive
blood cultures, echocardiographic signs
Streptococcus spp. +++ (45-50 %) of infectious endocarditis) and minor
criteria (predisposing cardiac factors, a
Staphylococcus spp. ++ (20 %) heart murmur suddenly appearing or
getting worse, fever, various immuno- Figure 1 - Endocarditis. Right parasternal
logical and microbiological phenome- view (five chamber long-axis) with vegetation
Escherichia coli + (10 %) on the septal aortic valve in a (febrile) boxer
na). with acute congestive heart failure associated
n All infectious sites where trauma of with severe aortic regurgitation.
Treatment recommendations the oropharyngeal, gastrointestinal or
urogenital mucous membranes occurs
Antibiotics that their platelet-aggregation properties
Bacteria Dosage Duration of treatment can lead to bacteraemia, which may lead
can be used
to bacterial endocarditis. Oral infections contribute to the development of en-
Amoxicillin ± 10 mg/kg/12h
Staphylococcus spp. An injection before in the context of severe periodontal docarditis, blood clots, coronary artery
gentamicina 8 mg/kg/8h
surgery or illness are the most studied scenario in occlusion and heart attacks in humans2.
Amoxicillin ± 10 mg/kg/12h oral treatment
Streptococcus spp. dogs. Periodontal disease, once estab- n In one study , 10% of the small dogs
2
clavulanate 12.5 mg/kg/12h
a Aminoglycosides
lished, provokes a discharge of endo- suffering from moderate to severe per-
are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).
toxins (LPS) and inflammatory cytokines iodontal disease had echocardiograph-
which can initiate and exacerbate the ic and systemic signs compatible with
Diagnostic approach outbreak of heart disease (atherogen- bacterial endocarditis. Over 80% of dogs
esis, thromboembolism). Bacteria from with a severe periodontal disease had at
n Bacterial endocarditis is a rare dis- heart diseases (hypertrophic cardiomy- dental plaque enter the blood stream and least one cardiac modification.
ease in dogs, but one which can be opathy, valve dysfunction) are consid-
life-threatening. Transient or persistent ered important risk factors.
bacteraemia may result in valvular le- n In humans, oral streptococci are in- Therapeutic choices
sions. volved in 25% of cases, streptococci of
n Prevention of bacteraemia, which may is recommended prior to any interven-
n The bacterium in question can be one a digestive origin in 20% of cases and
that is normally present in the mucous staphylococci in 15 to 30 % of cases lead to bacterial endocarditis, consists tion that is likely to facilitate the pas-
membranes of the ear, nose, throat (S. aureus and S. epidermidis essen- of eradicating all potential infectious sage of bacteria into the bloodstream.
(ENT) or digestive tract. Valvular dam- tially). It should be noted that 10 to entry sites, as previously noted. n According to the recommendations of

age and other congenital or acquired 20% of cases of infectious endocarditis n In this scenario, antibiotic prophylaxis AFSSAPS1 published in 2001 for human

154 155
Prevention of infectious endocarditis

medicine, standard prophylaxis of infec- treatment is implemented, consisting severe periodontal disease, compared
tious endocarditis requires a single dose of high-dose, long-term antibiotherapy to the rest of the population4. On the
of antibiotic administered orally one using amoxicillin combined with gen- other hand, a retrospective study of 76
hour before surgery, with a prescription tamicin or vancomycin, depending on dogs suffering from bacterial endocar-
of a 2 g dose of amoxicillin for an adult the bacteria involved. ditis did not establish an association be-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


and 50 mg/kg for a child. In the case of n Animals suffering from advanced tween bacterial endocarditis and a past
an allergic reaction to ß-lactams, clin- periodontal disease, with cardiac anom- history of infection or oral surgery9. As
damycin can be used. If prophylaxis alies (heart murmur, cardiac valve and for humans, in the absence of a consen-
must be administered parenterally, it is wall anomalies…) are at risk of bacte- sus, it would seem prudent to recom-
recommended to administer amoxicillin rial endocarditis. If such animals need mend antibiotic prophylaxis for bacterial
during the hour prior to the operation (in to undergo a dental or oral intervention, endocarditis in patients suffering from
a drip given for 30 minutes of 2 g IV for cardiovascular disease when they need
antibiotic prophylaxis is indicated with
an adult and 50mg/kg IV for a child, then to undergo invasive oral surgery, in par-
amoxicillin administered intravenously.
1g orally for the adult and 25 mg/kg for ticular in cases of advanced periodontal
Anti-infectious treatment consists of
a child, 6 hours later). disease.
high-dose, long-term antibiotherapy
Also, it seems prudent to consider that
n In humans, in the face of strong ev- using notably amoxicillin combined with
animals suffering from advanced per-
idence or the confirmed presence of gentamicin, to be adapted depending on
iodontal illness, with cardiac anoma-
bacterial endocarditis, anti-infectious the blood culture results7.
lies (heart murmur, heart wall or valve
anomalies...) are at-risk patients for
bacterial endocarditis. Animals suffering from advanced periodon-
Difficulties and particularities n In humans, infection prophylaxis in
tal disease and cardiac anomalies (e.g. myx-
omatous mitral valve disease) are at risk of
n In humans, the need for antibiotic valves, or patients that need to undergo case of joint replacements is identical bacterial endocarditis.
prophylaxis in patients at risk of bacteri- periodontal (in particular periapical) or to that used for infectious endocarditis.
al endocarditis is controversial. Two re- implant surgery3,9. On the other hand,
cent meta-analyses revisited this issue antibiotic prophylaxis specific to bacte-
and confirmed certain contradictory as- rial endocarditis does not appear to be
pects, but nevertheless proposed some justified in patients undergoing surgery
recommendations. The effectiveness of of the urogenital or digestive tracts9.
antibiotic prophylaxis using penicillin n Recent veterinary studies illustrate
has not been demonstrated in patients this contradictory situation. An epide-
at risk from bacterial endocarditis5. miological study of around 60 000 dogs
However, such antibiotic prophylaxis is confirmed that the presence of severe
recommended in patients suffering from periodontal disease is significantly as-
underlying cardiac conditions and in the sociated with increased risks of cardio-
case of oral surgery. It seems prudent to vascular disease, such as bacterial en-
administer specific antibiotic prophylax- docarditis and cardiomyopathy. It showed
is in patients with a past history of bac- that the risk of bacterial endocarditis is
terial endocarditis, with prosthetic heart six times greater in dogs suffering from

156 157
Bacteraemia (sepsis)
Pathogen 2: Staphylococcus spp. (Gram-positive)
Bacteria involved 2,3,4

In vitro Treatment Sensitivity


Antibiotics that can be used and distribution
sensitivity choice
Bacteria Prevalence Reported associations 1 = nil
Amoxicillin + clavulanate 4 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Polymicrobial infections with 3 = average
Cefalexin / Cefazolin / Cefalothin / Cefadroxil 4
Gram-negative bacteria +++ canine (31-46%) Gram-negative and anaerobic bacteria 4 = good
(E.Coli most common) +++ feline (43%) are commonly associated with Marbofloxacina / Enrofloxacina,b 5 5 = excellent
gastrointestinal tract perforation Treatment
Pradofloxacin a,d 5 choice
Gram-positive bacteria
Infections arising from the respiratory,
(Staphylococcus spp. ++++ canine (36-68%)
genitourinary and gastrointestinal tract
Pathogen 3: Obligate anaerobes 1st line
and Streptococcus spp. +++ feline (45%)
typically involve Gram-negative bacteria In vitro Treatment
most common) Antibiotics that can be used 2nd line
sensitivity choice
Obligate anaerobes + canine (12-31%) Infections arising from the integument
(e.g. Clostridium spp.) + feline (12%) typically involve Gram-positive bacteria Amoxicillin 4 Last resort

Ampicillin 4
Excluded
for this
Antibiotics that can be used Clindamycin 4
indication
Amoxicillin + clavulanate 4-5
Pathogen 1: Escherichia coli (Gram-negative) Metronidazole 5
In vitro Treatment Sensitivity Pradofloxacin a,d 5
Antibiotics that can be used and distribution
sensitivity choice
1 = nil Note: In vitro sensitivities are estimates based on data2,3,8,9; sensitivities may vary locally.
Amoxicillin 3 2 = weak a Avoid use in growing dogs of large breeds.
3 = average
Amoxicillin + clavulanate 3 b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
4 = good
c Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Marbofloxacina / Enrofloxacina,b 4 5 = excellent
www.iris-kidney.com/education/prevention.html).
Treatment d
Cefalexin 2 choice Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if
a narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
Gentamicin c 3-4
1st line
Pradofloxacina,d 4
Note: In vitro sensitivities are estimates based on data2,3,8,9; sensitivities may vary locally. 2nd line

a Avoid
Last resort
use in growing dogs of large breeds.
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not
exceed 5 mg/kg. Excluded
c Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal
for this
indication
dysfunction (see www.iris-kidney.com/education/prevention.html).
d
Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if
a narrower spectrum antibiotic cannot be used (based on sensitivity testing results).

158 159
Bacteraemia (sepsis)

Therapeutic approach Treatment recommendations


n Non-antibiotic treatment:
• Identification of the source of bacterial infection and surgical debridement or re-
Sample for blood and urine culture and cytology section (where possible) are the priorities of treatment, once the patient has been
DISEASE FACT SHEETS

DISEASE FACT SHEETS


stabilised.
• Shock, acid-base and electrolyte derangements with appropriate fluid resuscitation
and replacement must be addressed.
• Analgesia, oxygen therapy and vasopressors may be indicated.
Empirical emergency Ampicillin/amoxicillin + marbofloxacin/enrofloxacin
treatment Clindamycin + marbofloxacin/enrofloxacin First choice antibiotic combination (empirical/with C&AST)
while awaiting Amoxicillin+clavulanate + marbofloxacin/enrofloxacin Ampicillin/amoxicillin + fluoroquinolone, clindamycin + fluoroquinolone, or amoxicillin +
results clavulanate + fluoroquinolone, using the following doses:
Broad-spectrum Antibiotics that can be
combination therapy Ampicillin + gentamicin Pathogen involved Dosage Duration of treatment
used in combination
10-20 mg/kg/8h IV,
Ampicillin (sodium) not recommended
Gram-positive aerobic for oral use
bacteria e.g.
Results of culture and sensitivity Staphylococcus spp. Amoxicillin 10-25 mg/kg/8h IV, PO
IV
De-escalate if possible (avoid associations) Streptococcus spp.
until patient is stable,
Continue antibiotherapy for 4 to 6 weeks Clindamycin 5.5-11 mg/kg/12h IV, PO hydrated and eating.
Anaerobic bacteria e.g.
Further treatment
Clostridium spp. 12.5-25 mg/kg/8-12h
Amoxicillin + clavulanate according to
IV, PO underlying disease.
Gram-negative aerobic
Obligate anaerobes bacteria e.g. Marbofloxacina 2 mg/kg/24h IV, PO
E. coli Staphylococcus spp. E. coli
(false negatives possible)
Enrofloxacina,b 5 mg/kg/24h IV, PO
Amoxicillin+clavulanate, Amoxicillin+clavulanate, Amoxicillin, ampicillin,
marbofloxacin, enrofloxacin cefalexin or other 1GC clindamycin
Second choice antibiotic combination (empirical/with C&AST)
Ampicillin + gentamicin, using the following doses:
Marbofloxacin, Amoxicillin + clavulanate,
Cefalexin Antibiotics that can be
enrofloxacin metronidazole Pathogen involved Dosage Duration of treatment
used in combination
10-20 mg/kg/8h IV, IV
Ampicillin (sodium) not recommended until patient is stable,
Pradofloxacin Pradofloxacin Pradofloxacin Gram-positive aerobic, for oral use hydrated and eating.
Gram-negative aerobic
5-10 mg/kg/24h slow IV Further treatment
and anaerobic bacteria
Gentamicinc (over 30minutes), according to
IM, SC underlying disease.

For footnotes, see at beginning of the chapter.

160 161
Bacteraemia (sepsis)

basis of sensitivity results and clinical similar wide spectrum of activity as the
Diagnostic approach response. use of enrofloxacin is generally avoided
n Bacteraemia is the presence of viable systemic complications e.g. acid-base • Treatment with amoxicillin+/-clavula- in cats where alternative fluoroquinolo-
bacteria within the bloodstream. Bac- disturbances, disseminated intravascu- nate and enrofloxacin has been reported nes exist (e.g. marbofloxacin).
teraemia may be associated with the lar coagulopathy (DIC): to be the most effective combination • Pradofloxacin provides four-quad-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


development of a systemic inflamma- • haematology: neutrophilia +/- left in cats and dogs with bacteraemia but rant cover as monotherapy, however it
tory response leading to sepsis, severe shift, neutropenia, monocytosis, mild likely reflects commonly chosen antibi- is not available in a parenteral formula
sepsis or septic shock. Infections are non-regenerative anaemia, thrombocy- otics in practice4. The alternative combi- and there are regional variations in the
more commonly due to a single bacteri- topenia, nations detailed in the tables provide a product license for use in dogs.
al species (70-88% of canine and feline
• serum biochemistry: hypoalbumi-
infections)2,4. Presenting signs are var-
naemia, hyperbilirubinaemia, electrolyte
iable depending upon the primary site
disturbances, hypocalcaemia, raised
of infection, involvement of other organ Procedure for obtaining blood cultures
ALKP, hypo/hyperglycaemia, azotaemia,
systems and development of shock.
• blood gas analysis: metabolic acidae- • Clip coat over venepuncture site e.g. over jugular and saphenous
n The diagnosis is confirmed by mia, veins.
• blood culture for aerobic and anaero- • urinalysis: include urine culture, • Prepare skin for aseptic venepuncture
bic bacteria (see next page), (e.g. clean skin with 10% povidone iodine
• coagulation tests: prolonged APTT
• blood cytology - Gram staining may swabbing concentrically from the centre
and PT and raised D-Dimers in DIC;
aid empirical treatment choices, outwards, allow to dry).
TEG (hypercoagulable> hypocoagulable
• culture and cytology of samples of in sepsis)7, • Clean stopper of culture tube/bottle with
tissue/fluid from primary site of infec- 70% alcohol; allow to dry.
• blood pressure measurement, pulse
tion if accessible. oximetry, • Perform venipuncture using sterile gloves
to palpate the vein.
n Adjunctive diagnostics to localise the • imaging: abdominal ultrasound, echo-
primary site of infection and assess for cardiography, thoracic radiography/CT. • Inoculate blood culture bottle without
changing the needle.
• Space cultures based on illness severity before starting antimicrobial therapy
Reasoning (acute febrile illness 2 sets from separate sites over 10 minutes to allow anti-
microbials to be started quickly; acute endocarditis 3 sets from 3 separate sites
n Antibiotic therapy cannot be delayed cover a broad spectrum (i.e. aerobic, collected within 1-2 hours). Adapted from Sykes and Rankin, 2014.
until culture and sensitivity test results anaerobic, Gram-positive and negative).
are available in patients suspected to be Consider the likely source of infection
bacteraemic, due to the high risk of de- and expected bacteria, penetration of
velopment of sepsis, severe sepsis and the antibiotics, typical susceptibility pat- Difficulties and particularities
septic shock, each respectively associ- terns and prior antibiosis. n Bacteraemia may occur when a fo- n Diseases associated with acute bac-
ated with higher morbidity and mortality. n Combination therapy is initially rec- cal infection overwhelms local immune teraemia include prostatitis, pyometra,
n Initial empirical treatment should be ommended to provide a broad spectrum defences, the patient is immunocom- gastrointestinal rupture and peritonitis,
bactericidal, administered intravenously and de-escalation to narrower spectrum promised or there is a virulent microor- pancreatitis and pyelonephritis. Chronic
(with a loading dose if appropriate) and drug(s) should be carried out on the ganism. bacteraemia may occur with infections

162 163
Bacteraemia (sepsis)

due to Bartonella spp. and Haemoplas- before culture and sensitivity results
mas, which may only be identifiable us- are known is incompletely understood,
ing PCR techniques. due to the complexity of management of
n Identification and aggressive man- septic patients1,6,10.
agement of septic shock is critical in the n Duration of treatment is determined
DISEASE FACT SHEETS

DISEASE FACT SHEETS


successful management of bacteraemic by the underlying cause of bacteraemia
patients; goal-directed fluid resuscita- and commonly prolonged where sur-
tion11, infection source identification and gical resection of the infection source
control are essential alongside early an- is impossible e.g. endocarditis ≥ 4-6
tibiosis. weeks, however currently recommen-
n Prior treatment with antibiotics dations are often based on best clinical
should be considered and alternative judgement, lacking an evidence base or
antibiotics used to reduce the chance the ability to use biomarkers to guide
of selecting inappropriate antimicrobi- withdrawal of antibiotics compared to
als. The impact of inappropriate therapy human medicine6.

Identification and aggressive management of septic shock is critical in the successful manage-
ment of bacteraemic patients; goal-directed fluid resuscitation, infection source identification
and control are essential alongside early antibiosis.

2
164 165
Rare mycobacterial
infections
The relevant legislation in each country should be adhered to enabling The presence of acid-fast bacilli, often growth is evident, nucleic-acids based-
appropriate zoonotic risk information to be given to owners, in particular within macrophages, suggests myco- methods or mycolic acid analysis with
regarding M. tuberculosis. bacterial infection, but it is not specific high-performance liquid chromatogra-
Following diagnosis the case should be managed in conjunction with an to Mycobacterium tuberculosis complex phy or mass spectrometry (MALDI-TOF)
appropriate specialist and microbiologist. (MTBC) organisms. Some mycobacteri- may be used to determine if the organ-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


al strains are unculturable. MTBC and ism belongs to MTBC. Real-time PCR
Bacteria involved M. avium-intracellulare complex (MAC) is available for the rapid identification
organisms are slow growing (several of mycobacterial infection and for the
Major reservoirs Human health weeks) and culture is the gold-standard differentiation of MTBC organisms from
Bacteria* Host (pets)
(Geographic distribution) Significance method because it allows mycobacteria other mycobacteria.
Mycobacterium tuberculosis complex (MTBC)** typing and susceptibility testing. Once
Humans (USA, Africa, Primary cause of
M. tuberculosis Dogs
southern Europe) tuberculosis in humans.

M. bovis Cats, rarely dogs


South-western England Rare cause of Reasoning
and Wales tuberculosis in humans.
n In many countries, euthanasia of infected Following diagnosis, the case should be
South-western Scotland,
Very rare cause of animals is recommended taking into managed in conjunction with an appro-
M. microti Cats, very rarely dogs northern and southern
tuberculosis in humans. account the zoonotic risk and prognosis. priate specialist and microbiologist.
England, western Europe
Mycobacterium avium-intracellulare complex (MAC)
Humans acquire
infection from
Environmental
M. avium / environment. Direct
Cats and dogs saprophytes (worldwide,
M. intracellulare transmission from
eastern England)
animals has not been
described.
* This table is not exhaustive; other types of mycobacterial infections exist.
** Transmission to humans may be possible.

Diagnostic approach
n The diagnosis of mycobacterial infec- and peripheral lymphadenopathy. Occa-
tions is based on the suggestive history, sionally, abdominal, bone and systemic
clinical signs and radiographic abnor- dissemination occurs4,9.
malities, combined with the results of
the histopathology, molecular tests and n Several methods are available for the
culture. M. tuberculosis infections cause microbiological diagnosis of mycobacte-
pneumonia and tracheobronchial lym- rial infections in dogs and cats. Acid-fast
phadenopathy but rarely disseminate to staining can be applied to tissue aspi-
the CNS, liver or kidney; while M. bovis rates, buffy coat smears, body fluids,
and M. microti cause cutaneous lesions airway lavage specimens and biopsies.

166 167
Vector-borne bacterial
infections
Bacteria involved Treatment recommendations
Geographic Antibiotics that
Diagnostic Pathogen involved Dosage Duration of treatment
Bacteria Vector Hosts Clinical signs distribution can be used
method
in Europe*
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Borrelia burgdorferi s.l. 28 days
95% subclinical or Clinical signs and
transient fever, lameness, exclusion of other
Borrelia swollen joints, fatigue, diagnoses, response Bartonella spp. 28 days
Dogs Throughout to therapy. Serology
burgdoferi Ixodes spp. anorexia. Rare chronic
(cats) Europe and PCR from skin
sensu lato cases of joint disease Ehrlichia canis 28 days
or immune-mediated or synovia may be Doxycycline 10 mg/kg/12-24h PO
nephropathy. supportive.
A. phagocytophylum
Bartonella Usually asymptomatic. Anaplasma 15-20 days
henselae Cats Possibly fever, gingivitis, A. platys 8-10 days
Bartonella (dogs) lymphadenopathy, Histology,
clarridgeiae Ctenocephalides UTI, uveitis. Throughout immuno- Rickettsia spp. 7 days
Bartonella felis felis Asymptomatic, Europe histochemistry,
vinsonii Dogs transient fever, serology, PCR.
subsp. (cats) endocarditis,
Clinically asymptomatic seropositive animals should not be treated with
berkhoggii granulomatous lesions antibiotics, as very often seropositivity derives from contact or past infec-
Monocytic ehrlichiosis.
tion (not necessarily current or active disease). Indeed the percentage of
Mainly seropositive dogs can be very high in endemic areas for most of the bacte-
Ehrlichia Rhipicephalus Lethargy, anorexia, weight
Dogs southern
canis sanguineus loss, anaemia, petechiae,
Europe Clinical rial vector-borne diseases.
pancytopenia. presentation, PCR,
Anaplasma
phagocy- Ixodes spp.
Granulocytic
ehrlichiosis. Acute fever, Throughout
blood smear for
A. phagocytophylum
Diagnostic approach
tophylum lethargy, anorexia. Europe only,
Dogs (cats) n The diagnosis of vector-borne bacte-
Infectious cyclic (serology).
Mainly rial diseases is not always easy. There
Anaplasma Rhipicephalus thrombocytopenia and southern
platys sanguineus fever (every 1-2 weeks). Europe
are only a few specific clinical signs and
Fever, lethargy, anorexia, clinicopathological abnormalities, such
Rickettsia stiff gait, myalgia, Mediterranean as thrombocytopenia in ehrlichiosis and
Ticks Dogs
conorii lymphadenopathy, countries anaplasmosis. Co-infections are not in-
dermal necrosis.
frequent and make the diagnosis even
Experimental: subclinical PCR, (Serology).
more challenging. Evidence of arthro-

© Salvador Cervantes
Cats illness in cats with an
Rickettsia Ctenocephalides Throughout pod bites together with a combination
and incubation period of 2–4
felis felis felis Europe
dogs months. Natural infection of multiple tests for the same agent or
in cats and dogs: unknown. for multiple agents is usually necessary.
* according to ESCCAP (Control of vector-borne diseases in dogs and cats, 2012). A positive serology test is not diagnos-
tic of the disease and is only indicative
Possible associations: of contact. In endemic areas there are
Figure 1 - Numerous female ticks, engorged
Ehrlichia, Anaplasma, Borrelia, Bartonella and Rickettsia may be associated with many asymptomatic seropositive ani- with blood, on the pinna of a dog.
each other or with Leishmania and/or Babesia. mals. Two or more quantitative serology

168 169
Vector-borne bacterial infections

tests some weeks apart to evaluate IgG Collars should be applied on dogs sev-
antibody kinetics may be necessary to eral days prior to exposure to the para-
assess the patient’s infection status. sites and their efficacy duration can be
On the other hand, recently infected reduced as well by water immersion.
animals may show clinical signs but n Vector control is also very important
DISEASE FACT SHEETS

DISEASE FACT SHEETS


may not yet have seroconverted. Blood as many of these micro-organisms can
smears can be useful in A. phagocy-

© Maruska Suárez
be transmitted to human beings and
tophilum infections, where morulae can cause dangerous diseases.
be seen in platelets in about 60% of the
n The geographical distribution of vec-
cases, but not for E. canis and A. platys.
tors is changing, it is therefore increas-
PCR is useful to identify bacterial DNA
ingly important to protect pets from an
in patients, but this does not mean that Figure 2 - Petechiae in a dog affected with extended spectrum of parasites and for
the microorganisms are viable and ac- Ehrlichia canis.
a longer period of time (ideally all year
tively causing the disease. Whole blood
round). Fleas in particular are underes-
in EDTA is the preferred sample mate- preferable in borreliosis and skin alone
timated as vectors, and repellent flea
rial for Ehrlichia, Anaplasma and Bar- for rickettsiosis. Response to treatment
control products should be applied to

© Salvador Cervantes
tonella, while synovial fluid or skin are will confirm the diagnosis in many cases.
every animal (whether indoors or out-
doors) all year round.
Reasoning n If patients do not respond rapidly to
treatment, then other co-infections
n Even if other antibiotics are effective, improvement is expected within a few
or diseases with similar clinical signs
doxycycline is recommended, because days but the antibody titre can remain
should be investigated.
it is active in all bacterial vector-borne high for a long period of time. For this Figure 3 - Ehrlichia morula in a blood smear
reason, treatment should be aimed at n Borrelia vaccination is controversial from a dog.
diseases and co-infections are very
frequent. Treatment of bacterial vector- negative PCR results. and experts generally do not advise it.
borne diseases may be a challenge, as it n Depending on the pathogens con-
is not always possible to achieve a com- cerned, secondary choices include
plete elimination of the pathogen even amoxicillin +/- clavulanate, marbofloxacin,
in the case of a clinical cure. Clinical enrofloxacin and chloramphenicol.

Difficulties and particularities


n Prevention of transmission of vec- usually contain pyrethroids, such as
tor-borne disease is extremely impor- permethrin, flumethrin or deltamethrin
tant. As some of the vector parasites, (collars or spot-ons). Spot-ons should
such as fleas and certain ticks, trans- be applied at regular interval and as per
mit the pathogens almost immediately label instructions and frequent bathing
when they bite, a repellent should be should be avoided in these animals when
chosen to avoid a blood meal. These appropriate evidence is not available.

170 171
Haemotropic mycoplasmosis

Bacteria involved Diagnostic approach


Mycoplasma haemofelis. n Feline haemoplasmas or haemotropic
mycoplasmas are epicellular Gram-neg-
Antibiotics that can be used ative organisms. They produce different
DISEASE FACT SHEETS

DISEASE FACT SHEETS


degrees of anaemia and illness in cats.
Pathogen 1: Mycoplasma haemofelis Sensitivity Between 14-27% of cats with regener-
and distribution
1 = nil
ative anaemia were found positive for
In vitro Intracellular Treatment haemoplasmosis2,3. Four distinct hae-
Antibiotics that can be used 2 = weak
sensitivity distribution choice

© Salvador Cervantes
3 = average moplasmas have been detected in cats.
Doxycycline 5 5 4 = good M. haemofelis is the most pathogenic
Not routinely 5 = excellent
Clindamycin available 5 and usually causes haemolytic anaemia
Treatment
Pradofloxacina 5 5 choice and can be fatal, while other mycoplas-
mas can induce anaemia in immuno-
Amoxicillin + clavulanate 1 2 1st line
compromised cats such as those infected
Cefalexin 1 2 by FIV or FeLV. Figure 1- Cytology of Mycoplasmas (arrows)
2nd line in a blood smear (Diff-Quik)®.
a Pradofloxacin is a last resort choice due to its very extended spectrum of activity n Clinical signs depend on the level of
and should only be used if a narrower spectrum antibiotic cannot be used (based on
sensitivity testing results). Last resort anaemia (e.g. pale mucous membranes,
tachypnoea, tachycardia…) and are com- is based on identification of the haemo-
Excluded
for this monly accompanied by fever. Diagnosis plasma in a blood smear and using PCR.
indication

Treatment recommendations Reasoning


First choice antibiotic n Infections with haemotropic mycoplasmas severely ill cats. Fluoroquinolones are
Antibiotics that are not easily cleared, and long term useful in solving clinical signs but with
Pathogen involved Dosage Duration of treatment
can be used treatments with appropriate antibiotics the exception of pradofloxacin, they can-
Mycoplasma (doxycycline, fluoroquinolones) are needed. not clear the infection1.
Doxycycline 10 mg/kg/24h At least 21 days*
haemofelis Parenteral treatment may be needed in
Second choice antibiotic (if first-choice antibiotic is ineffective)
Pathogen involved
Antibiotics that
Dosage Duration of treatment Difficulties and particularities
can be used
n Sometimes a course of corticosteroids anaemia. Prednisolone (1mg/kg PO q 24h)
Clindamycin 5.5-11 mg/kg/12h PO should be added to treatment with anti- or methylprednisolone are preferred.
Mycoplasma
At least 21 days*
haemofelis
5 mg/kg/24h PO
mycoplasmal antibiotherapy, in order to The owners should be informed about
Pradofloxacina
reduce the immune-mediated haemolytic the risk and benefits of this strategy.
* PCR-guided treatment cessation at 3-4 weeks.
a Pradofloxacin
is a last resort choice due to its very extended spectrum of activity and should only be used if a
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).

172 173
Feline toxoplasmosis

Pathogen involved Therapeutic approach


Toxoplasma gondii. Clinical signs consistent
with toxoplasmosis
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Antibiotics that can be used Clindamycin

Pathogen 1: Toxoplasma gondii Sensitivity


and distribution
Trimethoprim sulfonamides
In vitro Intracellular Treatment 1 = nil
Antibiotics that can be used 2 = weak
sensitivity distribution choice
3 = average
Clindamycin 4-5 4 4 = good Doxycycline
5 = excellent
Trimethoprim sulfonamides a 4-5 5
Treatment
Doxycycline Not routinely
available 4 choice
Diagnostic approach
a Avoid
use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and 1 line
st

nephrotoxicity. Schirmer tear testing is recommended if use > 3 weeks4. n Toxoplasmosis involves the central a 2-3 weeks’ period, combined with
nervous system, the lungs, the liver, the clinical signs and ideally an appropriate
2nd line
pancreas and the striated muscle. It is response to anti-Toxoplasma treat-
Last resort more common in immunocompromised ment2. The identification of the parasite
cats (e.g. FIV, immunomodulatory treat- in cytology/biopsy or PCR techniques
Excluded ment such as ciclosporin). (e.g. muscle biopsy, CSF sample or fluid
for this
indication n Typical clinical signs are: fever, pneu- from bronchoalveolar lavage) can also
monia, icterus, abdominal discomfort, be useful for the diagnosis of toxoplas-
Treatment recommendations dyspnoea, ascites, pancreatitis and mosis.
mesenteric lymphadenopathy3,5. Toxo-
First choice antibiotic
plasma can cause diarrhoea but usually
Antibiotics that is self-limiting and resolves in more or
Pathogen involved Dosage Duration of treatment
can be used less 2 weeks. In case of CNS involve-
Toxoplasma Clindamycin 11 mg/kg/12h At least 21 days
ment, multifocal neurological clinical
signs may be present, including ataxia,
blindness, seizures, depression, aniso-
Second choice antibiotic coria, nystagmus, head tilt and abnor-

© Salvador Cervantes
mal behaviour1,3.
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used n The diagnosis may be challenging.
Trimethoprim Serology (IFA or ELISA) to determine
Toxoplasma 15 mg/kg/12h At least 21 days
sulfonamidesa IgM or/and IgG titres against Toxo-
a Avoid
plasma are commonly used. Diagno-
use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks4. sis is based on IgM titres above 1:64 Figure 1 - Uveitis in a cat due to Toxoplasmosis.
or a fourfold increase in IgG titres over

174 175
Feline toxoplasmosis

Reasoning Clinical signs compatible with


n It is impossible to completely elimi- informed that treatment may not work active Toxoplasma infection
nate Toxoplasma from an infected cat. or may require more time. Drugs such
The aim of the treatment is therefore to as trimethoprim sulfonamides have
DISEASE FACT SHEETS

DISEASE FACT SHEETS


resolve the clinical signs. Clindamycin been used for this infection but it is im-
is the treatment of choice for toxoplas- portant to find an oral formula adapted Start clindamycin
mosis but in neurological cases may not
work well, and owners of cats diagnosed
for cats as this combination is especially
distasteful for cats.
+
with neurological toxoplasma should be Serum sample for IgM & IgG
Biopsy, cytology, PCR

Difficulties and particularities


n Oral clindamycin can cause anorexia, the same animals. The side effects stop
vomiting, and diarrhoea in dogs and soon after the dose is reduced or thera- Toxoplasmosis confirmed?
cats, especially at higher doses. These py is discontinued. Some clinicians use No Yes
side effects appear to be related to local probiotics with success during treat-
GI irritation, because parenteral therapy ment when patients develop diarrhoea
at similar doses does not cause them in to avoid stopping antibiotic therapy. Has the patient improved? Continue clindamycin until
clinical signs are resolved
No Yes

Stop clindamycin Continue clindamycin

+ +
Re-evaluate Re-evaluate for other diseases
responding to clindamycin.
Repeat IgG & IgM after 3 weeks

Figure 2 - Clinical approach to Feline Toxoplasmosis.

176 177
Pyrexia of unknown origiN
In case of pyrexia of unknown origin, empirical antibiotic therapy is rarely
indicated and should not substitute a thorough work-up. Table 1 - Staged diagnostic approach to pyrexia of unknown origin in cats and dogs5,6
In dogs, in 80% of cases the cause is not bacterial. Stage 1
• Take a thorough history (vaccination history, travel history, flea and tick control,
Diagnostic approach
DISEASE FACT SHEETS

DISEASE FACT SHEETS


indoor/outdoor status, contact with other animals. Cats: hunting behaviour,
cat fights).
n Pyrexia or fever of unknown ori-
gin (PUO) is defined as fever that does • Stop all medications to rule out drug-induced fever (72h is enough; penicillins,
not resolve spontaneously, does not tetracyclines, sulfonamides & levamisole are more commonly related with
respond to antibiotic therapy and for drug-related fever).
which the diagnosis remains uncertain • Perform a meticulous physical examination, including fundic and neurologic
after an initial diagnostic workup3. examination. Loss of rib spring may be a sign of a cranial mediastinal mass,

© Salvador Cervantes
lameness may indicate septic arthritis, enlarged lymph notes may indicate
n Empirical antibiotic therapy is not in-
infection (Figure 4), while cats with FIP may have ophthalmic alterations.
dicated in the majority of cases of PUO
without conducting a thorough diagnostic • Obtain samples for CBC, blood smear and serum chemistry profile. Save
work-up first to screen the patients for in- serum for serology or other testing.
flammatory/immune-mediated diseas- • Conduct a complete urinalysis, cytology and urine culture (even if urine cytology
es, neoplasia and infectious diseases. is negative). Submit a sample for UPC ratio if proteinuria and inactive sediment
Figure 1 - Chronic uveitis due to Toxoplasma. are present.
• Cats: test for FeLV and FIV. Dogs: test for vector-borne diseases (see
n In three retrospective studies investi- Vector-borne bacterial infections, p.168).
gating unexplained fever in dogs, the most • Conduct faecal centrifugation and faecal cytology (if neutrophils are detected
prevalent diseases were non-infectious then do a faecal culture to rule out Campylobacter and Salmonella. If clostridia
inflammatory conditions. Infectious caus- are recognized in cytology, perform a entorotoxigenic PCR test).
es were only diagnosed in 16% to 18% of • Consider thoracic radiographs (especially if abnormal auscultation sounds are
dogs1,2,4. detected or if rib spring is negative) and abdominal ultrasonography.
n While in cats, fevers are common, • Consider trial antibiotics if bacterial infection is suspected (e.g. doxycycline if
there are no retrospective studies. Most mycoplasmosis or ehrlichiosis is suspected or amoxicillin+clavulanate if
diseases associated with PUO in cats pyelonephritis is suspected).
are infectious8, but rarely bacterial. In If necessary, proceed to stage 2.
© Salvador Cervantes

cats, neoplasia is a less common cause


of PUO, and PUO due to immune-medi-
ated disease is rare10.
n PUO in cats is always a challenge. Usually
body temperatures between 39.5 - 41.1ºC
Figure 2 - FIP (wet form). Before a wet form (103-106ºF) are considered true pyrexia.
is detected some cats may have fever for
weeks. These cases can be very challenging.

178 179
Pyrexia of unknown origin

Table 1 (continued) Reasoning


Stage 2
n In case of pyrexia of unknown origin,
Repeat stage 1, tests as indicated.
empirical antibiotic therapy is rarely in-
• Obtain thoracic and abdominal radiographs if not obtained in stage 1.
dicated.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


• Conduct echocardiography if a heart murmur is present.
n However, if antibiotics are given to
• Perform fine-needle aspiration with cytology of masses, lymph nodes, and

© Salvador Cervantes
a patient with unexplained fever, care
fluids (cyst, pleural, peritoneal).
should be taken to obtain adequate
• Conduct blood culture. samples (e.g. bacterial culture on blood/
• Perform arthrocentesis. urine/tissue/fluid, samples for PCR
• Conduct bone marrow aspiration if warranted by CBC results (e.g. abnormal testing for certain pathogens) prior to
shape, size or numbers in blood cells). treatment.
Figure 3 - A cat with fever. Cold pads and IV
• Conduct serology for infectious diseases (e.g. IgG & IgM Toxoplasma titres in n Infectious conditions that have been fluids are applied.
cats). identified in dogs with fever include en-
• Obtain long bone and joint radiographs. docarditis, sepsis, pneumonia, abscess, n Severe hyperthermia will require
• Conduct an immune panel if indicated (e.g. species-specific Coomb’s Test, discospondylitis, pyothorax, osteomyeli- some kind of treatment, a fan directed
antinuclear antibody determination). tis and anaplasmosis1,4. It is therefore to the cage or intravenous fluid admin-
If necessary, proceed to stage 3. impossible to make general antibiotic istration could be enough to reduce the
recommendations for all febrile patients. severity of the hyperthermia without
Stage 3 n Common non-infectious causes for using drugs. Empirical antibiotic therapy
Repeat stage 1 and 2 tests as indicated. PUO in dogs include immune-mediated should be based on the organ system
diseases, primary bone-marrow-disor- involved or the infectious agent suspect-
• Conduct echocardiography even if no murmur is present.
ders and neoplasia1,2,4. ed (Figure 3).
• Perform bone marrow aspiration even if CBC results are normal.
• Perform biopsy as indicated.
• Perform bronchoscopy and bronchoalveolar lavage as indicated.
• Conduct cerebrospinal fluid analysis.
• Perform dental radiography.
• Consider advanced imaging.
• Perform laparoscopy or thoracoscopy as indicated.
• Consider exploratory laparotomy.
Administer trial antibiotic or antifungal (if indicated) therapy.

180 181
Pyrexia of unknown origin

Table 2 - Causes of PUO in dogs and cats (in bold the most common causes) 5,6. Difficulties and particularities
Origin of fever Dogs Cats n Treatment failure is mainly linked to
Abscess, pyelonephritis, pyothorax, bacteraemia, osteomyelitis, the fact that the aetiology of fever is not
Bacterial infection (focal a bacterial infection in most cases of
DISEASE FACT SHEETS

DISEASE FACT SHEETS


discospondylitis, infective endocarditis, septic arthritis, septic
or systemic)
meningitis, prostatitis, stump pyometra, peritonitis PUO.
Canine distemper n Antibiotic treatment is not only rarely
Viral infection FeLV, FIV, FIP, FCV, FHV, FPV
Canine parvovirus
indicated, but may also mask clinical
Mycoplasmosis (haemotrophic and non-haemotrophic), signs. In one study, pre-treatment of
tuberculosis and other mycobacterial diseases, diseases caused
by L-form bacteria (e.g. cellulitis or synovitis secondary dogs with PUO prior to referral was even
Bacterial diseases to bite wounds or surgical incisions) linked to a longer time until a diagnosis
could be established in these patients

© Bianka Schulz
Bartonellosis, borreliosis,
brucellosis (12 versus 9 days)2.
Toxoplasmosis, neosporosis, leishmaniasis n The most likely reason why some an-
Protozoal infection imals with PUO remain without a diagno-
Babesiosis, hepatozoonosis Cytauxzoonosis
sis is due to limitations in the diagnostic
Figure 4 - A Magyar Viszla dog with PUO and
Non-infectious Pancreatitis, primary bone marrow disorders, lymphadenitis, work-up. If veterinarians prescribe an- enlarged lymph nodes. Cytology and culture
inflammatory diseases panniculitis, pansteatitis, granulomatosis tibiotics empirically, in dogs there is at of the lymph node revealed systemic fungal
Lymphoma, leukaemia, multiple myeloma, least an 80 % chance of treatment fail- infection.
Neoplasia ure because of the non-infectious aeti-
necrotic solid tumours, malignant histiocytosis
ology of the potential underlying diseases. n Although the use of NSAIDs may be
Rickettsial disease Ehrlichiosis, anaplasmosis
n Before starting treatment, the risk indicated, it is important to remember
Fungal disease Cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis and benefits should be evaluated. Tem- that animals receiving NSAIDs should
Polyarthritis, systemic lupus erythematosus, rheumatoid arthritis, peratures less than 41°C are unlikely to be normotensive and properly hydrat-
vasculitis, meningitis, steroid-responsive neutropenia and fever be harmful and may even be somewhat ed. NSAID treatments may also mask
Immune-mediated
diseases beneficial because they constitute a clinical signs that could help resolve the
Immune-mediated
haemolytic anaemia protective response. case3.

Portosystemic shunt, drug reaction, toxin, idiopathic causes


Miscellaneous
Shar-pei fever Hyperthyroidism

182 183
DISEASE FACT SHEETS

184
Ophthalmology

185

DISEASE FACT SHEETS


Conjunctivitis and keratitis

Not all cases of conjunctivitis are infected with bacteria. Antibiotics that can be used
Dogs (and cats)
Bacteria involved Pathogen 1: Staphylococcus spp.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Antibiotics that can be used In vitro Local Treatment Sensitivity
and distribution
Dogs as topicals sensitivity concentration choice
1 = nil
Fusidic acid 5 5 2 = weak
Prevalence Prevalence 3 = average
Bacteria Neomycin-bacitracin-polymyxin B 4 5
Conjunctivitis3,8 Ulcerative conjunctivitis8 4 = good
Chloramphenicol 5 5 5 = excellent
Staphylococcus spp. 40-47% 16% Treatment
Pathogen 2: Streptococcus spp. choice

Streptococcus spp. 23-26% 27% Antibiotics that can be used In vitro Local Treatment 1st line
as topicals sensitivity concentration choice
Escherichia coli 4% 16% Fusidic acid 3 5 2nd line

Neomycin-bacitracin-polymyxin B 4 5 Last resort


Chloramphenicol 5 5
Cats Excluded
for this
Bacteria* Prevalence5
Cats only indication

Pathogen 3: Chlamydophila spp.


Chlamydophila felis 66% In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice
Mycoplasma spp. 49% Not
Doxycyclinea 5
routinely
Aerobic bacteria Amoxicillin + clavulanateb available 4
39%
(Staphylococcus spp., Streptococcus spp. & Micrococcus spp.)
Pathogen 4: Mycoplasma spp.
* association with FHV is common.
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice
Doxycyclinea Not 5
routinely
Amoxicillin + clavulanateb available 4
Marbofloxacin 4 5
Not
Pradofloxacinc routinely 5
available
a Oral doxycycline is the treatment of choice in adults cats.
b Oral amoxicillin + clavulanate is the treatment of choice in kittens and nursing queens.
c Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).

186 187
Conjunctivitis and keratitis

Therapeutic approach Treatment recommendations


Dogs First choice antibiotic (whilst waiting for culture and sensitivity testing)
Antibiotics that
Corneal smear (cytology ± culture) Pathogen involved Dosage Duration of treatment
DISEASE FACT SHEETS

DISEASE FACT SHEETS


can be used
Fusidic acid
1-2 times/day
(eye drops/ointment)
Staphylococcus spp.
8-10 days
Staphylococcus/ Streptococcus spp.
Escherichia coli Neomycin - bacitracin
Streptococcus spp. 5-6 times/day
(Gram-negative rod) polymyxin (eye drops)
(Gram-positive cocci)
Chlamydophila spp. Doxycycline (oral) 10 mg/kg/24h 30 days4
Neomycin + bacitracin + Neomycin + bacitracin +
polymyxin B polymyxin B, Fucidic acid Mycoplasma spp.* Doxycycline (oral) 10 mg/kg/24h 2-4 weeks

Second choice antibiotic (following culture and sensitivity testing)


Chloramphenicol Chloramphenicol Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Staphylococcus spp. Chloramphenicol
2-3 times/day 8-10 days
Streptococcus spp. (eye drops)
Cats Mycoplasma spp.* Amoxicillin +
12.5-25 mg/kg/12h PO 30 days9
Chlamydophila spp. clavulanate (oral)
Corneal smear (cytology ± culture)*
* Mycoplasma spp. cannot be diagnosed using a corneal smear or the usual culturetechniques. For this pathogen,
PCR is the gold standard diagnostic test.

Chlamydophila
Staphylococcus/
Streptococcus spp. Diagnostic approach
(Gram-positive cocci) n Conjunctivitis is the inflammation of the and cats2,3,5. The clinical appearance of
Neomycin + bacitracin +
mucosal membrane that covers the cra- conjunctivitis includes hyperaemia, ocu-
Doxycycline nial pole of the eye while keratitis is the lar discharge (mucoid to mucopurulent),
polymyxin B, Fucidic acid
inflammation of the cornea; the inflam- chemosis and, in chronic cases, lym-
mation of both is called keratoconjunc- phoid follicles11.
tivitis. Not all conjunctivitis is infected
Amoxicillin + clavulanate Chloramphenicol with bacteria and the use of antibacte- n It is important to perform a correct and
rials in conjunctivitis cases should be systematic step-by-step ophthalmic ex-
reserved until infection has been con- amination in order to get the best sam-
* Mycoplasma spp. cannot be diagnosed using a corneal smear or the usual culture ples and reach the correct diagnosis.
techniques. For this pathogen, PCR is the gold standard diagnostic test.
firmed (cytology). The aetiology of bac-
terial conjunctivitis is different in dogs Prior to applying fluorescein, or ophthalmic

188 189
Conjunctivitis and keratitis

cleaners, a sample should be taken for third sample for viral and chlamydial/ drops are preferred. surgical repair of ulcers or perforations
cytology and culture. mycoplasmal DNA detection1,5. n In feline bacterial conjunctivitis, are needed without delay.
n Cytology samples must be stained using n In both species the inflammation may be chlamydial infections usually need
a rapid differentiating staining system (e.g. due to a systemic infection (e.g. FHV-1, oral doxycycline to clear the infection
Diff Quik®) and if inflammation is noticed Canine distemper…) or secondary to a completely6. If patients live in a multi-cat
DISEASE FACT SHEETS

DISEASE FACT SHEETS


then the second cytology sample should pre-existing cause (e.g. entropion, kera- household, all cats should be treated in
be stained using a Gram stain system. toconjunctivitis sicca…). After taking sam- order to avoid a carrier-state.
n Microbiology samples should be ples, perform a Schirmer’s tear test and n In recurrent or complicated cases
kept just in case culture is needed. follow-up to complete the ophthalmic (melting ulcers), besides a corneal
Probably only the severe and/or re- examination including the evaluation of smear, a culture and sensitivity test
peated conjunctivitis/keratitis cases the fundus (conjunctivitis may be just

© Salvador Cervantes
should always be performed. Pending
requires a culture and sensitivity test. the tip of the iceberg of many other oph- results, initial treatment with anticolla-
In cats, it is recommended to keep a thalmic diseases). genases (e.g. EDTA, acetylcysteine, au-
togenous serum), cyclopegics (e.g. atro-
pine in dogs and tropicamide in cats) and
empirical antibiotics (e.g. Gram-pos-
itive: tri-antibiotic solution eye drops, Figure 3 - Dog with a severe ulcerative ker-
Gram-negative: fluoroquinolone eye drops) atitis.
should be started. In some of these cases,

© Salvador Cervantes
Difficulties and particularities
n In both conjunctivitis and keratitis, the cat is FHV-1. Sometimes, antiviral
self-trauma should be prevented (e.g. therapy may be required (e.g. famci-
1 2 Elizabethan collar). The cornea should clovir 40 mg/kg PO q 8h or ganciclovir
Figures 1 & 2 - Cats with chlamydial conjunctivitis. The cat on the right has also FHV (in this case also be lubricated properly, limiting eye topically).
Rose Bengal staining has been applied in order to identify geographical ulcers commonly seen dryness and eyelid self-trauma. To avoid
in FHV infections). eye dryness, mucinomimetic therapy
with hyaluronic acid and/or carbomers
Reasoning is preferred7.

© Salvador Cervantes
n Antibiotic resistance is not a common
n In mild and superficial cases the top- n In canine bacterial conjunctivitis, if feature in conjunctivitis or keratitis. If
ical application of antibiotics allows a Gram-positive cocci are detected, neo- efficacy seems to be lacking, it is impor-
high local dose and a good penetration mycin-bacitracin-polymyxin B (tri-an- tant to check owner compliance, as ap-
in affected tissues. tibiotic solution), chloramphenicol or plying eye drops in a painful and non-co-
n In mild and superficial cases, carrying fusidic acid eye drops may be recom- operative patient may be a challenge. Figure 4 - Severe herpetic keratitis in a cat with
out a conjunctival+/-corneal smear and mended at least for 8-15 days. If Gram- n The most common cause of conjuncti- a secondary infection with Streptococcus spp.
Gram staining is preferable to an empirical negative bacteria are detected a tri-an- vitis, keratitis and keratoconjunctivitis in
choice of a broad-spectrum antibiotic. tibiotic solution or chloramphenicol eye

190 191
Infectious uveitis
• This chapter covers agents not treated in other parts of this book - not necessarily
the most commonly diagnosed. Antibiotics that can be used
Infectious uveitis is rarely caused by bacteria; therefore, antibiotics are Dogs
rarely indicated. Pathogen 1: Brucella canis
DISEASE FACT SHEETS

DISEASE FACT SHEETS


In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
Pathogens involved Doxycycline 5 4
1 = nil
2 = weak
3 = average
Streptomycin 5 2
4 = good
Dogs Enrofloxacin a 5 4 5 = excellent
Treatment
Pathogens Prevalence Rifampicin 5 4 choice
Trimethoprim sulfonamides b 2 5
All bacterial vector-borne pathogens* ++ (15 to 40 %) 1st line

Pathogen 2: Leptospira spp. 2nd line


Leishmania infantum ++ (15 to 40 %)
In vitro Tissue Treatment
Antibiotics that can be used Last resort
Leptospira spp. + (< 10-20 %) sensitivity distribution choice
Penicillin G 4 2-3 Excluded
Fungal pathogens (e.g. Cryptococcus spp., Histoplasma spp.,
+ (< 10-20 %) Amoxicillin / Ampicillin 4 2-3 for this
Coccidioides spp.) indication
Doxycycline 5 4
Brucella canis + (< 10-20 %)
Gentamicin c 4 2-3
Streptomycinc 4 2
a Avoiduse in growing dogs of large breeds.
Cats b Avoid use longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear
testing is recommended if use > 3 weeks8.
Pathogens Prevalence c Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).
FIP +++ (35 to 65 %)

Toxoplasma spp.** ++ (15 to 40 %)


Cats
FIV + (< 10-20 %) In cats, bacterial uveitis is extremely rare (see previous page).

FeLV + (< 10-20 %)

Fungal pathogens + (< 10-20 %)

* see Vector-borne bacterial infections, p.168.


** see Feline toxoplasmosis, p.174.

192 193
Infectious uveitis

Therapeutic approach Treatment recommendations


General & ophtalmic exam
First choice antibiotic if presence of pathogen confirmed
If uveitis is confirmed: Antibiotics that
Pathogen involved Dosage Duration of treatment
DISEASE FACT SHEETS

DISEASE FACT SHEETS


can be used
8 weeks
Doxycycline + 10 mg/kg/24h PO +
Brucella canis (with streptomycin inj.
streptomycin 20 mg/kg/24h IM
Blood tests (serology) Start topical corticoids every other week)
depending on local prevalence and mydriatics 25,000 – 40,000 units
Penicillin G
/kg/12h SC, IM, IV
Leptospira spp. 3 weeks
Ampicillin
22 mg/kg/8h SC, IM
(for leptospiraemia)
Treat according to diagnosis.
If no diagnosis is reached:
Second choice antibiotic if presence of pathogen confirmed
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Aqueocentesis to calculate C
Refer to Specialist value for suspected disease Rifampicin 7.5 mg/kg/24h As needed
Brucella canis
(see Figures 1 and 2) Enrofloxacina 10 mg/kg/24h 8 weeks

Doxycycline
Leptospira spp. 5 mg/kg/12h PO 3 weeks
(for kidney carrier state)
a Avoid use in growing dogs of large breeds.

Diagnostic approach
Aqueous Antibody Coefficient (C-value): n Anterior uveitis is the inflammation of
[Specific Ab concentration in aqueous humour] [Other agent Ab concentration in serum] the anterior uvea, the vascular layer of
[Specific Ab concentration in serum]
X [Other agent Ab concentration in aqueous humour]
the eye, composed of the iris and ciliary
body. Posterior uveitis means both cho-

© Salvador Cervantes
Specific Ab: e.g. against Toxoplasma roid and retina are affected, and when all
Other agent: e.g. feline panleukopenia virus areas are affected this is called panuvei-
tis. There are many possible causes of
If the C-value is <1, there is no local production of specific antibodies (Ab)
uveitis, but a bacterial infection is rare.
If the C-value is between 1-8, the local production of specific antibodies (Ab) is probable.
If the C-value is >8, there is a local production of specific antibodies (Ab) Depending on the geographical location
In this formula, specific Ab are the antibody titres against the disease which you are trying to rule out1,6. of the patient, the list of possible diag-
Figure 2 - Aqueocentesis is an easy tech-
Figure 1 - Aqueous Antibody Coefficient (C-value). nosis should be adapted (e.g. Brucella nique allowing the comparison of titres
canis infections are more common in between serum and aqueous humour. The
America than in Europe, Mediterranean needle should always be parallel to the iris.
areas are endemic for Leishmania spp.).

194 195
Infectious uveitis

n Some of the most common signs are: for the ocular signs is by comparing the see Figure 2). With these titres, the C-
lacrimation, photophobia, ocular pain, serum titres with aqueous titres for a value can be calculated as shown in Fig-
blepharospasm, chemosis, conjuncti- specific pathogen (by aqueocentesis, ure 1.
val and/or scleral redness, hypopyon,
hyphaema or fibrin flare at the anterior Reasoning
DISEASE FACT SHEETS

DISEASE FACT SHEETS


chamber, abnormal iris pigmentation,

© Salvador Cervantes
miosis and anisocoria. n The treatment of Brucella canis infec- n Treatment of Leptospira spp. infec-
tions rarely produces a total clearance tions is divided in two steps. The first step
n Brucella canis: The clinical signs of
of infection, despite high in vitro sensi- aims to eliminate bacteraemia, while the
Brucella infections are mostly related to
tivity. Long-term treatment is required. second step aims to clear the infection
reproductive abnormalities (abortions,
A combination of antibiotics is recom- from the kidney and remove the carrier
stillborn and neonatal mortality) and mended, e.g. tetracyclines (doxycycline state. Treatment with penicillin or ami-
testicular inflammation (epididymitis & Figure 3 - Cat with uveitis due to FeLV. or minocycline) with streptomycin. Oc- nopenicillins is usually recommended
orchitis)7. The non-reproductive signs Hyphaema and anisocoria are noted.
ular infections require even a longer to treat the leptospiraemia followed by
include splenomegaly, generalized lym- treatment with a combination of three or doxycycline to solve the carrier state5.
phadenopathy and there are some pa- epistaxis, widespread petechiae, icterus, four antibiotics, the doses in these cas- Aminoglycosides are no longer recom-
pers reporting discospondylitis, menin- intestinal intussusception, oliguria or es are higher and the course of treat- mended due to their potential nephro-
goencephalitis, osteomyelitis and poly- anuria. In subacute cases, these include ment is longer. toxicity.
arthritis. Ocular involvement is not rare fever, anorexia, vomiting, dehydration,
in Brucella infections in dogs, with an- polydipsia and polyuria, reluctance to
terior uveitis, chorioretinitis and optic move, paraspinal hyperesthesia caused by
Difficulties and particularities
neuritis. Diagnosis of Brucella infec- muscular, meningeal or renal inflam- n If brucellosis is suspected, special n In all cases of anterior uveitis, local
tions may be challenging. Haemato- mation, congested mucous membranes, measures should be taken to avoid hu- anti-inflammatories are recommended
logical and biochemical values are ei- petechial or ecchymotic haemorrhages, man transmission. The use of gloves for even when a diagnosis has not yet been
ther unaltered or nonspecific in canine conjunctivitis, uveitis, rhinitis, tonsillitis, sampling is highly recommended and reached, because of the risk of blind-
brucellosis. Hyperglobulinaemia (ß and oliguria or anuria, coughing or dyspnoea owners should be informed about the ness in cases of protracted inflamma-
γ) with concomitant hypoalbuminaemia and icterus. The most remarkable lab- zoonotic risk and the cost of long-term tion. In the absence of corneal ulcera-
has been the most consistent finding in oratory findings are leukocytosis and treatment with several annual checks to tion, topical 1% prednisolone or 0.1%
chronically infected dogs. Specific tests, thrombocytopenia while elevated liver monitor if the disease is under control. dexamethasone ophthalmic solutions
such as cytoplasmic antigen agar gel enzymes (ALT, AST, ALKP, LDH), azo- Immunocompromised owners (HIV in- are indicated, used up to 4 times dai-
immunodiffusion (CPAg-AGID) may be taemia and creatinine are commonly fection, chemotherapy...) must take ex- ly3. NSAID eye solutions may be used
of help2. detected. Urine specific gravity is usual- treme precautions to avoid infection. but they are more expensive and less
n Leptospirosis: Clinical signs may vary. ly below 1.029 and haematuria and pyu- n Leptospirosis is also a zoonotic dis-
potent than corticosteroids. NSAIDs
In acute cases, any of the following ria are common features. Proteinuria ease. Immunocompromised owners are should not be used parenterally or
signs can be found: fever 39.5-40 °C, and glycosuria (if present) are indicative at particular risk for severe infection; topically if hyphaema is present.
shivering, muscle tenderness, vomit- of tubular damage. therefore, if they live in an endemic area, n The pain associated with anterior
ing, prostration, dehydration, peripheral n Sometimes after a complete ophthal- their dogs should be screened serologi- uveitis, resulting from a spasm of the
vascular collapse, tachypnoea, rapid ir- mic exam and serum serology, diagno- cally for exposure and possible infection, ciliary muscle, can be treated with at-
regular pulse, poor capillary perfusion, sis cannot be reached. One way to find and their dogs should receive multiva- ropine 1% (initially 3 times daily)4.
haematemesis, haematochezia, melena, out if a systemic disease is responsible lent vaccination on a regular basis.

196 197
DISEASE FACT SHEETS

198
Digestive system

199

DISEASE FACT SHEETS


Common diarrhoea
in dogs and cats
2. Provide a bland, digestible diet. Pro- or ultrasound).
Bacteria involved biotics can be tried for gastrointestinal 6. At this stage, an antibiotic therapeu-
support. tic trial can be tried (using amoxicillin +
Bacteria are rarely the cause of gastroenteritis in cats and dogs, and antibiotic 3. If there is no improvement, perform clavulanate +/- metronidazole)
therapy is rarely justified. a complete work-up, including blood
DISEASE FACT SHEETS

DISEASE FACT SHEETS


7. If diagnostic imaging provides a sus-
work, urinalysis and faecal examination. picion of intestinal disease or an in-
Antibiotics that can be used If this allows a diagnosis to be reached, testinal tumour, then a laparotomy or
then treat accordingly. endoscopy is recommended to get ab-
n Most bacterial enteropathogens are n Bacteriological stool analysis is not
4. If food intolerance or allergy is sus- dominal samples. If possible, samples
associated with self-limiting diarrhoea, indicated as a first-line of action.
pected, consider an exclusion trial with should also be taken from the mesen-
and injudicious administration of anti- n Salmonella and Campylobacter are a novel or hydrolyzed protein diet. This teric lymph node, pancreas and liver.
microbials could be more harmful than well-documented zoonoses, but anti- usually gives a response in less than 2-3 n If the patient is not well, provide sup-
beneficial. microbial administration is not routinely weeks, although several authors rec- portive treatment and take faecal sam-
n Correct diagnosis is crucial prior to advocated in uncomplicated cases. For ommend 4-6 weeks before totally dis- ples for culture and/or PCR. Intravenous
initiating any antibiotic treatment as the more information, see Gastroenteritis carding food-related causes. fluid therapy and antibiotics may be in-
incorrect use of antibiotics may trigger a due to bacterial pathogens, p.204.
5. If there is no improvement, perform dicated if sepsis is present (see Bacter-
bacterial overgrowth.
imaging (abdominal radiographies and/ aemia (sepsis), p.158).

Diagnostic approach
n Gastroenteritis may be chronic or evaluation of patients for signs of sepsis
acute. Client history and clinical exami- (left shift, toxic changes in neutrophils)
nation are generally sufficient to estab- and to exclude metabolic diseases (e.g.
lish a diagnosis of common gastroen- renal or hepatic disease, pancreatitis,
teritis. The causes of gastroenteritis are hypoadrenocorticism) and viral (Parvovi-
numerous and diverse. However, bacte- rus, Coronavirus) or parasitic infections.
rial causes are rare and one of the least Abdominal ultrasound can be helpful to
important causes of gastroenteritis in rule out obstruction, masses, pancreati-
terms of prevalence. tis and involvement of other organs.
n Therefore, it is very important to follow n Only if a definitive diagnosis of bac-

© Salvador Cervantes
a systematic step-by-step work-up prior terial infection is reached, may antimi-
to any antibiotic treatment. Any viral, crobial treatment be justified in certain
parasitic, drug-induced, toxin-induced cases (see Gastroenteritis due to bacte-
and food-responsive causes should be rial pathogens, p.204).
ruled out. n If the patient is in good general con-

n In cases of acute diarrhoea with system- dition: Figure 1 - Giardia spp., a frequent non-bacterial cause of chronic gastroenteritis in dogs and cats.
ic illness complete blood work, urinaly- 1. Fast the patient for a short period
sis and faecal (parasitological and viral) (12-24h) and deworm. If there is vomit-
examination is indicated. This allows ing or retching, provide anti-emetics.

200 201
Common diarrhoea in dogs and cats

Reasoning
No Diarrhoea
n Most cases of uncomplicated acute n If dogs show fever and/or an inflam- More than 3 weeks? Yes Exclude:
• Pancreatitis
diarrhoea resolve within several days. matory leukogram with toxic changes or
• Hyperthyroidism
Supportive treatment should include if they do not improve with symptomatic Chronic diarrhoea
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Acute diarrhoea • Liver disease
fluid therapy to correct dehydration therapy, further work-up including fae- Is it the bowel? No • Hypoadrenocorticism
and electrolyte imbalances, anti-emet- cal analysis for enteric bacterial patho- Yes • Kidney disease
ics, analgesia and gastroprotectants as gens can be indicated. • Toxins
needed. • Drugs
Exclude:
• Enteric viruses
• Parasites Small bowel Large bowel
Difficulties and particularities • Food intolerance
• Drug-induced Exclude:
n Faecal culture or PCR should be patients). Results should be interpreted • Toxins Mal-digestion
performed if there are systemic signs with care. • EPI
Exclude:
of illness (fever, anorexia, abdominal n Treatment failure may reflect antimi- Mal-absorption • Parasites (Giardia)
pain, haemorrhagic diarrhoea), if other • Parasites (Giardia)
crobial resistance or persistence of clin- • IBD
• IBD
causes have been ruled out (see Figure ical signs due to another unidentified • Obstruction
• Obstruction
2). The interpretation of these results is cause. • Neoplasia
• Neoplasia
challenging, because the presence of • Lymphangectasia
n Antibiotics may have a negative im-
these bacteria is not synonymous with • Food allergy
infection. pact and may promote dysbacteriosis • Viruses
(e.g. C. difficile proliferation).
n PCR does not help to determine an-
tibiotic sensitivity. A positive result only n In case of infection with Campylobac-
Check for: Check for:
means the presence of the pathogen in ter or Salmonella injudicious antimicro- • Salmonella • E. coli- associated
the sample. The presence of these path- bial administration may prolong the car- • Campylobacter granulomatous colitis
(in Boxers and Bulldogs)
ogens in healthy and sick patients compli- rier state and contribute to antimicrobial • C. perfringens, C. difficile
cates the interpretation of the results. (For resistance. This is particularly true for
Figure 2 - It is very important to follow a systematic step-by-step work-up prior to any antibiotic
example, Salmonella spp. or Clostridi- animals with uncomplicated diarrhoea treatment.
um spp. may be present in a patient with living with immunocompromised indi-
chronic diarrhoea but, also, in healthy viduals in the same household.

202 203
Gastroenteritis due to bacterial pathogens
Campylobacter, Salmonella, Clostridium, E.coli

n Salmonella and Campylobacter are


Bacteria involved well-documented zoonoses, but anti-
microbial administration is not routinely
advocated in uncomplicated cases.
Bacteria Prevalence
n The relation between the presence of
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Campylobacter spp.
+ to ++++ an enteric bacterial pathogen to clin-
(highly variable) ical disease is not easy to establish,

© Salvador Cervantes
Salmonella spp.
+ to ++++ as most of these bacteria can also be
(highly variable) detected in clinically healthy animals.
Clostridium perfringens + to +++

Clostridium difficile + to ++
Figure 2 - Rectal cytology (Wright’s stain) of the
Escherichia coli Rare
same cat as in Figure 1. Clostridiosis induced by
(Boxer Granulomatous colitis) (in boxer-like breeds only) treatment with clindamycin for dental disease.

Antibiotics that can be used


In general, bacterial gastroenteritis produces systemic signs
n Antibiotic therapy is rarely justified in (e.g. fever, lethargy, abdominal discomfort).
GI disease.
n In general, bacterial gastroenteri-
tis produces systemic signs (e.g. fever,
lethargy, abdominal discomfort). Diagnostic approach
n Prior to antibiotic treatment, viral,
n In cases of acute diarrhoea with sys- n The most commonly identified enteric
parasitic, drug-induced, toxin-induced
temic illness complete blood work, uri- bacterial pathogens in dogs include
and food-responsive causes should be
nalysis, and faecal (parasitological and Clostridium difficile, Clostridium per-
ruled out in acute diarrhoea, and sys-
viral) examination is indicated. This al- fringens, Campylobacter spp., Salmo-
temic, small or large bowel causes in
lows evaluation of patients for signs of nella spp., and Escherichia coli associated
chronic diarrhoea (see Figure 2 of Com-
© Salvador Cervantes

sepsis (left shift, toxic changes in neu- with granulomatous colitis in Boxers.
mon diarrhoea in dogs and cats, p.203).
trophils) and to exclude metabolic dis- However, the causal relation between a
n Only if a definitive diagnosis of bac- eases (e.g. renal or hepatic disease,
terial infection is reached, may antimi- positive result for one of these bacterial
pancreatitis, hypoadrenocorticism) and
crobial treatment be justified in animals agents and clinical disease is not easy
viral (Parvovirus, Coronavirus) or para-
manifesting systemic signs of illness to establish in most cases, because
sitic infections. Abdominal ultrasound
(e.g. fever, lethargy, abdominal discom- can be helpful to rule out obstruction, these bacteria can also be detected in
Figure 1 - Clostridial diarrhoea (faeces from the
fort). same cat as in Fig 2). masses, pancreatitis, and involvement clinically healthy animals.
of other organs. n The methods for their identification are

204 205
Gastroenteritis due to bacterial pathogens
Campylobacter, Salmonella, Clostridium, E.coli

often complex to carry out and interpret: by ELISA or conventional PCR or quanti- if available, otherwise a combination of n E. coli
• Clostridium difficile can be identified tative PCR toxin gene detection; ampicillin and enrofloxacin has been For treatment of E.coli-induced granu-
by culture (specific media and anaerobic • Salmonella detection is done by spe- advocated for empirical treatment. lomatous colitis, fluoroquinolones are
culture), antigenic ELISA or Polymerase cific selective culture or by PCR; n Campylobacter the drug of choice. Although many strains
Chain Reaction (PCR) assays, in combi- Similarly, dogs testing positive for Cam- show resistance to this antimicro-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


• Campylobacter jejuni can be detect-
nation with toxin analysis by ELISA or ed by direct observation by cytological pylobacter spp. should only be treated bial class in vitro, most dogs respond
PCR; examination of stool samples, bacte- if they are febrile and show systemic in vivo. Note that treatment must be
• Clostridium perfringens presence can rial culture (special culture media and signs. In that case, erythromycin, azith- given for a full eight weeks, even if
be demonstrated by culture (anaerobic) culture under microaerophilia for 72 to romycin and fluoroquinolones have been clinical response is much faster17.
or PCR, in combination with toxin analysis 96h) or molecular techniques (PCR). proposed for treatment.

Difficulties and particularities


n Infection due to Clostridium, Cam- recent study has provided evidence
pylobacter or Salmonella is often that in canine acute haemorrhagic
self-limiting and resolves with support- diarrhoea syndrome (AHDS), antibiotics
ive treatment. Injudicious antimicrobial are rarely indicated30.
administration may prolong the carrier n C. difficile was not found to be an
state and contribute to antimicrobial important pathogen in dogs with acute
resistance. This is particularly true for haemorrhagic diarrhoea syndrome1.
animals with uncomplicated diarrhoea, However, patients with AHDS should be
creating an undue risk for any immuno- monitored closely for fever or inflam-
compromised members of the house- matory changes on their leukogram,
Figure 3 - Only systemically ill
animals with confirmed bac-
hold. because these might be indicators for
terial gastroenteritis should n Infection control measures and rec- bacterial translocation and sepsis re-
be treated with antibiotics. ommendations should be undertaken quiring antibiotic treatment (see Bacte-
due to the zoonotic nature of both infec- raemia (sepsis), p.158).
tions. Antibiotic treatment is an option
Reasoning for severely ill dogs and cats.
n Basic practices of isolation, with
proper cleaning and disinfection are the
n Clostridium erythromycin, metronidazole and tylosin n Treatment failures may reflect anti- mainstays of infection control. Spores of
In dogs with severe clinical signs, which are antimicrobials that were recom- microbial resistance, infection with a C. difficile and C. perfringens are alco-
tested positive for C. difficile, metroni- mended for treatment17. non-pathogenic Campylobacter species hol-resistant, but susceptible to bleach
dazole can be tried, although there are n Salmonella or persistence of clinical signs due to (1:10 to 1:20 dilution of regular house-
not many data evaluating treatment in Only systemically ill or immunocom- another unidentified cause. hold bleach) and accelerated hydrogen
dogs17. C. perfringens infections should promised dogs infected with Salmonella n Many veterinarians prescribe antibiotics peroxide. Washing hands with soap and
only be treated with antibiotics if an- spp. should be treated with antibiotics. if dogs show acute haemorrhagic diar- water should therefore be preferred over
imals are systemically ill. Ampicillin, Treatment should be based on C&ST, rhoea and are systemically ill12. However, a the use of alcohol-based hand sanitizers.

206 207
Gastroenteritis due to bacterial pathogens
Campylobacter, Salmonella, Clostridium, E.coli

Treatment recommendations
Antibiotics that can be used if bacteria have been confirmed as the cause of diar-
rhoea in systemically ill animals:
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Erythromycin 20 mg/kg/12h PO 5-21 days
Campylobacter spp.
Enrofloxacina,b 5 mg/kg/24h PO, SC 5-7 days

Amoxicillin, ampicillin 10-20 mg/kg/8h PO, IV 7-10 days


Trimethoprim 15-30 mg/kg/12-24h
Salmonella spp. 7-10 days
sulfonamidesc PO, IV
Enrofloxacina,b 5 mg/kg/24h PO, SC 5-7 days

Clostridium
Metronidazole 10-15 mg/kg/12h PO 5-10 days
perfringens

Clostridium difficile Metronidazole 10-15 mg/kg/12h PO 5-10 days


Escherichia coli
Enrofloxacina,b 5 mg/kg/24h PO, SC 8 weeks
in granulomatous colitis
a In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
b Avoid use in growing dogs of large breeds.
c Avoiduse longer than 3 weeks as risk of keratoconjunctivitis sicca (KCS) and nephrotoxicity. Schirmer tear testing
is recommended if use > 3 weeks20.

208 209
Hepatobiliary infections
Pathogen 3: Anaerobes
Bacteria involved Antibiotics that can be used
In vitro Tissue Treatment Sensitivity
and distribution
sensitivity distribution choice
1 = nil
Bacteria Prevalence Reported associations Ampicillin / Amoxicillin 4 4 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


3 = average
Clindamycin 5 5
4 = good
Escherichia coli * ++ (15 to 40 %) Aerobes + Anaerobes Metronidazole 5 5 5 = excellent
Treatment
Amoxicillin + clavulanate 4 4 choice
Enterococcus spp.** ++ (15 to 40 %)
Pradofloxacin a,c 3 5
1st line
Anaerobes a Avoid use in growing dogs of large breeds.
(Bacteroides spp., ++ (15 to 40 %) b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not
2nd line
Clostridium spp. and others) exceed 5 mg/kg.
c Pradofloxacin is a last resort choice due to its very extended spectrum of activity
* Most common Gram-negative aerobe Last resort
** Most common Gram-positive aerobe and should only be used if a narrower spectrum antibiotic cannot be used (based on
sensitivity testing results).
Excluded
for this
indication
Antibiotics that can be used
Antibiotics that can be used while awaiting C&AST results (if the use of antibiotics is
justified): Therapeutic approach
Pathogen 1: Escherichia coli
Suspicion of hepatobiliary infection
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution Empirical treatment
sensitivity distribution choice
1 = nil
Ampicillin / Amoxicillin 3 4 2 = weak
3 = average Amoxicillin + clavulanate
Amoxicillin + clavulanate 3 4
4 = good
Cefalexin / Cefadroxil 3 4 5 = excellent +
Treatment
Marbofloxacina / Enrofloxacina,b 4 5 choice Refer to a specialist
4 5
for bile sample or liver biopsy
Pradofloxacina,c
1st line Culture and sensitivity
Pathogen 2: Streptococcus spp.
2nd line
In vitro Tissue Treatment E. Coli or Streptococcus Anaerobes
Antibiotics that can be used
sensitivity distribution choice Last resort
Ampicillin, amoxicillin,
Ampicillin / Amoxicillin 4-5 4 Ampicillin, amoxicillin
Excluded clindamycin
Amoxicillin + clavulanate 4-5 4 for this
indication
a
Marbofloxacin / Enrofloxacin a,b 4 5
Amoxicillin + clavulanate, Amoxicillin + clavulanate,
marbofloxacin, enrofloxacin metronidazole

210 211
Hepatobiliary infections

Treatment recommendations Diagnostic approach


First choice antibiotic n Several situations may be associat- cholecystitis, (rare but associated with
Some of them need culture and sensitivity before use (e.g. amoxicillin or ampicillin), ed with bacterial hepatobiliary infec- Clostridium spp.) and biliary peritonitis.
as resistances are frequent (especially for E. Coli). While awaiting referral for sam- tions: septicaemia, hepatic abscesses n Bile should be collected by ultra-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


pling and culture and sensitivity, amoxicillin + clavulanate (second choice antibiotic) (rare), granulomatous hepatitis (rare), sound-guided or intraoperative chole-
can be used empirically. cholangitis and cholangio-hepatitis (in cystocentesis or liver biopsies should be
cats), cholecystitis, emphysematous taken; aerobic and anaerobic bacterial
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used

Amoxicillin 11-22 mg/kg/12h


Escherichia coli
Enterococcus spp.
Ampicillin 10 mg/kg/12h
Until clinical
improvement,
Amoxicillin 11-22 mg/kg/12h
on average
6-8 weeks
Anaerobes Ampicillin 10 mg/kg/12h

Clindamycin 5.5-11 mg/kg/12h

Second choice antibiotic


a b
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used

Amoxicillin + clavulanate 12.5-25 mg/kg/8-12h PO


Escherichia coli 2 mg/kg/24h PO
Marbofloxacina
Enterococcus spp. (dogs and cats)
Enrofloxacina,b 5 mg/kg/24h PO (dogs) Until clinical
improvement,

© Rui Lemos Ferreira


Dogs:
on average
10-15 mg/kg/12h PO,
6-8 weeks
Metronidazole SC, slow IV infusion
Anaerobes Cats:
8-10 mg/kg/12h IV, PO
c d
Amoxicillin + clavulanate 12.5-25 mg/kg /8-12h PO
Figure 1 - Suppurative cholangitis in a cat. Biliary obstruction in a cat with suppurative cholan-
a Avoid use in growing dogs of large breeds. gitis/cholecystitis. Longitudinal image of the gallbladder (a) and common bile duct (b), which are
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
both dilated and have a thickened wall. A small, moderately echogenic lesion is present in the
distal common bile duct, just proximal to the duodenal papilla (c, d). This lesion was confirmed to
be a pyogranulomatous inflammation. Ultrasound-guided cholecystocentesis was performed to
obtain a sample of bile for culture (positive for Streptococcus).

212 213
Hepatobiliary infections

culture should be performed. Results cultures8. Cultures from cats tend to


of bile culture should be interpreted yield single bacterial growth (83%) com-
together with cytology results and clin- pared to cultures from dogs, which tend
ical signs. In animals with hepatobiliary to equally yield either multiple bacterial
infection, the cytological examination species or a single isolate8. If there is a
DISEASE FACT SHEETS

DISEASE FACT SHEETS


of bile may show increased numbers risk of gallbladder leakage or rupture,
of degenerated neutrophils, mononu- cholecystocentesis should be avoided.
clear cells and in some cases a mixed Blood cultures may be useful. In human
or monomorphic bacterial population1. patients with acute cholecystitis, 30% to
n Biliary cultures are more likely to have 40% of blood cultures are positive, and
positive results overall than hepatic 50% to 95% of bile cultures are positive7.

Reasoning
n Empirical treatment with amoxicillin would need culture before use as re-
+ clavulanate can be done while waiting sistances are frequent. If sensitive, they
for the AST results. If the collection of should be the first-line treatment.
bile is not possible by the veterinarian, n The duration of antibiotherapy should
this empirical treatment can be started be adjusted according to clinical signs,
while referring. with treatments lasting several weeks
n For E. coli, amoxicillin and ampicillin often necessary.

Difficulties and particularities


n In animals with jaundice or important liver effects or with extensive hepatobil-
hepatic damage (revealed by hypoalbumi- liary activation, biotransformation or ex-
naemia, hypocholesterolaemia, hypogly- cretion should be avoided (e.g. doxycycline,
caemia, hypo-uraemia or an increase in lincomycin, erythromycin, sulfonamides,
plasma bile acids), the antibiotic dose or trimethoprim sulfonamides and chloram-
administration interval should be adjust- phenicol)7. The metronidazole dose is gen-
ed. Antibiotics associated with adverse erally halved (maximum 7.5 mg/kg/12 h).

214 215
DISEASE FACT SHEETS

216
SURGERY

217

DISEASE FACT SHEETS


Osteomyelitis
Pathogen 2: Streptococcus spp.
Bacteria involved In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Bacteria Prevalence Reported associations Amoxicillin + clavulanate 4 2 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


3 = average
Mixed infection* in 30-60% Clindamycin 4 4
Staphylococcus spp. +++ (35 to 65 %) 4 = good
Cefalexin / Cefadroxil 4 3 5 = excellent
Anaerobes in up to 60% Treatment
Streptococcus spp. ++ (15 to 40 %) a
Marbofloxacin / Enrofloxacin a,b 4 5 choice
Cefovecin 5 3
Escherichia coli ++ (15 to 40 %) 1st line
Gentamicin d 4 3
* 30 % of mixed infections associate anaerobes (Bacteroides, Fusobacterium) and aerobes (Pasteurella, Klebsiella) 2nd line
when osteomyelitis was secondary to bites 3.
Staphylococcus is more frequently isolated as the unique germ when only one germ is responsible for the infec-
tion3.
Pathogen 3: E.coli Last resort

In vitro Tissue Treatment Excluded


Antibiotics that can be used for this
sensitivity distribution choice
Antibiotics that can be used Amoxicillin + clavulanate 4 2
indication

Antibiotics that can be used if the use of antibiotics is justified: Cefalexin / Cefadroxil 4 3
Pathogen 1: Staphylococcus spp. a
Marbofloxacin / Enrofloxacin a,b 4 5

In vitro Tissue Treatment Sensitivity Cefovecin c 5 3


Antibiotics that can be used and distribution
sensitivity distribution choice Gentamicin d 3-4 3
1 = nil
Amoxicillin + clavulanate 4 2 2 = weak
3 = average a Avoiduse in growing dogs of large breeds.
Clindamycin 4 4
4 = good b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
Cefalexin / Cefadroxil 4 3 5 = excellent c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if

Treatment sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
a
Marbofloxacin / Enrofloxacin a,b 4 5 choice possible.
d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Cefovecin c
5 3
1st line www.iris-kidney.com/education/prevention.html).
Gentamicin d
4 3
2nd line

Last resort

Excluded
for this
indication

218 219
Osteomyelitis

Therapeutic approach Treatment recommendations


n Non-antibiotic treatment: remove infected implants, review unstable fixation, cu-
rettage of sequestra/abscesses.
Culture and sensitivity n Local antibiotic treatment: placement of antibiotic-impregnated implants.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


First choice antibiotic
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Empirical treatment
Implant removal if possible
while awaiting results Cefalexin 15-30 mg/kg/12h PO

Cefadroxil 10-20 mg/kg/12h PO Up to 2 weeks beyond


Staphylococcus spp.
Amoxicillin+clavulanate, Streptococcus spp.
clinical and
cefalexin, Amoxicillin + 12.5 -25 mg/kg/8-12h radiographic resolution
E.coli
clavulanate PO of the infection.
cefadroxil, clindamycin
Clindamycin 11 mg/kg/12h PO

Second choice antibiotic (with culture and sensitivity testing)


Results of Implant removal if possible Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
culture and sensitivity Placement of
De-escalate if possible, antibiotic-impregnated Marbofloxacina 2 mg/kg/24h PO
adapt if necessary implants if needed Up to 2 weeks beyond
clinical and
Enrofloxacin a,b 5 mg/kg/24h PO
radiographic resolution
of the infection.
Amoxicillin ± clavulanate, Staphylococcus spp.
Gentamicind
7 mg/kg/24h-IV
cefalexin, Streptococcus spp. Local beadse
E.coli
cefadroxil, clindamycin Up to 2 weeks beyond
8 mg/kg clinical and
Cefovecinc single dose SC radiographic resolution
(14 days) of the infection.
Enrofloxacin, marbofloxacin (1 injection per 14 days)
a Avoiduse in growing dogs of large breeds.
b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
Gentamicin, cefovecin c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
possible.
d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).
e Unsuitablefor long-term treatment (potentially nephrotoxic, systemic diffusion possible) – see www.iris-kidney.
com/guidelines/index.html

220 221
Osteomyelitis

are not a realistic option as the treatment regularly monitored (see IRIS guidelines
Diagnostic approach will take weeks to months, but if they for more information: www.iris-kidney.
n Osteomyelitis can be haematogenous, n Bacteriology should include screen- are used, the renal function should be com/guidelines/index.html).
traumatic or post-surgical, and can be ing for anaerobes that may be present
acute or chronic. The origin of infection in case of telluric infections (e.g. soiled
DISEASE FACT SHEETS

DISEASE FACT SHEETS


must be determined to eliminate the open fractures).
cause, e.g. distant infection or a foreign Difficulties and particularities
body (gunshot, sutures, implants).
n Post-surgical chronic osteomyelitis is of Paris, collagen matrix) or, more fre-
n Surgical treatment is usually manda-
often diagnosed several weeks, months quently, non absorbable (bone cement).
tory to eliminate ischemic and necrotic or even years after the operation. It is Antibiotic implants can have a systemic
tissue that harbour bacteria and protect associated with the appearance of a fis- diffusion. For implants, a follow-up of
them from antibiotics; to eliminate for- tula, local sensitivity at the level of the renal function is recommended.
eign bodies that form a biofilm, protect- implants or lameness. It may be sus- n Blood-borne (haematogenous) osteo-
ing germs from the immune system and pected during radiographic monitoring
from antibiotics; and to take samples for myelitis is rare. Radiographically, it is
of fracture healing, in the case of de- characterised by osteolytic and osteo-
culture and sensitivity testing. layed healing or implant migration. productive lesions and needs to be dif-
n Bones can heal even in the presence
n If the infection occurs after bone heal- ferentiated from bone tumours.
of infection if the biological criteria for ing, simple removal of the implant and n Young, growing animals have a spe-
bone healing are present: stability, vas- a short course of antibiotics are usually

© Hervé Brissot
cularisation of the bone and surround- cific epiphyseal vascularisation that is
sufficient to resolve the infection. potentially favourable for the sequestra-
ing soft tissue. When revising an infect-
n An acute postoperative infection, be- tion of bacteria in the capillaries under
ed fracture site, fracture stability needs
to be assessed after debridement. fore healing is complete, can be a sur- the growth plate cartilage.
Figure 1 - Chronic osteomyelitis over a pre- gical challenge: an unstable fracture
n Half of infections due to implants are
vious surgical repair of a femoral fracture. needs to be stabilised, which can be
secondary to colonisation of the surgical Despite the chronic infection and inadequate even more difficult after debridement
site by bacteria of the skin or the direct fixation, the fracture has healed but there is
of necrotic tissue in an infected context.
environment during surgery: Staphylo- still bone resorption around the infected wire.
Rigid osteosynthesis is essential and al-
coccus aureus or S. pseudintermedius. though external fixation is the method
of choice in such cases, internal fixation

© Hervé Brissot
is possible as long as implants are re-
Reasoning moved after healing.
n After surgery, effective broad-spec- be monitored (degree of lameness, pain n The use of antibiotic implants (beads

trum antibiotic treatment (e.g. cefalex- upon deep palpation, radiographic evi- or pellets) allows a high local antibi- Figure 2 - Implant of plaster of Paris im-
in, cefadroxil, amoxicillin+clavulanate) dence of bone healing). otic concentration for several days to pregnated with an antibiotic (tobramycin) in
weeks. They should not be considered a revised TTA surgery. This pellet will induce
should be provided until the result of the n Most antibiotics have good bone pene-
bone formation in the osteotomy gap and will
culture and sensitivity tests are known. tration. Tetracyclines are not appropriate as an alternative to debridement but as allow local high concentration of antibiotics.
Duration of treatment should be at least in the case of osteomyelitis as they are a complementary measure. Antibiotic
4-6 weeks, and its clinical efficacy should inactivated by calcium. Aminoglycosides implants are either absorbable (plaster

222 223
Osteomyelitis

Osteomyelitis - clinical suspicion:


Imaging/fistula/lameness
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Deep tissue aspiration

Culture and sensitivity

While awaiting
results

Empirical antibiotic therapy.


Consider implant removal if possible. Targeted antibiotic
therapy:
de-escalate if possible,
adapt if necessary

Clinical/Radiographic
improvement ?
No Yes

Revise antibiotic treatment.


Continue treatment
Re-imaging,
until radiographic healing
surgical debridement and
of the bone lesions.
re-sampling for culture & sensitivity
Consider implant
(tissue, infected implant).
removal if possible.
Revised osteosynthesis.

Figure 3 - Diagnosis, treatment and follow-up for osteomyelitis.

224 225
Septic arthritis
Pathogen 2: Streptococcus spp.
Bacteria involved In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Bacteria Prevalence Amoxicillin + clavulanate 4 2 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


3 = average
Clindamycin 4 4
Staphylococcus spp. +++ (35 to 65 %) 4 = good
Cefalexin / Cefadroxil 4 3 5 = excellent
Treatment
Streptococcus spp. ++ (15 to 40 %) a
Marbofloxacin / Enrofloxacin a,b 4 5 choice
Cefovecin c 5 3
Escherichia coli + (< 10-20 %) 1st line
Gentamicin d 4 3
2nd line

Antibiotics that can be used Pathogen 3: E.coli


Last resort
Antibiotics that can be used if the use of antibiotics is justified: In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice Excluded
Pathogen 1: Staphylococcus spp. Amoxicillin + clavulanate 4 2
for this
indication
In vitro Tissue Treatment Sensitivity Cefalexin / Cefadroxil 4 3
Antibiotics that can be used and distribution
sensitivity distribution choice a
Marbofloxacin / Enrofloxacin a,b 4 5
1 = nil
Amoxicillin + clavulanate 4 2 2 = weak 5 3
Cefovecinc
3 = average
Clindamycin 4 4
4 = good
a Avoiduse in growing dogs of large breeds.
Cefalexin / Cefadroxil 4 3 5 = excellent
b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
Treatment
a
Marbofloxacin / Enrofloxacin a,b 4 5 choice c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
Cefovecinc 5 3
1st line possible.
Gentamicin d 4 3 d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).
2nd line

Last resort

Excluded
for this
indication

226 227
Septic arthritis

Therapeutic approach Treatment recommendations


First choice antibiotic
Cytology Antibiotics that
Pathogen involved Dosage Duration of treatment
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Culture and sensitivity can be used
Staphylococcus spp.
Amoxicillin +
Streptococcus spp. 12.5-25 mg/kg/12h PO
clavulanate
E.coli
4 weeks minimum
Empirical treatment Cefalexin 15-30 mg/kg/12h PO
(2 weeks after clinical
while awaiting results resolution)
Staphylococcus spp.
Cefadroxil 10-20 mg/kg/12h PO
Streptococcus spp.
Amoxicillin+clavulanate, Clindamycin 11 mg/kg/12h PO
cefalexin,
cefadroxil, clindamycin Second choice antibiotic (with culture and sensitivity testing)
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used

Marbofloxacina 2 mg/kg/24h PO
Results of
culture and sensitivity Enrofloxacina,b 5 mg/kg/24h PO
Staphylococcus spp. 4 weeks minimum
De-escalate if possible, Streptococcus spp. 7 mg/kg/24h IV (2 weeks after clinical
adapt if necessary E.coli Gentamicin resolution)
Local beadsd
8 mg/kg
Cefovecinc single dose SC
Amoxicillin ± clavulanate, (14 days)
cefalexin, a Avoiduse in growing dogs of large breeds.
cefadroxil, clindamycin b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
possible.
Enrofloxacin, marbofloxacin d Unsuitable for long-term treatment (potentially nephrotoxic, systemic diffusion possible) – see www.iris-kidney.
com/guidelines/index.html

Gentamicin, cefovecin

228 229
Septic arthritis

Diagnostic approach Reasoning


n Arthritis can be blood-borne (haema- n First-intention antimicrobial treat-
togenous), traumatic or postsurgical, and ment (amoxicillin+clavulanate, cefalexin
can be acute or chronic. The origin of in- or clindamycin) should be prescribed for
DISEASE FACT SHEETS

DISEASE FACT SHEETS


fection must be determined to eliminate four weeks and should be continued for
the cause, e.g. distant infection or a for- at least two weeks after resolution of
eign body (gunshot, sutures, implants). the clinical signs. The treatment should
n Surgical treatment is mandatory to be re-evaluated with the sensitivity re-
eliminate foreign bodies that form a bio- sults.

© Hervé Brissot
film, protecting germs from the immune n In case of septic haematogenous ar-

© Hervé Brissot
system and antibiotics. It also allows thritis, broad-spectrum antibiotics are
taking samples for culture and sensitiv- recommended.
ity testing. n Young growing animals are predis-
n Blood-borne septic arthritis is char- Figure 2 - Arthrocentesis of the patient in posed to septic arthritis. The use of Figure 3 - Cytology of the arthrocentesis
acterised by the infection of a single Figure 1 allowed removal of frank pus. fluoroquinolones should be limited as sample (Figure 2) showed degenerative neu-
joint (as opposed to polyarthritis) in as- they can have a negative impact on the trophils and cocci.
sociation with a major local inflamma- n The final diagnosis is made using growth plate cartilage.
tory reaction (swelling, pain...). arthrocentesis, yielding abundant, tur-
bid synovial fluid. Cytology confirms a
severe inflammation with polynuclear Difficulties and particularities
neutrophils, sometimes with bacteria n In the absence of clinical improve-
(phagocytised). ment after 2 weeks, treatment should
n Culture and sensitivity testing of syn- be re-evaluated by joint lavage and
ovial samples can be a challenge as re-sampling for new culture and sen-
frequent false negatives occur. Culture sitivity testing, followed by adjustment
should include blood-based media in- of the treatment. Sampling of synovial
cubated for at least 24 hours. villi via small arthrotomy or arthroscopy
n In the absence of foreign bodies, ar- is indicated. If re-sampling is consid-
throtomy (debridement, biopsy of the ered, antibiotics should be discontinued
synovial capsule) is only required in for 24-48 hours to increase the odds of

© Hervé Brissot
collecting a relevant sample.
© Hervé Brissot

case of treatment failure. Irrigation and


drainage of the joint will help counter
the inflammation.
n In case of a traumatic lesion penetrat- Figure 4 - Articular lavage of a hock in a
Figure 1 - Severe septic arthritis of the car- ing the joint, open flushing is required to 7-month-old Gordon Setter with arthritis.
pus with marked oedema. ensure the removal of any foreign body
and necrotic tissue.

230 231
Septic arthritis

Joint effusion
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Arthrocentesis
Pus? (macroscopic-cytology)

© Hervé Brissot
Culture and sensitivity 6 7
Figures 6-7 - Border collie showing severe pain and local oedema and sensitivity of the stifle,
While awaiting 4 weeks after extra-articular stabilization of a cranial cruciate ligament rupture. Perioperative
results view: lavage and debridement of a severe joint infection. The infected prothesis was removed and
kept for culture and sensitivity.

Empirical antibiotic therapy Targeted antibiotic


Joint lavage therapy:
de-escalate if possible,
adapt if necessary

Clinical improvement ?
No Yes

Revise antibiotic treatment.


Consider re-imaging.
Continue treatment
Repeat joint lavage and
2 weeks after
surgical exploration.
resolution of the effusion
Resampling for
culture & sensitivity (tissue).

Figure 5 - Diagnosis, treatment and follow-up for septic arthritis.

232 233
Wound infections and
abscesses
Surgical debridement, abscess drainage and lavage are the first lines of Pathogen 2: Staphylococcus spp.
treatment.
Tissue Sensitivity
Antibiotics are reserved for contaminated/dirty wounds, deep lacerations Antibiotics that can be used
In vitro distribution Treatment and distribution
or systemically impaired patients (fever or severe systemic infection). sensitivity choice 1 = nil
Wound Abscess 2 = weak
Only a short course of antibiotics (4-5 days) is indicated after closure of open conta-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Amoxicillin + clavulanate 5 4 2 3 = average
minated wounds. 4 = good
Cefalexin / Cefadroxil 5 5 2 5 = excellent

Bacteria involved Marbofloxacina / Enrofloxacina,b 5 5 2 Treatment


choice
Cefovecin c 2 5 2
1st line
Bacteria Prevalence Reported associations Gentamicin d 4 4 2
2nd line
Pasteurella multocida (cats) +++ (35 to 65 %) Aerobes + anaerobes Pathogen 3: Anaerobes
(e.g. Fusobacterium in cats,
Last resort
Bacillus or Clostridium Tissue
Staphylococcus spp. (dogs) ++ (15 to 40 %) in dogs). In vitro Treatment
Antibiotics that can be used distribution Excluded
sensitivity choice
Wound Abscess for this
Enterococcus / Escherichia coli (dogs) ++ (15 to 40 %) indication
Amoxicillin + clavulanate 5 4 2
Cefalexin / Cefadroxil 5 5 2
Antibiotics that can be used Clindamycin 5 4 2

Antibiotics that can be used: only in presence of fever or systemic impairment Metronidazole 5 5 2
Cefovecin c 5 5 2
Pathogen 1: Pasteurella Pradofloxacina,e 5 5 2
Tissue Sensitivity
In vitro distribution Treatment and distribution
Antibiotics that can be used a Avoiduse in growing dogs of large breeds.
sensitivity choice 1 = nil
Wound Abscess b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
2 = weak c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
Amoxicillin 5 4 2 3 = average sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
Amoxicillin + clavulanate 5 4 2 4 = good possible.
5 = excellent d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Cefalexin / Cefadroxil 5 5 2 Treatment www.iris-kidney.com/education/prevention.html).
choice e Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
a
Marbofloxacin / Enrofloxacin a,b 5 5 2
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
Cefovecinc 2 5 2 1st line

2nd line

Last resort

Excluded
for this
indication

234 235
Wound infections and abscesses

Therapeutic approach Treatment recommendations


Abscesses: No antibiotic unless fever or severe systemic infection. n Non-antibiotic treatment: surgical debridement, abscess drainage and lavage are
Surgical debridement, abscess drainage and lavage usually suffice. the first lines of treatment. Antibiotics are reserved for contaminated/dirty wounds,
deep lacerations or systemically impaired patients.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


n Open wounds (by definition, any open wound is contaminated):
First choice antibiotic
Clean (contaminated) Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Pasteurella multocida
Amoxicillin 11-22 mg/kg/12h Clean: 4-5 days if
Direct closure (cats)
closure.
If fully granulated, Staphylococcus Amoxicillin + clavulanate 12.5-25 mg/kg/12h Dirty or deep:
open management Escherichia coli
Pasteurella until establishment
Amoxicillin+clavulanate, No need for antibiotics Cefalexin 15-30 mg/kg/12h of healthy granulated
Anaerobes
cefalexin, cefadroxil (4-5 days) tissue,
Anaerobes Clindamycin 5.5-11 mg/kg/12h usually 7-10 days.

Infected
Second choice antibiotic (with culture and sensitivity testing)
Antibiotics that
Culture and sensitivity Pathogen involved
can be used
Dosage Duration of treatment

Clean: 4-5 days if


Marbofloxacina 2 mg/kg/24h closure.
Empirical treatment while Amoxicillin+clavulanate, Pasteurella Dirty or deep:
Staphylococcus 5 mg/kg/24h
awaiting results cefalexin, cefadroxil until establishment
Pseudomonas (Up to 11-20 mg/kg/12 h of healthy granulated
Enrofloxacin a,b
for resistant tissue,
Pseudomonas) usually 7-10 days.
Results of culture and sensitivity
For footnotes, see p.235.
De-escalate if possible, adapt if necessary

Amoxicillin ± clavulanate, cefalexin,


cefadroxil, clindamycin, metronidazole Diagnostic approach
n Open wounds can be classified as clean n In general, the flora within the wound
(surgically created in sterile setting), is likely to be restricted to opportunistic
Enrofloxacin, marbofloxacin clean contaminated (clean wound with environmental germs without extreme
surgical opening of an internal tract or pathogenicity. Infection is the result of
older than 6 hours), contaminated (as the interaction between tissue, patient
Cefovecin, pradofloxacin above with tract spillage or clean older than and germs (pathogenicity and quanti-
12 hours) and dirty (pus, necrotic tissue). ty). Healthy tissues in a healthy patient

236 237
Wound infections and abscesses

will not develop infection and will there- n Bacterial contamination can also n Antibiotics are not indicated unless
fore not need extensive antibiosis. Sick be managed with the use of antiseptic the wound is infected, contains devi-
or weak patients will be more prone to solutions or specific dressings. Topical talised tissues and/or the patient is in
develop infection even with non-aggres- antibiotic therapy is not routinely rec- poor condition. Ideally, culture and sen-
sive bacteria. ommended. Local exudation at the level sitivity testing is performed prior to in-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


n Antibiotics are not an alternative to of the wound is likely to dilute the an- itiating antibiotic therapy. The bacteria

© Hervé Brissot
physical cleaning and debridement. De- tibiotics locally. This will lead to a con- most likely to be found in open wounds
bridement of healthy granulation tissue centration lower than the MIC, creating are Staphylococcus spp., Streptococcus
around a wound is not always indicated favourable conditions for the selection spp. and E.coli (from the patient’s skin/
as it helps seal the wound content away of resistant bacteria. hair-coat), Pasteurella spp. and anaer-
obes in case of bite wounds. Figure 4 - Partial closure of the wound with
from the rest of the body. an axial pattern flap. A small area has been
n ß-lactams (amoxicillin±clavulanate, left open to allow drainage and prevent ten-
cefalexin or cefadroxil) can be used em- sion. Antibiotics can be discontinued after 3
pirically. If anaerobes are a concern (e.g. days as only healthy tissue remains.
deep wounds with soil contamination or
secondary to bites) trimethoprim sulfo- n Fluoroquinolones are not indicated

© Hervé Brissot
namides, possibly associated with met- for first-intention use unless sensitivity
ronidazole or clindamycin, are indicat- testing shows this is the only effective
ed. antibiotic.
1 2 3
Figures 1, 2, 3 - Treatment of an open wound. This dog developed a deep abscess and skin necrosis
in the flank following bite wounds.
Figure 1 - Aspect of the wound upon admission, with pus and clear necrotic tissue. Difficulties and particularities
Figure 2 - Initial treatment involving surgical debridement and instauration of first-intention antibiotic
therapy (amoxicillin+clavulanate). The wound was dressed and superficially debrided on a n Regardless of size, open wounds surgery.
daily basis. should be treated with antibiotics until - However, long-term use of antibiotics
Figure 3 - Aspect of the wound after 7 days. Necrotic tissue or evidence of infection are no longer healthy granulation tissue is observed
visible, the wound is almost completely covered by healthy (pink) granulation tissue, making for the treatment of open wounds can
surgical reconstruction possible.
to adequately control bacterial growth. lead to the selection of multiresistant
- Chronic open wounds may harbour Staphylococcus or Pseudomonas or
low-grade multiresistant bacteria that even to yeast colonisation. If this hap-
Reasoning may prevent successful healing after pens, antibiotic treatment should be
closure/reconstructive surgery. In these discontinued and be replaced by specific
n Abscesses should be treated by lanc- The systematic use of antibiotics in pa-
cases, tissue samples should be taken antibacterial dressings (honey or silver
ing, flushing and draining. Antibiotics tients with a cutaneous/subcutaneous
of the granulation tissue in order to have based) or even biological debridement
may be considered in patients with sys- abscess without systemic signs is ques-
a sensitivity test result at the time of the (maggots) to achieve healing.
temic signs. Sampling for culture and tionable. Surgical debridement, abscess
sensitivity testing should be reconsid- drainage and lavage usually suffice. This
ered if the treatment fails or if another does not apply for cases with extensive
abscess appears close to the first one or septic cellulitis.
soon afterwards.

238 239
Wound infections and abscesses

Open wound Abscess


DISEASE FACT SHEETS

DISEASE FACT SHEETS


Possibly associated Diffuse purulent
Fully Well organized abscessation
Acute-clean Dirty / Infected with foreign body
granulated-clean
Consider
biopsy Incision, lavage, Surgical exploration, Incision, lavage,
for C&AST Drainage or drainage. ideally guided by drainage.
surgical pre-operative imaging. If recurrent
Patient
debridement systemically Tissue sampling or patient
affected*? for C&AST. systemically
Consider Yes No affected*:
biopsy tissue sampling
for C&AST for C&AST.

Acute-clean?
Yes No
Sample for C&AST Local wound
Empirical antibiotherapy
Empirical antibiotherapy care
while awaiting
while awaiting until
C&AST results.
C&AST results. healing.

Open
Open management Direct closure wound management
until (+/- with drain). until granulation. Not healed/recurred
epithelialisation. Short course C&AST: after 7-10 days?
No need (4-5 days) 1st line antibiotics,
for antibiotics. 1st line antibiotics. adjust according
to C&AST results. Repeat C&AST.
Consider possible foreign body, pilonidal cyst or fistula
of the gastro-intestinal, urinary or respiratory tracts.
Figure 5 - Diagnosis, treatment and follow-up for an open wound. *
Signs of sepsis: marked hyperthermia, lethargy, leucocytosis (with/without left shift),
possible alteration of glucose levels
Figure 6 - Diagnosis, treatment and follow-up for abscesses.

240 241
Septic peritonitis
Pathogen 2: Gram-positive (Enterococcus, Staphylococcus)
Bacteria involved In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Bacteria Prevalence Amoxicillin / Ampicillin 4 3 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


3 = average
Clindamycin 4 5
Escherichia coli +++ (35 to 65 %) 4 = good
Amoxicillin + clavulanate 4 3 5 = excellent
Treatment
Enterococcus spp. ++ (15 to 40 %) Cefalexin / Cefadroxil / choice
4 3
Cefazolin / Cefalothin
Pasteurella spp. + (< 10-20 %) Marbofloxacina / Enrofloxacina,b 4 5 1st line

Cefovecinc 4 3 2nd line


Staphylococcus + (< 10-20 %)
Pathogen 3: Obligate anaerobes (e.g. Clostridium, Bacteroides, Last resort
Fusobacterium)
Antibiotics that can be used In vitro Tissue Treatment
Excluded
for this
Antibiotics that can be used indication
sensitivity distribution choice
The first route for patients with septic peritonitis is IV, which may guide Amoxicillin / Ampicillin 4 3
the choice of antibiotic. Clindamycin 4-5 5
Metronidazole 5 3
Pathogen 1: Gram-negative (E. coli, Pasteurella, Klebsiella)
Amoxicillin + clavulanate 4 3
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution Pradofloxacina,e 4-5 5
sensitivity distribution choice
1 = nil
Amoxicillin + clavulanate 3-4 3 2 = weak a Avoiduse in growing dogs of large breeds.
3 = average b In
Marbofloxacina / Enrofloxacina,b 4 5 cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
4 = good c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
Cefalexin / Cefadroxil / 5 = excellent sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
3 3
Cefazolin / Cefalothin Treatment possible.
choice d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Cefovecinc 5 3
www.iris-kidney.com/education/prevention.html).
Aminoglycosides d 5 3 1st line e Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
2nd line

Last resort

Excluded
for this
indication

242 243
Septic peritonitis

Therapeutic approach Treatment recommendations


n Abdominal exploration, debridement, control and resolution of the source of contami-
nation, abdominal drainage, feeding strategy to control and reverse hypoproteinaemia.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Culture and sensitivity n Sampling for culture and sensitivity testing is highly recommended before start-
ing antibiotic therapy. It should be done with the initial sample collected for the
diagnostic paracentesis or from tissue collected during exploratory laparotomy.
Initial clinical management will implicate the use of IV antibiotics. The use of amino-
Emergency empirical Amoxicillin ± clavulanate, glycosides should be carefully evaluated as the general condition of the patient might
treatment (IV) cefalexin, cefadroxil, make these antibiotics unsuitable due to their inherent toxicity.
while awaiting results cefazoline, cefalothin
± metrodinazole First choice antibiotic
Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Enrofloxacin, marbofloxacin
Obligate anaerobes Metronidazole 10-15 mg/kg/12h
± metronidazole
Obligate anaerobes Amoxicillin 20-25 mg/kg/8h
Results of culture 2 weeks
Gram-positive Clindamycin 5.5-11 mg/kg/12h
and sensitivity
De-escalate if possible, Gram-negative Amoxicillin + clavulanate 12.5-25 mg/kg/8 to 12h
adapt if necessary
Second choice antibiotic
Antibiotics that
Amoxicillin, ampicillin, Pathogen involved
can be used
Dosage Duration of treatment
clindamycin, metronidazole
Amoxicillin + clavulanate 12.5-25 mg/kg/8 to 12h
Mixed population
of Gram-negative Amoxicillin 20-25 mg/kg/12h
4 weeks minimum
and Gram-positive
Amoxicillin+clavulanate, aerobes
Cefalexin 15-30 mg/kg/12h (2 weeks after clinical
cefadroxil, cefazoline, resolution)
and facultative Marbofloxacina 2 mg/kg/24h
cefalothin, enrofloxacin, anaerobes
marbofloxacin Enrofloxacina,b 5 mg/kg/24h

a Avoid use in growing dogs of large breeds.


b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.

Cefovecin, aminoglycosides,
pradofloxacin

244 245
Septic peritonitis

n Septic peritonitis requires surgical and infection can lead to hypoproteinae-


Diagnostic approach intervention to debride necrotic tissue, mia, sepsis and ultimately multi-organ
n Septic peritonitis is defined by an in- related to rupture of the gastro-intestinal evacuate infected fluid and treat the or- failure.
fection of the peritoneal cavity. Primary tract. This may be due to a trauma (e.g. igin of the infection. Septic peritonitis is n The prognosis is guarded with an over-
peritonitis due to haematogenous em- road traffic accident, bite or gunshot
DISEASE FACT SHEETS

DISEASE FACT SHEETS


also a medical challenge as inflammation all survival rate of 50%.
bolisation of bacteria is a rare condition wound, foreign body), failure of a sur-
that is poorly documented in veterinary gical procedure or to tumour erosion.
Septic peritonitis can also be related to
medicine.
the rupture of hepatic or pancreatic ab- Reasoning
n Secondary peritonitis is a much more scesses, or of the urogenital tract (e.g. n Broad-spectrum antibiotics are rec-
frequent condition. 80% of cases are pyometra or prostatic abscess). ommended until results of the culture
and sensitivity testing are available. IV
bactericidal antibiotics are necessary
for the management of this severe infec-
tion, preferably using an association of
ß-lactam penicillins or first-generation
cephalosporins, aminoglycosides and
possibly metronidazole. Due to the poor
state of animals presented with abdom-
inal sepsis, aminoglycosides are often
judged unsafe due to their nephrotoxic-

© Hervé Brissot
ity. In these cases, fluoroquinolones are
preferred until the results of sensitivity
1 2
testing are known. Peritonitis is usu-
ally diagnosed as an acute infection in
systemically unstable patients that will Figure 5 - Swabbing is part of the treatment
often require hospitalisation for 1 to 2 for especially severe peritonitis requiring
weeks. Usually, treatment is started by long term medication e.g. in this biliary peri-
the IV route for several days until there tonitis.
is evidence of efficacy, then followed by
oral treatment. Gram-positive strains such as Staphy-
n Multiple bacteria are frequently in- lococcus or Streptococcus can also be
© Hervé Brissot

volved with abdominal sepsis, especially observed. E. coli should be suspected


in dogs. Typically, intestinal rupture will in case of urogenital or biliary rupture.
3 4 be associated with Gram-negative strains In cats, Enterococcus is frequently ob-
(E. coli, Klebsiella and Bacteroides), but served in urinary tract rupture.
Figures 1, 2, 3, 4 - Frequent causes of peritonitis including forgotten foreign bodies during
abdominal procedures like a surgical sponge (Fig. 1), defective/leaking intestinal anastomosis
(Fig. 2), intestinal perforation by foreign material (Fig. 3) or ruptured prostatic abscess (Fig. 4).

246 247
Septic peritonitis

Difficulties and particularities


Abdominal effusion
n Hypoproteinaemia, presence of in-
fected foreign material or necrotic tis-
sue and effusion all need to be correct-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


ed to allow the antibiotics to be effective. Paracentesis
Bacteria inside necrotic tissue or the
effusion are protected from the immune
system and out of reach of the antibi- Pus?
otics. Aggressive surgical debridement Macroscopic, cytology, peritoneal/
and effective drainage is paramount for
abdominal glucose ratio
the management of peritonitis.
While awaiting

© Hervé Brissot
n Antibiosis is no substitute for surgery
but should be used in combination with Figure 6 - Abundant irrigation and thorough results Sampling (FNA, Biopsy):
aspiration are the main component of peri- Culture & AST
this treatment. tonitis treatment and should be started as
soon as the peritoneal cavity is open.
Empirical antibiotic therapy.
Intensive care,
stabilisation prior to surgery.
Targeted antibiotic
therapy:
Surgical exploration. de-escalate if possible,
Correction of the cause adapt if necessary.
± drainage.
Tissue sampling for
7 8 culture & sensitivity.

Figures 7, 8, 9 - Abdominal drainage achieved


via an open abdominal wound which required
frequent dressing changes under aseptic condi- Clinical Improvement?
tions and eventually surgical closure (2 to 4 days
after the initial surgery) or the use of closed No Yes
drainage system with Jackson-Pratt’s drains
and suction grenades. For these, daily cytology
© Hervé Brissot

of the effusion collected from the drain (not from


the grenade) is recommended. Daily volume of
Revise antibiotic treatment Continue treatment
fluid effusion and cytology allow assessment of Consider re-imaging / for 2 weeks after
the progression of the inflammatory process.
9
surgical exploration resolution of the effusion
Figure 10 - Diagnosis, treatment and follow-up for septic peritonitis.

248 249
Post-operative infections

Bacteria involved Antibiotics that can be used


n A sample should be taken for culture and sensitivity testing before initiating treatment.
Bacteria Prevalence Reported associations Response to treatment should be monitored and if no improvement is observed after
24-48h (in case of acute and potentially life-threatening infection) to 5 days (chronic
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Staphylococcus pseudintermedius +++++ (> 75 %) infection), treatment should be revised and surgical re-sampling is required.
Meticillin-resistant Orthopaedic surgery, Pathogen 1: Staphylococcus pseudintermedius
++ (15 to 40 %)
S. pseudintermedius (MRSP) wound infections
In vitro Tissue Treatment Sensitivity
Meticillin-resistant Antibiotics that can be used and distribution
+ (< 10-20 %) sensitivity distribution choice
S. aureus (MRSA) 1 = nil
Amoxicillin + clavulanate 4 3 2 = weak
Escherichia coli ++ (15 to 40 %) 3 = average
Clindamycin 4 5
4 = good
Extended spectrum ß-lactamase Wound infections, gastro-intestinal tract, Cefalexin / Cefadroxil 4 3 5 = excellent
+ (< 10-20 %)
(ESBL) and/or AmpC producing E. coli abdominal surgery, perineal surgery Treatment
Marbofloxacina / Enrofloxacina,b 4 5 choice
Enterococcus + (< 10-20 %) Cefovecin c 4 3
1st line
Oral cavity, gastrointestinal tract, Aminoglycosidesd 5 3
Anaerobes + (< 10-20 %)
anal sacs 2nd line
Wound infections, Pathogen 2: Gram-negative
Pseudomonas aeruginosa + (< 10-20 %) Last resort
ear surgery In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice
Excluded
Amoxicillin + clavulanate 4 3 for this
indication
Marbofloxacina / Enrofloxacina,b 4 5
Cefalexin / Cefadroxil 3 3
Cefovecin c 5 3
Aminoglycosidesd 5 3

a Avoiduse in growing dogs of large breeds.


b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
© Hervé Brissot

sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
possible.
d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.htlm).

Figure 1 - Post-operative view. This boxer underwent an exploratory laparotomy. After the pro-
cedure, the wound was cleaned and a non-stick adhesive dressing has been placed immediately.
On the side of the thorax, a mass has been removed where it may be challenging to keep the
dressing in place. A non-adhesive foam dressing was sutured in place to protect the wound and
if necessary absorb any secretion.

250 251
Post-operative infections

Therapeutic approach Treatment recommendations


n The antibiotic should be available in an IV formulation for acute and potentially
life-threatening infection (see below). Amoxicillin+clavulanate and pradofloxacin
Culture and sensitivity have better anti-anaerobic activity than other ß-lactams and fluoroquinolones, but
DISEASE FACT SHEETS

DISEASE FACT SHEETS


metronidazole can be considered where there is specific concern over anaerobic
contamination.
First choice antibiotic
Empirical treatment Amoxicillin+clavulanate,
Antibiotics that
while awaiting results cefalexin, clindamycin Pathogen involved
can be used
Dosage Duration of treatment

Amoxicillin + clavulanate 12.5-25 mg/kg/12h

Gram-positive
Cefalexin 15-30 mg/kg/12h
(Staphylococcus) Until evidence
of healing
Results of culture and sensitivity Clindamycin 5.5-11 mg/kg/12h
De-escalate if possible, adapt if necessary
Gram-negative Amoxicillin + clavulanate 12.5-25 mg/kg/12h

Second choice antibiotic (after culture & sensitivity testing)


Staphylococcus Gram-negative Antibiotics that
Pathogen involved Dosage Duration of treatment
can be used
Amoxicillin+clavulanate,
Amoxicillin+clavulanate Marbofloxacina 2 mg/kg/24h
cefalexin, clindamycin
Enrofloxacina,b 5 mg/kg/24h
Gram-positive
Cefalexin, clindamycin, (Staphylococcus) Until evidence
Enrofloxacin, marbofloxacin Cefovecinc 8 mg/kg/14j-SC
or of healing
enrofloxacin, marbofloxacin Gram-negative
Gentamicind 8 mg/kg/24h

Amikacind 10-15 mg/kg/24h


Cefovecin, aminoglycosides Cefovecin, aminoglycosides
a Avoiduse in growing dogs of large breeds.
b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is not
possible.
d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).

252 253
Post-operative infections

Diagnostic approach Reasoning


n Infection of the surgical site may jeop- n Prevention of post-operative sepsis is n A classic mnemonic to remember the than of the germs responsible.
ardize the final results and be associated paramount. This is achieved by: usual causes of postoperative fever are n Initial empirical antibiosis is based on
with minor (superficial wound breakdown) • strict control of the surgical environment; the 5 W’s: Wind (e.g. pneumonia, ate-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


the surgical site and its likely contam-
to potentially fatal complications (bacter- • surgical technique: atraumatic, precise lectasis, pleural space), Water (urinary
ination: Staphylococcus spp. in case of
aemia, sepsis). dissection, precise haemostasis; tract), Wound, Walkings (or “Weins “ for
clean surgery (ß-lactams: amoxicillin,
n Diagnosis of a postoperative infection • strict post-operative hygiene; postoperative thrombosis – rare in vet-
amoxicillin+clavulanate or first-gener-
is based on type of surgery and its risk of erinary medicine) and Weird drugs or
• antibiotic prophylaxis if indicated (see ation cephalosporins) or based on the
infection (clean/clean-contaminated/con- “What did we do” for reactions to medi-
recommendation R.26 p.408). most likely contaminant for contaminat-
taminated/infected) as well as on clinical cations or line access.
n In uncomplicated healing, the surgical ed surgery (e.g. Gram-negative Entero-
and laboratory findings. n If infection is suspected, samples
wound is sealed by fibrin and oedema bacteriaceae in case of GI tract surgery).
n Postoperative inflammation (fever, lo- should be collected in a sterile manner
within 24-48 hours. During this period, prior to treatment, either by reopening n Postoperative infection can be classi-
cal redness and sensitivity) is a normal the wound should be dressed for protec- the surgical site or by percutaneous fine fied as acute, sub-acute and chronic.
response of the organism to surgical in- tion from colonisation by commensal flora
sult. However, if prolonged (more than 48 needle aspiration and submitted for cul- n Chronic infections are usually associ-
(patient, environment). Special attention ture and sensitivity.
hours or starting 48 hours after surgery) should be given to prevent contact with ated with implants (usually orthopaedic
or associated with local discharge, then hospital surfaces (e.g. X-Ray or examina- n Samples of pus or a draining tract of implants but also prosthetic sutures,
infection is suspected. tion tables, kennels). The seal should also open wounds are unreliable as they are meshes). Common clinical signs include
n Evidence of neutrophilia with left shift be protected from the patient – use an likely to show no growth at all or growth a discharging fistula with or without as-
is another element arousing suspicion of Elizabethan collar or additional dressing if of an opportunist contaminant rather sociated clinical signs (pain, lameness).
active infection. necessary.
Difficulties and particularities
n Antibiotics only have a very limited long-term use of antibiotics will favour
role in the management, as infected the selection of resistant strains. Treat-
implants will be covered by a biofilm ment requires removal of the implant,
protecting the bacteria from the im- which is cultured to identify the germs
mune system and from antibiotics. Al- involved, possibly followed by a short
© Hervé Brissot

though they may limit bacterial growth, course of targeted antibiotics.

2 3
Figures 2, 3 - Close-up view of a surgical wound closed with a continuous suture.
Figure 2 - The wound at the end of the procedure. Despite good apposition, there is a slight tension,
allowing some gaps to be seen.
Figure 3 - However, 24 hours later, the wound is fully sealed by the fibrin adhesion and local normal
postoperative oedema.

254 255
Post-operative infections

Sampling (FNA*, biopsy) for C&AST


Empirical treatment
while awaiting results
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Targeted antibiotic
therapy:
de-escalate if possible,
adapt if necessary

Clinical improvement?
Yes No

Continue treatment Consider


until evidence of healing surgical exploration
(with possibly and sampling for C&AST
implant removal)

*FNA: fine needle aspiration.

Figure 4 - Diagnosis, treatment and follow-up for post-operative infections.

256 257
Prevention of surgical complications
(including peritonitis and abscesses)
• Perioperative or postoperative antibiotic therapy is not justified. Antibiotics that can be used
• Exceptions: surgery > 90 minutes, orthopaedic procedures involving Antibiotics that can be used if the use of antibiotics is justified:
implants and/or contaminated sites.
Pathogen 1: Staphylococcus pseudintermedius
DISEASE FACT SHEETS

DISEASE FACT SHEETS


In vitro Tissue Treatment Sensitivity
Bacteria involved Antibiotics that can be used
sensitivity distribution choice and distribution
1 = nil
Amoxicillin + clavulanate 4 3 2 = weak
Bacteria Prevalence Reported associations Clindamycin 4 5
3 = average
4 = good
Cefalexin / Cefadroxil 4 3 5 = excellent
Staphylococcus pseudintermedius +++++ (> 75 %)
Treatment
Marbofloxacina / Enrofloxacina,b 4 5 choice
Meticillin-resistant Orthopaedic surgery,
++ (15 to 40 %) Cefovecin c 4 3
S. pseudintermedius (MRSP) wound infections 1st line
Meticillin-resistant Aminoglycosidesd 5 3
+ (< 10-20 %) 2nd line
S. aureus (MRSA)
Pathogen 2: E. coli and Klebsiella
Escherichia coli ++ (15 to 40 %) Last resort
In vitro Tissue Treatment
Antibiotics that can be used
Extended spectrum ß-lactamase Wound infections, gastro-intestinal tract, sensitivity distribution choice
+ (< 10-20 %) Excluded
(ESBL) and/or AmpC producing E. coli abdominal surgery, perineal surgery Amoxicillin / Ampicillin 4 4 for this
indication
Enterococcus + (< 10-20 %) Amoxicillin + clavulanate 4 4
Cefalexin / Cefadroxil 3 3
Oral cavity, gastrointestinal tract,
Anaerobes + (< 10-20 %) a
Marbofloxacin / Enrofloxacin a,b 4 4
anal sacs
Wound infections, Cefovecinc 5 5
Pseudomonas aeruginosa + (< 10-20 %)
ear surgery d 5 5
Aminoglycosides

Pathogen 3: Pseudomonas
In vitro Tissue Treatment
Antibiotics that can be used
sensitivity distribution choice
Marbofloxacina / Enrofloxacina,b 4 5
Aminoglycosides d 4 3
Ceftazidime 4 3
© Olivier Gauthier

a Avoiduse in growing dogs of large breeds.


b Incats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Cefovecin is a third generation cephalosporin and therefore a last resort antibiotic. It should only be used if
sensitivity testing indicates that other antibiotics would be ineffective or if oral administration of medication is
not possible.
d Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
Keep surgery time to a minimum – the risk of infection doubles every hour. www.iris-kidney.com/education/prevention.html).

258 259
Prevention of surgical complications
(including peritonitis and abscesses)

Pathogen 4: Enterococcus
Therapeutic approach
In vitro Tissue Treatment Sensitivity
Antibiotics that can be used and distribution
sensitivity distribution choice
1 = nil
Amoxicillin / Ampicillin 4 3 2 = weak
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Amoxicillin + clavulanate 4 3 3 = average Pre-surgery considerations
4 = good
a
Marbofloxacin / Enrofloxacin a,b 4 5 5 = excellent
Treatment
choice
Pathogen 5: Anaerobes
- Clean surgery
1st line
In vitro Tissue Treatment > 90 min
Antibiotics that can be used Clean surgery Clean surgery
sensitivity distribution choice - Clean- Contaminated-
2nd line <60 minutes 60-90 min
Amoxicillin / Ampicillin 4 3 contaminated dirty
without without
surgery surgery
Amoxicillin + clavulanate 4 3 Last resort implants implants
- Clean surgery
Metronidazole 4 3 with implants
Excluded
Pradofloxacina,e 4 5 for this
indication
a Avoid use in growing dogs of large breeds.
b In cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
e Pradofloxacin is a last resort choice due to its very extended spectrum of activity and should only be used if a Perioperative - Perioperative
narrower spectrum antibiotic cannot be used (based on sensitivity testing results).
antibiotics antibiotics
Peri and
may be indicated
Antibiotics postoperative
indicated - Conflicting
contraindicated antibiotics
considering the evidence for
indicated
risk factors postoperative
in each case antibiotics

Other recommendations
n Non-antibiotic treatment: high stand- • Perioperative antibiotics may be indi-
ards of patient preparation, tissue han- cated in:
dling and surgical technique. - Clean 60-90min surgery involving im-
n Perioperative antibiotic treatment: plants or risk of contamination,
• Antibiotic treatment is not a substitute - Clean surgery >90min,
for good surgical technique and patient - Contaminated surgery.
care. • Perioperative antibiotics reduce bac-
• Antibiotic treatment is definitely terial contamination and the risk of post-
Antibiotic treatment is contraindicated in clean surgery of less
contraindicated in clean surgery of operative infection (see flow diagram).
than 60 minutes without implants.
<60 minutes without implants.

260 261
Prevention of surgical complications
(including peritonitis and abscesses)

- Initiate IV treatment 30-60 minutes paedic surgery. operative infection with these bacteria. n Routine use of antibiotics eliminates
before surgery starts. • Antibiotic impregnated solutions, n Veterinary premises and personal are susceptible commensal bacteria, facili-
- Repeat every 60-90 minutes during beads, gels and foams may be indicat- risk factors for colonisation and infec- tating colonisation with antibiotic resist-
surgery according to drug pharma- ed if there is a high risk of contamina- tion with MRSP and MRSA. ant bacteria.
cokinetics (concentration-dependent tion with antibiotic-resistant bacteria in
DISEASE FACT SHEETS

DISEASE FACT SHEETS


antibiotics only need to be administered
once).
appropriate sites – the choice should
be based on prior culture and antibiotic
Difficulties and particularities
• Post-operative antibiotics are indi- susceptibility tests. n Staphylococci, Pseudomonas and other wherever possible.
cated where there is pre-existing con- • Clinicians should adapt their approach bacteria can form biofilms within 1-2 n Use smooth titanium implants where
tamination and/or infection. There is if the factors affecting the patient change hours of surgery. possible, and avoid damage during the
conflicting evidence whether post-op- during the surgical procedure (e.g. pro- n Biofilms facilitate adherence to im- procedure.
erative antibiotic treatment reduces longed anaesthesia, hypoxia, contami- plants, sutures, wound surfaces and n Antimicrobial-impregnated implants
surgical site infections in clean ortho- nation etc.). the skin, and protect bacteria against may reduce contamination and biofilm
antibiotics and phagocytic cells. formation, but controlled studies are re-
General approach n Use appropriate sutures, and consider quired.
absorbable and non-braided products
n High standards of patient and surgical n If possible, delay surgery until con-
site preparation (see box 1). current problems have been managed
n Good tissue handling and surgical (skin infections, skin inflammation, hy-
technique (see box 2). pothyroidism, hyperadrenocorticism, di- Box 1. Patient and surgical site preparation
n Sterile theatre environment (see box 3). abetes mellitus, obesity etc.).
• Clean gross soiling if necessary, but otherwise avoid pre-operative bathing (this
n High standards of post-operative pa- n If possible, avoid concurrent use of
can increase bacterial contamination).
tient care (see box 4). potentially immunosuppressive treat-
ment (e.g. glucocorticoids, ciclosporin, • Protect open wounds with water-soluble jelly during clipping.
n Perioperative antibiotic treatment if jus-
oclacitinib and cytotoxic drugs). • Clip an appropriate area immediately prior to surgery – avoid traumatising the
tified (see flow diagram on previous page).
skin as this increases the risk of contamination and infection.
• Gently vacuum up clipped hair.
Reasoning • Use drapes, gloves or bandages to protect contaminated areas (e.g. feet).
n Surgical interventions involve inci- n Most infections involve commensal
• Prepare the surgical site in two stages, working from the incision site to the
sions through the skin or other barriers, bacteria - most commonly S. pseudin- periphery:
tissue disruption, hypoxia and/or the termedius from the skin and mucosal
use of implants that all predispose to - Outside theatre - clean the surgical site with 50:50 warm water/4% chlorhexidine.
surfaces but also organisms from the
contamination and infection. oral cavity, gastro-intestinal tract or - In theatre - as above followed by an alcoholic solution with chlorhexidine or
Concurrent medical conditions may lower urogenital tract. Environmental bac- iodine using sterile gloves and swabs.
immunity and delay wound healing. teria are less common but can be ac- - Avoid over-vigorous rubbing and skin trauma.
n Post-operative inflammation and pain quired from contaminated environ- - Lavage contaminated sites and open wounds.
may further compromise immunity and ments or equipment. Animals colonised • Apply sterile drapes - consider waterproof adhesive drapes in high-risk procedures.
wound healing through loss of appetite with MRSP or other antibiotic-resistant
and self-trauma. bacteria are at greater risk of post-

262 263
Prevention of surgical complications
(including peritonitis and abscesses)

Box 2. Good tissue handling and surgical technique Box 4. High standards of post-operative patient care
• Keep surgery time to a minimum – the risk of infection doubles every hour. • Maintain oxygenation, blood pressure and tissue perfusion to avoid hypoxia - this
• Avoid tissue damage and necrosis. increases the risk of infection.
DISEASE FACT SHEETS

DISEASE FACT SHEETS


• Effective haemostasis avoids excessive clots and preserves the blood supply. • Maintain core and peripheral body temperature - hypothermia increases the risk
of infection.
• Good tissue apposition to eliminate dead space and avoid tension.
• Use analgesia and supportive care to avoid pain, and maintain nutrition and
• Lavage clots, debris and contamination.
hydration.
• Only use drains if necessary - consider closed sterile drains, use for the minimum
• Follow high standards of hygiene when handling patients and wounds.
time needed and prevent self-trauma.
• Prevent self-trauma but make sure that collars do not interfere with feeding or
become contaminated.
• Minimise hospitalisation and discharge patients as soon as they are clinically fit.

Box 3. Sterile theatre environment


• Hand hygiene – chlorhexidine (preferred due to persistent activity on the skin) or
iodine detergent washes followed by alcohol gels. Avoid over-vigorous scrubbing,
as this results in increased colonisation and shedding of bacteria. Alcohol and
disinfectant gels may be sufficient for subsequent hand disinfection if they are
visibly clean.
• Closed gloving.
• Change gloves if punctured.
• Clean theatre-specific scrubs, footwear, hat and gloves.
• Single-use, water-resistant sterile surgical gowns.
• Sterile equipment for each patient.
• Effective cleaning and disinfection protocols for the theatre suites and non-sterile
equipment.

Routine use of antibiotics eliminates susceptible commensal bacteria, facilitating colonisation


with antibiotic resistant bacteria.

264 265
Prevention of surgical complications
(including peritonitis and abscesses)

Recommendations of use
n Ideally, the antibiotic should be available in an IV formulation for perioperative use
(see below). Amoxicillin+clavulanate and pradofloxacin have better anti-anaerobic
activity than other ß-lactams and fluoroquinolones but metronidazole can be consi-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


dered where there is specific concern over anaerobic contamination.
n Please see recommendation R.19 p.366 for more information about MRSA/MRSP,
ESBL/AmpC producing E. coli and Klebsiella, and multi-drug resistant Pseudomo-
nas.

Pathogen involved Antibiotics that can be used Dosage

Amoxicillin+clavulanate 12.5-25 mg/kg


Clindamycin 5.5-11 mg/kg
Staphylococcus spp. Cefalexin 15-30 mg/kg
Marbofloxacina 2 mg/kg
Enrofloxacin a,b
5 mg/kg
Amoxicillin / Ampicillin 10-15 mg/kg
Amoxicillin+clavulanate 12.5-25 mg/kg
Escherichia coli
Cefalexin 15-30 mg/kg
Klebsiella spp.
Marbofloxacina 2 mg/kg
Enrofloxacin a,b
5 mg/kg
Marbofloxacina 2-5 mg/kg
Pseudomonas Enrofloxacinb 5 mg/kg
Gentamicinc 5-10 mg/kg
Amoxicillin / Ampicillin 10-15 mg/kg
Enterococcus
Amoxicillin+clavulanate 12.5-25 mg/kg
Amoxicillin / Ampicillin 11-15 mg/kg
Anaerobes Amoxicillin+clavulanate 12.5-25 mg/kg
Metronidazole 10-15 mg/kg
a Avoid
use in growing dogs of large breeds.
b In
cats, use of enrofloxacin has been associated with a risk of retinal toxicity. Do not exceed 5 mg/kg.
c Aminoglycosides are potentially ototoxic and nephrotoxic; do not use in patients with renal dysfunction (see
www.iris-kidney.com/education/prevention.html).

266 267
DISEASE FACT SHEETS

268
Dentistry

269

DISEASE FACT SHEETS


Periodontal disease

Bacteria involved Diagnostic approach


n The periodontium consists of the gin-
Bacteria Prevalence Reported associations giva, periodontal ligament, cement and
alveolar bone. First signs of periodon-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


Diseased periodontium will harbour
Actinomyces spp. ++ (15 to 40 %) tal disease include gingivitis which may
Gram-positive and obligate anaerobes
lead to periodontitis and ultimately to
Peptostreptococcus spp. ++ (15 to 40 %) Multiple strain of anaerobes tooth loss.
Normal flora is a mix of Gram-negative n The oral cavity is a naturally contam-
Porphyromonas spp. ++ (15 to 40 %)
and anaerobic germs inated area with mainly anaerobic and
Gram-negative bacteria. The perio-
Antibiotics that can be used dontium is always covered with dental
plaque, which is a biofilm harbouring
Antibiotic therapy is not indicated in periodontal disease. Antibiotics are and protecting commensals. Actinomy-
only indicated where there is a risk of bacteraemia associated with perio- ces, Streptococcus and Pasteurella are
dontal bleeding. frequently isolated strains.

© Hervé Brissot
n The ratio between Gram-positive and
Treatment recommendations Gram-negative bacteria varies with the
n Non-antibiotic treatment: the basis of state of inflammation of the gingiva. In
treatment is the mechanical removal of healthy patients, Gram-negatives dom-
the periodontal plaque and ultrasound inate. With increasing inflammation Figure 2 - Severe dental plaque (calculus).
and periodontal disease, the ratio is in- The plaque is a solid biofilm which is not af-
descaling, flushing of gingival recesses fected by any kind of antibiotic.
and possibly dental extraction. versed1.
n Control of dental plaque is achieved n The oral cavity is a highly vascularised
by oral hygiene and tooth brushing. area, making it very resistant to infec- indicated in patients that:
tion with excellent healing properties • are immunocompromised,
n Antibiotics are not an alternative to
despite its high bacterial content. • are elderly or systemically ill,
plaque removal and descaling.
n Treatment of periodontal disease • have large or critical implants (e.g. hip
n Antibiotics may be considered to pre-
consists of hygiene with frequent tooth prosthesis, pacemaker, large non-re-
vent disorders secondary to bacterae-
© Hervé Brissot

brushing and occasional descaling with sorbable mesh).


mia possibly favoured by periodontal
treatment (see Prevention of infectious assessment of the gingival recess. An- n Patients with severe oral infection or
endocarditis, p.154). tibiotics are rarely needed. needing multiple extraction with obvi-
n Antibiotic therapy may need to be con- n However, any periodontal procedure ous concomitant osteomyelitis, patients
Figure 1 - Descaling and mouth hygiene are (descaling, extraction) is likely to be undergoing extensive oral surgery (e.g.
sidered after dental extraction and bone the only way to prevent development of peri-
curettage in case of alveolar osteomy- odontal disease. associated with bacteraemia. A short mandibulectomy/maxillectomy) are also
elitis due to severe periodontal disease. course of antibiotics may therefore be good candidates for antibiotherapy.

270 271
Periodontal disease

Reasoning
n Antibiotics effective against Gram-pos-
itive and anaerobic bacteria are used
as an antibiotic prophylaxis when per-
DISEASE FACT SHEETS

DISEASE FACT SHEETS


forming periodontal procedure. Intra-
venous medications are preferred and
are injected 30 to 60 minutes prior to
the procedure (cf. protocol for antibiotic

© Hervé Brissot
prophylaxis). Antibiotic therapy should
be discontinued 24 hours after the
procedure as there is no indication for
longer treatment unless specific condi-
tions (immunodepressed or elderly pa- Figure 3 - Chronic gingivitis and periodon-
tient) are involved. titis will lead to bone inflammation and in-
fection. Note the bone lysis around the teeth
n Culture and sensitivity testing is not root (pink arrows).
routinely performed.

Difficulties and particularities


n Long-term antibiotic treatment will Gram-negative and anaerobic bacteria.
affect the normal balance of the oral Usually amoxicillin+clavulanate or first
flora and is not recommended. generation cephalosporin can be used,
n Antibiotics should be given at the time possibly in association with metronida-
of an oral intervention to control the po- zole or clindamycin.
tential risks associated with transient n If indicated, post-operative antibiot-
bacteraemia or post-operatively to en- ic treatment should be given for 1 to 2
sure healing of the surgical site. weeks to allow mucosal healing.
n Antibiotics should be broad-spec- n See Bacteraemia (sepsis), p.158, if anti-
trum with a specific efficacy against biotic treatment is needed (risk of sepsis).

272 273
Part 2
REcommendations
RECOMMENDATIONS

274
RECOMMENDATIONS

RECOMMENDATIONS
Approach to a suspectED
bacterial infection

276 277
How do I sample for cytology in cases
R.1
of suspected bacterial infections? For cutaneous and subcutaneous nod- are then separated, 5 ml of air is aspi-
ules, the needle can also be moved back rated into the syringe, before needle and
and forth into the lesion in different di- syringe are connected again. Finally the
rections three or four times – without material is blown onto a glass slide by
releasing the negative pressure. Before rapidly pressing on the syringe plunger.
n A sample should be collected from avoided, as it leads to nuclear the needle is withdrawn from the lesion, In case liquid or abundant material is
tissues and organs whenever there is stripes (artefacts) and renders the negative pressure is released in or- deposited on the slide it can then gently
suspicion of a bacterial infection. The the sample unassessable. der to avoid the collected material enter- be spread with another glass slide, with
material collected should be as re- ing into the syringe barrel. The syringe the exception of pus, which should never
n The most suitable sampling proce-
RECOMMENDATIONS

RECOMMENDATIONS
presentative as possible of the lesion. and the needle (containing the sample) be streaked.
dure should be chosen depending on
n Preference should be given to the the organ or tissue sampled.
Fine needle insertion
quality and not to the quantity of the
cells collected, so that a thin, single cell n Stains should be fresh and free This technique is very useful for very to a syringe) is repeatedly inserted in
layer should be obtained with smears. from debris, as insufficient staining small solid lesions, if excessive bleeding the tissue, and connected afterwards to
Large amounts of clustered cells or foreign material can negatively in- is obtained by fine needle aspiration, and a syringe full of air, in order to blow on
are impossible to evaluate. Streak- fluence the evaluation of the cytologi- in the case of very delicate tissues and a glass slide the few cells collected by
ing of purulent material should be cal sample. cells, such as lymph nodes. A 21-22- capillarity into the needle.
gauge needle alone (i.e. not connected
Impression smears
Equipment Impression smears are useful in open
exudative lesions, greasy seborrhoeic
Required: • cotton swabs, transparent acetate tape, skin and from freshly cut surfaces of
• slides with frosted ends (in order to • staining liquids, extirpated tissues (e.g. skin nodules,
write on it the name of the patient and liver biopsies). With this technique the
• a good binocular microscope with 4, glass slide is simply pressed repeatedly
the origin of sample),
10, 40 and oil immersion (preferably (not streaked) on the lesion. In a simi-
• 5-10 ml syringes, 21 and 24 gauge planar or semi-planar) 100x objectives, lar manner, pus from pustules and un-

© DPM ENVN ONIRIS


needles, an adjustable light source and condenser. der crusts can be collected after gently
opening the pustules or lifting the crusts
Specimen collection with a small 25-gauge needle (Figure 1).
There are different cytological collection techniques, depending on the tissue, organ If extirpated nodules or pieces of tis-
and type of lesion. sue are cut for an impression smear,
it is advisable to dry the sectioned Figure 1 - For impression smears, the glass
Fine needle aspiration biopsy surface on paper before pressing it on
slide is pressed repeatedly, and not streaked,
on the lesion.
The fine needle aspiration (FNA) tech- For solid organ tissues, a 21-gauge the slide, in order to avoid excessive
nique is useful for nodules, plaques, tu- needle, connected to a 5 or 10 ml-syr- blood contamination of the cytological
mours, lymph nodes, solid organs (e.g. inge, is inserted into the centre of the preparation. The fresh section of the
spleen, liver) and cystic organs (e.g. lesion and a negative pressure of circa mass is then firmly applied to the glass
joints, bladder). 2 ml is applied. slide in several successive imprints.

278 279
How do I sample for cytology in cases
R.1
of suspected bacterial infections?

Scrapings
Suggested technique by lesion and organ
Superficial scrapings performed with a Skin
number 10 or 20 blade on greasy sebor-
Greasy skin: clear acetate tape, saline moistened cotton swab rubbing and rolling
rhoeic skin may be smeared on a glass
on a slide, superficial skin scraping and smearing on a slide.
slide, like “butter on bread”, in order to
look for bacteria or Malassezia yeasts. Pustules, collarettes, crusts: gentle impression sampling on material obtained
by opening a pustule or lifting a crust with a small needle. Do not streak pus!
Swabs Erosions, ulcerations, draining tracts: impression smear.
RECOMMENDATIONS

RECOMMENDATIONS
Papules and small nodules: fine needle insertion.
Material for cytology can be collected

© Chiara Noli
with a swab from fistulas, holes obtained Plaques and larger nodules: fine needle aspiration, cotton swab sampling from
after punch biopsies, ear canals or a holes obtained by punch biopsies (e.g. for bacterial culture or histopathology).
greasy skin surface, particularly in areas
where a direct impression smear with a Figure 2 - A cotton swab is a useful tool Ears
glass slide would be difficult to perform, for collection of material for cytological ex- Cotton swab sampling and rolling on a glass slide. Centrifugation of lavage liquid
e.g. skin folds or interdigital spaces amination of exudates from fistulas or skin from middle ear.
areas difficult to reach with a glass slide im-
(Figure 2). The swab is then gently rolled pression smear, such as interdigital spaces.
(not streaked!) across the slide. Sinus, bronchi and lungs
Centrifugation of lavage liquid from sinuses, nasal conchae, trachea, bronchi and
Adhesive tape alveoli. For highly cellular bronchi and alveoli samples, direct smears can be an
alternative to centrifuged samples.
Repeatedly pressing a strip of clear seborrhoeic material searching for sur-
adhesive (acetate) tape on the skin, face bacteria and Malassezia on the keratin Eyes
particularly on greasy areas, is a suit- scales. Adhesive tapes can be stained in Cotton swab sampling of the conjunctiva and cornea.
able technique for the collection of the same way as glass slides (see p.282).
Urine
Lavage Take a urine sample by cystocentesis preferably, or if not possible, from sponta-
This technique is useful for cavities and cavity to be sampled and re-aspirated neous micturition.
tubular organs, such as the middle ear immediately thereafter. Readers are
Bones and joints
and bulla, the respiratory and reproduc- referred to textbooks for the particular
Cotton swabs of a fistulous tract or from where a pin emerges or directly from
tive tract. Generally, a few ml of ster- methodology for each particular organ.
the orthopaedic implant (screw) after removal. Fine needle aspiration from joints,
ile saline solution are injected into the
liquid from articular lavage if performed during treatment.
Centrifugation of liquids Large cavities
Concentration by centrifugation should bottom of a conical tube (e.g. Eppendorf). The sample can be taken by aspiration using a syringe.
be considered for fluid samples with low The supernatant is eliminated and cells
cellularity. Centrifugation (speed as for are then resuspended in a small amount Solid organs
separation of serum) of specimens is used of the fluid remaining in the tube, which Fine needle aspiration.
to concentrate cells in a pellet at the is then put on a slide and smeared.

280 281
How do I sample for cytology in cases
R.1
of suspected bacterial infections?

Fixation and staining


All cytological samples have to dry on the Common rapid stains used in cytology
slide. Slides with greasy or waxy material include Romanowsky stains e.g. Diff
or specimens collected with a mois- Quik®, Hemacolor® (Figure 3). Samples
tened swab may be lightly heated on a are immersed 5-10 seconds each in eth-

© Chiara Noli
match or lighter flame before staining. anol (fixation), in the red stain and in the
blue stain.
RECOMMENDATIONS

RECOMMENDATIONS
Figure 4 - A clear adhesive tape is pressed onto greasy skin, stained as other cytological samples,
pressed on the glass slide and then excessive liquid is eliminated with a paper cloth.

After staining the slides are quickly as well as to replace liquids when ex-
rinsed under tap water and air-dried. pired or not performing as they should.
Adhesive (acetate) tape preparations can It is advised to reserve a staining set for
also be stained, rinsed and pressed to a otitis samples, as it often gets contami-
microscope slide with the sticky face on nated by cerumen and debris.
a b the glass slide (Figure 4).
Rapid stains are widely used by veterinar-
Rapid stain fluids should be changed ians in practice, however, they preclude
frequently, in order to avoid artefact pre- fine cytological analyses. Other stains
cipitates on the slides and to preserve may need laboratory equipment, such as
their staining capacity. It is important to Gram, PAS (Periodic Acid Schiff), May-
filter the liquids (a coffee filter will do) Gruenwald-Giemsa (MGM) and Ziehl-
and to clean the containers periodically, Neelsen (for acid-fast bacteria). n

© Chiara Noli

c d

Figure 3 - Romanowsky-type staining (e.g. Diff Quik®), easy to carry out in practice for rapid
cytology results. (a) From left, fixation liquid, red (eosinophilic) stain, blue (basophilic) stain.
(b) Samples are immersed 5-10 seconds each in ethanol (fixation), in the red stain and in the blue
stain. After staining, the slides are briefly rinsed under tap water (c) and air-dried (d). Adhesive
tape preparations can also be stained (sticky side on the glass slide).

282 283
How do I interpret cytology results
R.2
and how should I act upon them? Pseudomonas aeruginosa is able to
grow and multiply in eosin for up to
two weeks if the liquid is contaminat-
ed with organic debris. Liquid samples
that are not smeared immediately, and
n Use only samples that are repre- n Note that: are kept overnight at room tempera-
sentative of the disease or lesion and • negative samples do not ture before examination, can serve as a
of good quality. exclude infection, perfect culture medium for contami-
nants or bacteria present in the sample.
n Scan the cytology slide in a sys- • false positive samples are possible
This can lead to their presence or num-
RECOMMENDATIONS

RECOMMENDATIONS
tematic manner to identify the most (contamination, artefacts),
ber being greatly overestimated. It is

© Chiara Noli
representative and suitable fields to • the presence of intracellular bacte- thus very important to make one or more
be evaluated. ria, in neutrophils or macrophages, smears of the liquid for cytological ex-
is diagnostic of infection, amination immediately after sampling.
n Decrease the chances of false nega-
• the presence of bacteria outside or All laboratory material, such as glass-
tive or false positive findings by: in the absence of inflammatory cells ware and pipettes, should be clean, and
Figure 1 - Cytological appearance of a bac-
terial infection: bacteria are visible inside
• asking an expert cytologist to inter- can also be diagnostic of infection, disposable pipette tips should be used the cytoplasm of neutrophils. Note the swol-
pret the samples, however contamination or artefacts to prevent contamination. Staining solu- len degenerate nuclei of the neutrophils.
should also be considered in these tions should be filtered frequently or as (Diff Quik® 100x).
• use clean containers and fresh
staining liquids, cases. soon as foreign material is detected.
• immediate processing of the sample.

Significance of negative and positive cytological Methodology of the cytological examination


bacterial findings Slides should be evaluated in a sys- subsequent examination at a higher
tematic way under the microscope at magnification. The preparation should
Finding infectious agents in cytological types of preparations (e.g. wet-mounts
increasing resolutions (4x, 10x, 40x not be too thick and the cells should not
samples depends on the disease, lesion, or unstained urine sediment), then eval-
and 100x with oil immersion). Initially be broken or streaked. Only intact cells
organ, sampling and processing pro- uation of a stained sediment smear may
the cellularity and representativeness should be examined and evaluated. The
cedures and experience of the person be helpful to confirm this suspicion.
of the sample, the quality of the smear colour balance should be assessed: with
evaluating the slide.
Finding bacteria outside inflammatory and of the staining should be evaluated modified Wright stains, nuclei should be
Generally, the presence of bacteria cells can be diagnostic of infection, but it first at low power (4x). Groups of cells clearly blue and eosinophils should have
inside inflammatory cells (Figure 1), can also be the consequence of contam- are then identified at 10x, these cells are red-orange granules. If either colour
such as neutrophils or macrophages, ination or artefacts. Melanosomes, gran- later better observed at 40x and 100x. is too weak, the sample should be re-
is diagnostic of an infection. However, a ular precipitate, mast cell granules, gel Special attention should be given to the stained in fresh dyes. There should be
negative sample cannot exclude it. The (ultrasound, topical therapies) and debris feathered edge (if present), to the edg- no artefacts or dirt, such as in old bad-
probability of finding infectious agents can all resemble bacteria to the inex- es of the smear and within the smear to ly filtered and/or contaminated stains.
is obviously greater if the samples are perienced eye. Bacterial contamination detect unusual features that may need
evaluated by an expert cytologist. If of samples can occur if the staining
infectious agents are suspected in some liquids are not filtered and changed often.

284 285
How do I interpret cytology results
R.2
and how should I act upon them?

Interpretation of cytological samples Romanowsky type stains, they are ob-


served as “empty” spaces in the mac-
Once the quality and representativeness
rophage’s cytoplasm. Depending on
of the specimen have been evaluated, its
the mycobacterial species the number
nature should be determined.
of microorganism present can be very
In the case of inflammation, different variable. Ziehl-Neelsen stain can be

© DPM ENVN ONIRIS


immune cells such as neutrophils, eo- useful to identify them as acid-fast bac-

© Chiara Noli
sinophils, macrophages, lymphocytes teria, although a bacterial culture and/
and plasma cells are observed, while in or a PCR will be needed for the precise
RECOMMENDATIONS

RECOMMENDATIONS
neoplastic samples, cellularity is usual- definition of the mycobacterial species.
ly more phenotypically homogenous.
In cutaneous and otic samples large Figure 3 - Cytological appearance of bacterial
Where inflammation is due to bacteri- Figure 2 - Staining liquids must be filtered numbers of cocci or rods, in the ab- overgrowth: numerous rods in the absence
and changed often to avoid any bacterial of inflammatory cells (Diff Quik®, 100x).
al infection, neutrophils and/or mac- sence of inflammatory cells, can be ob-
contamination of samples.
rophages are the main inflammatory served and are diagnostic of bacterial
cells to be expected and microorgan- overgrowth (Figure 3). These conditions without inflammatory cells are observed
isms may be observed in intra or extra- aggregates and the latter align in a linear should be treated topically with antisep- in specimens of organic fluids, then
cellular positions. Signs of cell degener- pattern. tics rather than systemically with anti- contamination and post-sampling bac-
ation can be observed, such as nuclear biotics (e.g. if large numbers of bacteria terial growth should be considered). n
In cases where intracellular staphylo-
swelling, karyorrhexis and karyolysis.
cocci are seen, and the animal presents
Some microorganisms (such as pyogen-
with a first occurrence, previously un-
ic bacteria) elicit a neutrophilic infiltrate,
treated and uncomplicated infection,
others (such as some mycobacteria), a
the choice of an empirical antibiotic
mainly macrophagic (granulomatous)
(such as amoxicillin±clavulanic acid or
or pyogranulomatous (a mixture of neu-
cefalexin) is acceptable, as suscepti-
trophils and macrophages) infiltrate.
bility patterns of staphylococci are well
Knowing the inflammatory pattern typ-
known.
ical for each organ and disease is of
great diagnostic help. However, as cytological identification
of the bacterial species in case of rods
Finding bacteria inside neutrophils is
is not possible, a bacterial culture and
diagnostic of pyogenic infections, such
susceptibility test will be needed for the
as those caused by Staphylococcus,
choice of an effective antibiotic.
Streptococcus, Pseudomonas, E.coli,
Klebsiella, Proteus, Pasteurella or Coryne- Bacteria contained in macrophages
bacterium. In these cases, neutrophils usually belong to the genus Mycobac-
are usually young (e.g. with 2-3 nuclear teria, Nocardia, Actinomyces and Act-
lobes) and show obvious signs of de- inobacillus. Actinomyces and Nocardia
generation, such as nuclear swelling. can also be seen as clumps of baso-
Staphylococci can be differentiated from philic filamentous rods. As mycobacteria Figure 4 - Cutaneous and otic bacterial overgrowth should be treated topically with antiseptics
rather than with antibiotics.
streptococci in that the former form are acid-fast and do not take up rapid

286 287
RECOMMENDATIONS

288
Bacteriology

289

RECOMMENDATIONS
When is culture and sensitivity
testing of little use, recommended,
R.3
In some patients the negative effects results may be clinically irrelevant and
indispensable? caused by the minimally invasive proce- lead to inappropriate or unnecessary
dures required for sampling may exceed antimicrobial therapy based on the re-
the positive effects derived from culture. sistance profiles of commensal strains1.
Contraindications and disadvantages The clinical significance of sensitivity
n Culture and sensitivity testing is n Culture and sensitivity testing of minimally invasive abdominal and testing is questionable for infections that
contraindicated for: is recommended in the following thoracic surgical procedures have been
situations: require topical antimicrobial therapy be-
• Infections that require minimally in- reviewed by Lansdowne et al.2. cause clinical breakpoints do not have
vasive sampling procedures if: • if there is suspicion of a compli-
If no laboratory methods exist for de- any clinical predictive value when antimi-
RECOMMENDATIONS

RECOMMENDATIONS
cated infection (e.g. associated with
- collection of the sample may com- tection of the suspected pathogen (e.g. crobial drugs are applied locally. This is
underlying disease),
plicate an acute infection (e.g. thora- use of selective media or molecular because the drug concentrations achieved
• if there are rods in cytology,
coscopy in case of pneumonia), diagnostic methods), culture of biolo- at the infection site by topical therapy
• if the patient has not responded to
- the patient suffers from abnormal therapy, gical specimens containing commensal are much higher than those obtained in
clotting, or • if the patient has a history of re- bacteria is contraindicated because the serum after systemic administration.
- anaesthesia poses a high risk to lapse or re-infection,
the patient, especially when the risk • if there is any reason to suspect
of contamination with commensal infection with MDR bacteria.
bacteria is high (e.g. bronchoalveo-
lar lavage). n Culture and sensitivity testing is
• Infections for which correct inter- indispensable in the following situa-
pretation of the culture results is tions:
hampered by the normal presence of • if the patient is immunocompro-
commensal flora in the sample (e.g. mised,
faeces and nasal or vaginal swabs) • if the infection is life-threatening.
unless the suspected pathogen may
be cultured by selective media or de- n Empirical therapy while awaiting
tected by specific molecular tests. the results from the laboratory is
highly recommended for life-threate-
n Culture and sensitivity testing is of ning infections, immunocompromised
little use for those infections that are patients as well as for any infections
managed topically such as otitis ex- causing pain or discomfort that can-
terna and wound infections. not be easily relieved by non-anti-
biotic medication. Where possible,
cytology can be used to try and guide
empirical treatment choices. Appearance of a primary culture contaminated with commensal bacteria. The presence of com-
mensal bacteria is a major contraindication for culture of non-sterile biological specimens such
as faeces and nasal or vaginal samples. Diagnostic processing of non-sterile biological speci-
mens is only indicated if culture is aimed at detecting specific organisms for which selective
media or molecular diagnostic methods are available.

290 291
When is culture and sensitivity testing of
R.3
little use, recommended, indispensable?

Culture and sensitivity testing is recom- This is why culture and sensitivity testing
mended when: should be accompanied by empirical
• there is a high risk that empirical anti- therapy in all situations where a delay
microbial therapy may fail due to anti- in the start of the therapy may have a
microbial resistance, deleterious impact on animal health and
• failure of therapy may lead to possible welfare. In these situations the results
complication, or of sensitivity testing can be usefully
• in case of life-threatening infections employed to correct the therapy if the
or immunocompromised patients where cultured strain is reported as resistant
culture and sensitivity is regarded as in- to the antimicrobial used for empirical
RECOMMENDATIONS

RECOMMENDATIONS
dispensable because there is a high risk treatment. It is the responsibility of the
that therapy failure may result in serious clinician to decide whether empirical
health consequences for the patient.
Judicious antimicrobial use should not
therapy can be avoided based on the
clinical conditions of the individual pa- Taking and
impact best practices in patient care. tient. n
sending samples

292 293
How should samples for bacterial
culture and antibiotic sensitivity
R.4

testing be taken (correctly)?

n As a matter of principle samples contamination from the com-


should be taken from a location where mensal bacteria inhabiting skin
the infection is active. and mucosae.

n Particular precautions should be


RECOMMENDATIONS

RECOMMENDATIONS
n Sample types and techniques de-
taken when collecting sterile spe- pend on the infection site.
cimens (urine, blood, etc.) to avoid

Skin
Superficial or surface pyoderma
Sampling for bacterial culture from su- swab can be rubbed along the edges of
Good quality sampling is the condition for a good bacteriological analysis.
perficial lesions is ideally performed by a collarette, from under a crust or from
opening an intact pustule and collecting open exudative lesions. Samples from
the pus with a sterile cotton swab. In the seborrhoeic skin can be collected by guidance. Care must be taken that the ear infection with an intact tympanic
absence of intact pustules, the sterile vigorous rubbing with a swab. swab does not come in contact with the membrane. This procedure should be
skin of the vertical ear canal. A myrin- performed by an expert dermatologist
Deep pyoderma gotomy is necessary in case of middle or otologist.
Sampling for bacterial culture from face of deep lesions should always be
deep lesions should ideally be perfor-
med by fine needle aspiration from the
disinfected prior to sampling. It is im-
portant not to use a persistent disinfec-
Osteo-articular system
depth of a lesion or by skin biopsy, after tant (such as chlorhexidine) and to allow Osteomyelitis and post-surgical infection
surface disinfection. Collecting exudate the alcohol to evaporate before collec- Do not sample a discharging tract (pus be useful. The best sample is a surgi-
expressed from the depth of a lesion by ting the sample. is often sterile and contaminated by cal biopsy of the necrotic bone and/
squeezing it is also acceptable. The sur- skin flora). Ultrasound-guided fine nee- or culture from the infected implant
dle aspiration of the surgical site may (screw/suture).
Infected wounds and abscesses
Do not sample a discharging tract (pus a biopsy punch or cold blade. For ab- Septic arthritis
is often sterile or contaminated by skin scesses, sample the abscess capsule. Do not sample a discharging tract (pus fluid directly (immediately) placed in
flora). Tissue biopsy is preferred with is often sterile and contaminated by skin a blood culture vial. Consider surgical
flora). Sterile aspiration of the synovial biopsy of the synovial capsule.
Otitis
For culture samples from the vertical For samples from the horizontal ear ca- Periodontal disease
canal, a sterile cotton swab is simply in- nal or from the bulla, the animal has to Sampling is rarely performed. In case of Consider conditions for possible anaer-
serted in the ear. This can be performed be anaesthetised and sampling should severe osteomyelitis, a surgical biopsy obic culture.
without sedation in most animals. be performed under video-otoscopic of the infected bone might be indicated.

294 295
How should samples for bacterial culture and
R.4
antibiotic sensitivity testing be taken (correctly)?

Urogenital system Eyes


Urine Conjunctivitis & Keratitis
Samples are taken preferably by cysto-

© Salvador Cervantes
Samples for cytology/AST should be be taken before applying local anaesthet-
centesis or via sterile catheter, or if not taken before applying any stain (e.g. ics, their use probably does not modify
possible, from spontaneous micturition. fluorescein or Bengal rose). Conjuncti- cell morphology or culture results. In cats,
val/corneal cotton swabs are commonly a sample should be set aside for viral/
Mastitis used. Although, ideally, samples should chlamydial/Mycoplasma DNA detection.
A milk sample can be obtained manually
Cystocentesis in a cat. Uveitis
or by direct aspiration from the gland for
RECOMMENDATIONS

RECOMMENDATIONS
cytology and culture & AST. Samples for sensitivity testing are not recommended instead.
very useful. A complete blood work is
Endometritis/pyometra
Fluid for bacterial culture and sensitivity nial vaginal sample can be obtained by
testing is collected transcervically from using a speculum and a guarded swab.
the uterus. If this is not possible, a cra-
Vaginitis

© Salvador Cervantes
A urine sample should be obtained by cytology and culture should be perfor-
cystocentesis for urinalysis, culture and med using a speculum and a swab.
sensitivity testing, Furthermore, vaginal
Prostatitis
Sampling for prostatitis is made by cysts are detected during ultrasonogra-
passing a urinary catheter (aseptically phy then a FNA is a good option for sam- Eye sampling in a cat using a cotton swab.
placed) to the level of the prostate and pling. In some cases, culture of a biopsy
massaging the gland to obtain fluid. If sample is required. Respiratory system
Epididymitis/Orchitis Rhinitis
Culture of semen is the preferred tech- testicles can be performed but false neg- Bacterial culture and sensitivity testing culture and sensitivity tests are required,
nique. However, it may be a challenge ative results are quite common. of nasal swabs or nasal discharge are nasal biopsies or a (deep) nasal flush
to obtain a good sample. FNA from the not recommended. Fungal cultures of should be performed. If Mycoplasma
nasal biopsy samples can be indicated if infection is suspected, special culture
Digestive system primary fungal infection is suspected. If media or PCR testing are necessary.

Stools Tracheobronchitis (dogs)


Intestinal bacterial infections are quite cultured in less than 24 h. A stained If dogs do not respond to empirical gy, quantitative culture, and sensitivity
rare. Take a stool sample using a faecal faecal smear has little to no diagnostic antibiotic therapy, tracheal or bron- testing. If Mycoplasma or Bordetella
loop or from the litter box (without lit- value for the diagnosis of bacterial as- choalveolar lavage (blind or endoscopic infection is suspected, special culture
ter contamination) and store as quickly sociated diarrhoea. sample) or transtracheal wash is in- media or PCR testing are necessary.
as possible at 4ºC. Samples should be dicated to obtain material for cytolo-

296 297
How should samples for bacterial culture and
R.4
antibiotic sensitivity testing be taken (correctly)?

Pneumonia Pyothorax
Bronchoalveolar lavage (blind or endo- ing. If Mycoplasma or Bordetella infec- Sterile pre-surgical samples of pleu- a blood culture vial. Observe the condi-
scopic sample) or transtracheal wash is tion is suspected, special culture media ral fluid obtained by thoracocentesis tions required for both aerobic and
indicated to obtain material for cytology, or PCR testing is necessary. or in-surgery samples of necrotic tis- anaerobic culture.
quantitative culture, and sensitivity test- sue should be (immediately) placed in

Other
Whole blood
RECOMMENDATIONS

RECOMMENDATIONS
In case of bacterial endocarditis or bac-
teraemia, take 2-3 blood samples at two
separate sites.
Septic peritonitis
Sterile pre-surgical samples of abdom-
inal fluid obtained by paracentesis or
in-surgery samples of necrotic tissue
should be (immediately) placed in a
blood culture vial. Consider the condi-
tions required for both aerobic and an-
Cat blood sampling.
aerobic culture. n
© Bianka Schulz

Blind bronchoalveolar lavage procedure in a cat to obtain material for


cytology, culture and sensitivity testing. Sterile sodium chloride solu-
tion (0.9%) is applied into the lower airways over a sterile catheter
inserted into a sterile endotracheal tube and recovered via collection
tube and mechanical suction.

298 299
Is it useful to take a sample in animals
R.5
undergoing antibiotic treatment? Monitoring of outcome
Monitoring of the bacteriological out- the initial 72 h of antibiotic treatment
come during therapy is also recom- could be predicted on the basis of
n It may be useful to take a sample n Whenever possible, culture mended for specific infections requiring pre-antibiotic blood cultures1.
during or immediately after the end should be combined with cytol- long courses of antibiotic treatment, In any case the microbiology laboratory
of antibiotic treatment in those situ- ogy or other means of determining such as upper urinary tract infections should be informed if a sample has been
ations where: inflammation/infection when evalu- and pyoderma2,3. In these patients, the collected during or shortly after antimi-
• culture and sensitivity testing are ating patients undergoing antibiotic purpose of this recommendation is to crobial therapy, so that this factor is tak-
RECOMMENDATIONS

RECOMMENDATIONS
recommended or indispensable (see therapy. minimise the risk of relapse and the en into account in the report.
recommendation R.3) but a sample negative consequences of treatment To confirm a bacteriological cure, sam-
was not collected prior to the start of n It is not useful to take another failure. ples are occasionally taken during
antibiotic treatment (e.g. some refer- sample if the patient is responding Culture of samples taken during anti- antibiotic treatment. In a non-sterile
ral cases), to therapy, in those situations where biotic treatment is unlikely to provide environment, the culture may still be
a sample was collected prior to the new information compared to samples positive due to contamination by com-
• there is clinical or paraclinical
start of treatment or culture is of lit- collected before treatment. A study in mensal bacteria. In that case, the deci-
evidence of infection/inflammation
tle use (see recommendation R.3). human medicine showed that blood cul- sion to stop treatment should be guided
indicating that the patient is not re-
sponding to empirical treatment, tures taken from human patients during by cytology results and clinical signs. n
• the clinician wants to evaluate
the efficacy of therapy during a long
course of treatment or before cessa-
tion of therapy.

Ideally, samples for culture should be pact patient care. In fact, if a pathogen
taken before antibiotic treatment to is inhibited by the presence of antibiotic
avoid results that are affected by the residues in the specimen, it means that
presence of antibiotic residues in the the organism is susceptible and therapy
sample. However, culture of samples is likely effective.
collected during therapy does not im-

Sampling during therapy


It is advised to take a sample during ture results provide useful information
therapy in those cases where sensitiv- on whether therapy should be discon-

© Vebio
ity testing is recommended or indis- tinued (positive culture) or not (negative
pensable (see recommendation R.3) culture) based on bacteriological cure,
or if a sample was not taken prior to the thereby limiting the negative conse- Swab and agar bottle.
start of therapy and no clinical improve- quences on animal health associated
ments are observed 3-5 days after the with treatment failure.
start of therapy. In these cases, the cul-

300 301
What information should be supplied
with the sample? Where should the
R.6
It remains the veterinarian’s responsi- licence and species indications for the
sample be examined? bility to check on the summary of prod- drug used.
uct characteristics (SPC) regarding the

n Information that should be supplied


with the sample:
• information on antimicrobial
therapy (with dose, duration and
Impoving standards and reporting
• patient name or identification number, drug), This situation shall be improved by set- testing should be interpreted by the lab-
• patient species, age and sex, • type of culture and tests requested. ting clear rules and minimum quality oratory using urine-specific breakpoints
RECOMMENDATIONS

RECOMMENDATIONS
• name and full address of the clinic standards for diagnostic licensing as if the strain is cultured from the lower
n Where should samples be sent for well as by establishing continuing ed- urinary tract (e.g. cystitis)1.
submitting the sample,
examination: ucation to train laboratory personnel. Information on the time of sampling is
• name and phone/e-mail contact of
the veterinarian in charge, • samples should be analysed by an Some veterinary clinics may use rap- particularly important for urine samples,
appropriate human or veterinary di- id in-house bacteriological diagnostic which should be processed within 24
• sample type,
agnostic laboratory, tests for which limited information is hours unless transported under spe-
• body site from which the sample
• human laboratories can be used if available regarding their validity. Anal- cific conditions (see recommendation
was collected,
they are qualified in processing ani- ysis by a qualified laboratory should be R.7).
• date of sample collection, mal samples, preferred.
• clinical diagnosis and any relevant It is useful to include as much history of
• rapid in-house bacteriological The sample ID number is particularly the case as possible, so that the labo-
history (e.g. suspected relapse, rein- diagnostic tests exist, but little infor- important when multiple specimens ratory can suggest the most appropriate
fection or concurrent conditions), mation is available regarding their are submitted from the same patient. culture (e.g. anaerobic culture, culture
• cytological findings (if relevant), validity. The diagnostic laboratory cannot re- on selective media or ELISA tests for de-
port culture and sensitivity results for tection of clostridial toxins or PCR tests
Veterinary diagnostic laboratories usually in the content of the form. Even if the each individual sample if this informa- for identification of specific organisms),
provide request forms to collect this in- methods used for culture and sensi- tion is not provided by the veterinarian. in pursuit of a particular diagnosis. n
formation. tivity testing of human and veterinary Antibiotic efficacy is influenced by the
If the request form does not contain pathogens are the same, veterinary infection site. Thus, information about
sections where this information can be diagnostic laboratories should be pre- the sample type and the body site from
included, the veterinarian should not ferred because some pathogens, anti- which the sample originates facilitates
hesitate to contact the diagnostic lab- biotics and clinical breakpoints are vet- guidance on rational antibiotic choice by
oratory to propose possible changes erinary specific. the diagnostic laboratory. For example,
first-generation cephalosporins are not
Laboratory examination factors to consider recommended for central nervous system
infections due to the poor penetration of
The most important factor in deciding could be performed by non-specialized the blood-brain barrier, whereas clin-
where the sample should be sent is the laboratories that are not adequately damycin has good penetration into bone
proficiency and expertise of the recipi- equipped and trained to perform and and fluoroquinolones achieve high con-
ent microbiology laboratory. Diagnostic interpret such tests. The use of human centrations in the prostate2. Ampicillin Complete patient information should come
licensing for sensitivity testing is gen- laboratories may result in reports indi- and amoxicillin/clavulanate concentrate with the sample.
erally not regulated and sensitivity tests cating the use of human drugs. in urine and the results of sensitivity

302 303
How should samples be transported?
R.7

Cushioning material Documents Absorbent


(expanded polystyrene which go with the sample substance
foam , …). (attach here) in sufficient quantity
Refrigerant gel to absorb the
if necessary sample if needs be
n The specimen should always be n Samples for anaerobic culture (absorbent padding,
placed in a container designed to should be transported in specific flannel cloth, ….)
prevent leakage and potential safety transport tubes (ask laboratory).
hazards. Transport medium
n Urine samples should be refriger- Third layer of with sample
RECOMMENDATIONS

RECOMMENDATIONS
First leakproof
n The packaging and method of car- ated immediately after collection and packaging
receptacle
(solid case which can be
riage should conform to any existing delivered to the laboratory as quickly tightly closed: wood, (tube, flask
relevant national or international reg- as possible and within 24 hours. Al- metal, cardboard, or sealed phial,
plastic, …) with thick sides)
ulations. ternatively, samples can be trans-
ported under refrigerated conditions
n The container should be labelled to Put on the outside of the package the
(ask laboratory), using urine preserv- address of the laboratory it is being sent to
indicate the sample ID. as well as the sender’s details Second leakproof
atives or processed in the clinic using

73
(with telephone and fax n°s) packaging

33
n The use of tubes containing transport point-of-care tests. (resistent thick plastic

N
Use a label like the one
medium is recommended for swabs or metal case)

U
in the example here:
sent via regular mail or otherwise not BIOLOGICAL SUBSTANCE,
CATEGORY B
processed within 24 hours after col-
lection. Figure 1 - Simplified diagram of a triple package (according to standards of class 6.2 of the UN).

Common bacterial pathogens in com- Transport of urine requires particular


panion animals are non-fastidious or- attention because urine is analysed by
ganisms, generally not sensitive to the quantitative microbiology for the detec-
conditions of sample transport. Various tion of clinically significant bacteriuria.
brands of tubes or vials for collection It is therefore essential that the bacterial
and transportation of anaerobic speci- concentrations in the sample are not
mens are commercially available. They influenced by transport conditions such
are designed to protect anaerobic bac- as time and temperature.
teria from exposure to toxic amounts of
oxygen until the specimen is processed Certain international guidelines recom-
in the laboratory (Figure 1). Specific mend caution in the interpretation of A B C
products exist for transport of spec- results and retesting if transportation of Figure 2 - Growth on Flexicult Vet of Escherichia coli at different concentrations: 103 CFU/ml
®

imens to be tested for culture of other refrigerated urine samples exceeds 24 (A), 104 CFU/ml (B) and 105 CFU/ml (C). The agar medium of Flexicult® Vet contains chromogenic
medium for bacterial identification and is divided into five compartments for antimicrobial suscep-
fastidious organisms such as Mycoplasma. hours without urine preservatives3. tibility testing and one compartment for semi-quantitative bacterial enumeration.

304 305
How should samples be transported?
R.7

To avoid the cost of transportation un- are adequately trained to interpret


der refrigerated conditions, urine can the results and that clinics meet min-
be inoculated onto commercial “uri- imum standards to operate in-house
nary paddles” for in situ culture and culture. n
submitted to the laboratory if growth
is displayed after incubation (Figure
3). This approach has been suggested

© Rosmarie Voegtli, Flickr


to save the costs for laboratory analy-
sis of sterile samples 2.
RECOMMENDATIONS

RECOMMENDATIONS
Recently another point-of-care test
has been developed and validated for
detection, identification and antimi-
crobial susceptibility testing of bac- Interpretation
terial uropathogens in small animal
veterinary practice1. Use of this test Figure 3 - Urine can be inoculated onto
commercial “urinary paddles” for in situ
of results
(Flexicult® Vet, Figure 2) avoids prob- culture and submitted to the laboratory if
lems related to transportation of urine growth is displayed after incubation.
samples, provided that clinical staff

306 307
How should results be interpreted? Is the
classification ‘‘sensitive, intermediary,
R.8
The intermediate category is also used
resistant’’ predictive of the clinical efficacy? as a buffer to reduce the risk of false pos-
itive or false negative results. The latter
type of error (i.e. reporting a resistant
n If the strain is reported as suscep- inhibited by drug concentrations strain as susceptible) may have a great
tible (S), the antibiotic is an appropri- achieved in plasma after stand- impact on patient care, since the veteri-
ard dosage. narian can be induced to choose a drug
ate choice for treatment because the
that is not effective against the strain
strain is inhibited by drug concentra- n In vitro sensitivity tests are not in-
causing infection. False positive results
tions achieved in plasma following
RECOMMENDATIONS

RECOMMENDATIONS
fallible and may have little clinical (i.e. reporting susceptible strains as re-
standard dosage. predictive value under specific cir- sistant) induce the veterinarians to un-
cumstances (see recommendation necessary use of second-line antibiotics.
n If the strain is reported as interme-
R.9). Figure 2 - Bacteria colonies on petri dish.
diate (I), the antibiotic may be effec-
tive if administered at a higher dosage n A correct interpretation of the re-
sults requires specific knowledge on
for concentration-dependent antibi-
otics (e.g. fluoroquinolones), or if it
the susceptibility to specific antimi- Sensitivity reports, difficulties
crobial classes/drugs used in clinical Interpretation of sensitivity reports
is used to treat infections at specific
practice (or the presence of resist- from diagnostic laboratories is com-
body sites where antibiotics concen-
ance). plicated by the inclusion of antibiotics
trate (e.g. urine, topical application).
n Based on the susceptibility results, that are not used in clinical practice,
n If the strain is reported as resistant clinicians should prefer first-line an- namely surrogate drugs that are used
(R), the antibiotic is not recommended tibiotics and de-escalate whenever to predict the efficacy of other antibi-
for treatment because the strain is not possible (see recommendation R.11). otics belonging to the same class (e.g.
sulfamethoxazole predicts susceptibil-
Goals of sensitivity testing ity to sulfadiazine) and drugs used for
detection of specific resistance pheno-
The goal of sensitivity testing is to pre- circumstances (see recommendation R.9). types of clinical relevance. Among the
dict the clinical success or failure of the latter drugs, oxacillin and cefoxitin are
antibiotic being tested against a particu- used for detection of meticillin resist-
lar bacterial strain. Strains tested are ance in staphylococci due to their abil-
classified by the laboratory as S, I or R ity to induce the meticillin resistance
based on clinical breakpoints, which are gene mecA under laboratory conditions.
defined by modelling of pharmacody- Strains resistant to oxacillin/cefoxitin
namic and pharmacokinetic data. Only should be regarded as resistant to all
Correct interpretation of the results requires
very few veterinary breakpoints are con- ß-lactams used in veterinary medicine. specific knowledge on the susceptibility to
© VEBIO

firmed by clinical outcome studies. Table 1 provides practical information specific antimicrobial classes/drugs used in
Although this classification is predictive on how to interpret results for common clinical practice.
of clinically efficacy, in vitro sensitivity Figure 1 - Culture and sensitivity testing using
antibiotics used for sensitivity testing.
tests are not infallible and may have little the disk method.
clinical predictive value under specific

308 309
How should results be interpreted? Is the
classification ‘‘sensitive, intermediary, resistant’’
R.8
predictive of the clinical efficacy?

Table 1 - Drug-specific interpretations of antibiotic sensitivity results. Modified from Jessen et al. 2012. Table 1 (continued)

Antibiotic Interpretation of sensitivity results Antibiotic Interpretation of sensitivity results


It predicts susceptibility to amoxicillin in all bacterial species It may be used to predict susceptibility to other veterinary
Ampicillin
and to penicillin in Gram-positive cocci. Enrofloxacin fluoroquinolones even though drug-specific breakpoints are
available for marbofloxacin and difloxacin.
It may be used for detection of extended-spectrum
ß-lactamase (ESBL) in Gram-negative bacteria due to its It predicts inducible resistance to lincosamides in
Amoxicillin
capacity to inhibit the activity of these enzymes, Erythromycin staphylococci. Lincosamides (lincomycin and clindamycin)
RECOMMENDATIONS

RECOMMENDATIONS
clavulanate
i.e. ESBL-producing strains are sensitive if they do not carry should not be used if the strain is resistant.
other types of ß-lactamases.
Sensitivity results cannot be used to predict the clinical outcome
It may be used to predict susceptibility to first generation of topical therapy. Interpretation using the human breakpoint
cephalosporins (e.g. cefalexin and cefadroxil). Fusidic acid
Cefazolin or is not recommended since the drug is used systemically in
Cefalexin-specific breakpoints are now available for testing human medicine and topically in veterinary medicine.
cefalotin
staphylococcal susceptibility to this drug, widely used for
treatment of canine pyoderma. Sensitivity results cannot be used to predict susceptibility to
other aminoglycosides (e.g. amikacin). Interpretation using
It is used for detection of meticillin-resistant Staphylococcus Gentamicin
the human breakpoint is not recommended when the drug
aureus (MRSA) and Staphylococcus pseudintermedius (MRSP). is used topically.
Meticillin resistance indicates that the strain is resistant to all
Cefoxitin ß-lactam antibiotics (penicillins and cephalosporins). It predicts susceptibility to clindamycin in Gram-positive
Lincomycin
It can also be used for detection of ESBL-producing strains, bacteria (not active against Gram-negative bacteria).
which are sensitive unless they contain another type of Second-line drug for treatment of urinary tract infections (UTIs)
ß-lactamase. caused by multidrug-resistant strains. It can only be used for
Nitrofurantoin
management of UTIs because it is rapidly excreted and
It may be used to predict resistance to other third generation
Cefotaxime or concentrates in urine.
cephalosporins, which is the main phenotypic trait of
cefpodoxime
ESBL-producing strains. It is used for detection of MRSA and MRSP. Meticillin resistance
Oxacillin indicates that the strain is resistant to all ß-lactam antibiotics
Sensitivity results cannot be used to predict clinical outcome
Cefovecin (penicillins and cephalosporins).
because there are no approved clinical breakpoints.
Second-line drug for treatment of infections caused by multi-
It predicts susceptibility to lincomycin in Gram-positive
Clindamycin drug-resistant strains. It should only be used in combination
bacteria (not active against Gram-negative bacteria). Rifampicin
with another drug because resistance can easily develop during
Second-line drug for treatment of infections caused by therapy by mutations.
Chloramphenicol multidrug-resistant strains such as MRSA/MRSP and
ESBL-producing strains. Tetracycline It predicts susceptibility to doxycycline in staphylococci.

It may be used to predict susceptibility to veterinary It predicts susceptibility to all sulphonamides in all bacterial
Sulfamethoxazole
Ciprofloxacin fluoroquinolones even though drug-specific breakpoints species.
are available for enrofloxacin, marbofloxacin and difloxacin.

310 311
How should results be interpreted? Is the
classification ‘‘sensitive, intermediary, resistant’’
R.8
predictive of the clinical efficacy?

Back to basics Clinical category limitations


The limits of clinical categories are de- differ from one country to another. The
Interpreting microbiological results used5 to interpret in vitro sensitivity
fined by critical values or breakpoints. Clinical and Laboratory Standards In-
starts by identifying the isolated bac- tests: Sensitive (S), Resistant (R) and
Two critical concentrations can be de- stitute has defined a large number of
teria, followed by a bacterial count (to Intermediate (I):
fined: the lower critical concentration critical values for species of veterinary
distinguish colonization from infec- • S strains are those for which the
c and the upper critical concentration interest1.
tion) and lastly by culture and sensitiv- probability of treatment success is
ity testing (C&ST). C (the corresponding critical diameters In 2009, in the United States, specific
high, in case of systemic treatment at
are d and D) (Table 2). critical concentrations only existed for
C&ST assesses the in vitro activity of the recommended dosage,
dogs, for3:
RECOMMENDATIONS

RECOMMENDATIONS
antibiotics against a bacterial strain • R strains are those for which there is The terminology used to describe crit-
responsible for an infection and helps ical values is complex and ambiguous, • enrofloxacin,
a high probability of treatment failure,
to guide the clinician’s therapeutic ap- whatever the type of treatment and the because it corresponds to several dif- • difloxacin,
proach. antibiotic dose, ferent approaches2 (Table 3). Critical values • marbofloxacin,
Culture and sensitivity results can be • I strains are those for which the effect
reported quantitatively, using mini- of treatment is unpredictable. These Table 3 - Critical values: terminology 2.
mum inhibitory concentrations (MIC) strains may have a resistance mecha-
(μg/mL or mg/L) or indirectly, through nism whose in vitro expression is low. This approach is based on the distribution, for the same bacterial
the measurement (in mm) of inhibition However, resistance to treatment can species and outside the clinical context, of MICs of wild strains
diameters (diffusion test). MIC is the appear in vivo. and of resistant strains. Ideally the two populations are clearly
best measure of in vitro antibacterial distinct and the concentration dividing these two populations is
Conversely, these intermediate strains
effect. defined as the epidemiological cut-off value.
may also show resistance in vitro that is
Epidemiological Epidemiological cut-off values are used as the most sensitive
Inhibition zones can be interpreted on insufficient to be classified as resistant method of measuring the development of resistance. They alert
cut-off values
the basis of critical diameters if these but low enough to expect treatment suc- microbiologists on sensitivity variations or pathogens.
are known. If not, the indirect estima- cess under certain conditions (high local They are totally independent of antibiotic dosages. A bacterium
tion of the MIC must be done with care concentrations or increased doses). is considered resistant if it tolerates in vitro concentrations
because of the lack of available data in Category Intermediate (I) is also a “buff- higher than those tolerated by the majority of strains of the
veterinary medicine. er” zone, to avoid interpretation bias same species.
Results can also be reported quali- related to technical or biological uncon-
A bacterium is considered sensitive if the antibiotic concentration
tatively. Three clinical categories are trolled uncertainties.
in serum is higher than the MIC. In these cases, antibiotic
Clinical treatment is considered clinically effective. This is no longer
Table 2 - Critical values: criteria of categorisation (according to the Antibiogram Committee of the breakpoints about differentiating sensitive from resistant bacteria from a
French Microbiology Society, 2010).
microbiological viewpoint, but to differentiate treatable and
Category MIC category (mg/L) Diameter (ø) (mm) non-treatable infections using antibiotics.
Sensitive MIC ≤ c ø≥D This approach takes into account pharmacokinetics (PK) and
PK/PD pharmacodynamics (PD) in order to estimate the clinical
Intermediate c < MIC ≤ C d≤ø<D breakpoints response to treatment.
Resistant MIC > C ø<d
c: lower critical concentration; C: upper critical concentration;
d: upper critical diameter; D: lower critical diameter.

312 313
How should results be interpreted? Is the
classification ‘‘sensitive, intermediary, resistant’’
R.8
predictive of the clinical efficacy?

• gentamicin, from inhibition diameters, defining the


• cefpodoxime proxetil, limit between sensitivity and resistance
• ampicillin (only for urinary infections), with a predefined error margin5. In vet-
• clindamycin. erinary medicine, the estimation of an
In France, a specific veterinary culture MIC from an inhibition diameter is diffi-
and sensitivity working group within the cult because of the lack of data.
Antibiogram Committee of the French In the field of companion animal infec-
Microbiology Society (SFM) establishes tious diseases, no studies have been
critical values (MIC and inhibition diam- carried out to establish a relationship
RECOMMENDATIONS

RECOMMENDATIONS
eters) on the basis of epidemiological between the efficacy of an antibiotic
thresholds. treatment and the result of culture and
However, the results of clinical studies, sensitivity testing.
dosing regimen and the pharmacokinetic The predictive value of culture and
(circulating and tissue concentrations) sensitivity testing in terms of clinical
and pharmacodynamic characteristics efficacy is only relative, for a number
of the antibiotic in the target species are of reasons:
not taken into consideration4. • Continued in vitro exposure of a limited

© VEBIO
An alternative to MICs consists of meas- number of bacteria to a constant antibi-
uring inhibition diameters. However, a otic concentration is not representative
regression line based on inhibition di- of a clinical context in which larger Figure 4 - Classification of a bacterium as sensitive, intermediate or resistant is defined by in vitro
criteria.
ameters is not a satisfactory method for populations of microorganisms are
determining the MIC. Several methods subject to fluctuating antibiotic con-
of analysis can be used to identify values centrations. • The site of infection can play a role. perfusion) are not taken into conside-
For example, an S result obtained in vit- ration. For example, an aminoglycoside
% of
ro overestimates antimicrobial activity can be effective in vitro on a certain
strains Bacteria = Escherichia coli in the central nervous system, the pros- strain (therefore declared sensitive), but
50 tate or mammary tissue. Conversely, ineffective in necrotic tissue or an abs-
an R result underestimates the activity cess4.
40 of local treatments (very high antibiotic • The patient’s clinical state: the risk of
concentration) or activity in urine for an treatment failure is higher in immuno-
30 antibiotic eliminated via the kidneys. compromised patients or those suffe-
• The possibilities of synergy between ring from severe chronic illness.
20 Critical clinical
Escherichia coli
“Cut off” two antibiotics are not identified by cul- Culture and sensitivity testing can also
values values S ≤ 0.5 mg/L ture and sensitivity testing. be used for epidemiological surveillance
10 R ≥ 4 mg/L • Local factors (e.g. pus, low partial oxy- of bacterial resistance and the fight
0
gen pressure, necrotic tissue, low tissue against nosocomial infections. n
0.002 0.004 0.008 0.016 0.032 0.063 0.125 0.25 0.5 1 2 4 8 MIC (mg/L)

Figure 3 - Critical values: the example of ciprofloxacin in humans.

314 315
Why is the result of sensitivity
testing not always reflected by
R.9

clinical efficacy?

n Antibiotic sensitivity testing rep- • underdosing (failure to op-


resents a single time point in vitro timize medication dosing reg-
measurement (snapshot) that does imens based on indication and pa-
not take into account patient and in- tient-specific characteristics) by the
RECOMMENDATIONS

RECOMMENDATIONS
fection-specific factors, nor technical clinician,
errors affecting the clinical predictive • underprescribing (omission of oth-
value. er potentially useful drugs) by the cli-
n Main factors that can be responsi- nician,
ble for the lack of correlation between • lack of compliance by the owner,
AST results and clinical efficacy are:
• unreliable clinical breakpoints (see
• factors influencing drug PK (e.g. in- recommendation R.8), Fungus infection combined with Microscopic view of Escherichia coli.
dividual factors, poor tissue diffusion, Staphylococcus on dog skin.
• errors or inaccuracies by the mi-
drug interactions),
crobiology laboratory.
• mixed infections, at the infection site, and drug interactions. by other factors occurring in the patient
Moreover, sensitivity tests represent a after a specimen is taken and submitted
In vitro sensitivity testing is a useful dia- proved in 3% and did not improve in 82% single time point measurement. As such, to the laboratory.
gnostic tool for predicting the activity of the patients treated with antibiotics to their predictive value may be influenced
of antimicrobial drugs in vivo. Various which the cultured strains were classi-
human studies have shown that there fied as resistant3. Clinical predictive value
is a clear negative correlation between
However, in vitro sensitivity tests are not The clinical predictive value of the re- sensitivity testing.
MICs and clinical outcomes of antibiotic
infallible and have shown little clinical sults of in vitro antimicrobial suscepti- The clinical predictive value of veterinary
treatment, i.e. the higher the MIC value
predictive value under specific situations bility testing was assessed by a prospec- sensitivity testing may be further affect-
of a drug, the lower the response rate
such as urinary tract infections, polymi- tive study for a cephalosporin widely ed by several sector-specific factors
to therapy1. The importance of sensiti-
crobial infections, outpatient infections used in human hospitals (cefotaxime). such as lack of:
vity testing for rational antibiotic therapy
treated with oral antibiotics, or infec- Infections associated with fully suscep- • harmonized laboratory procedures,
is exemplified by an old human study
showing that the clinical conditions im- tions treated with multiple antibiotics2. tible strains were not eradicated in 9%
• approved animal-specific and path-
of the patients. Even more surprisingly,
ogen-specific breakpoints for several
Variable correlation with clinical outcome infections associated with fully resist-
ant strains were eradicated in 50% of
veterinary drugs,
Several factors may be responsible underdosing or underprescribing by the patients2. Although similar studies • universal diagnostic licensing stand-
for the lack of correlation with clinical the clinician, lack of compliance by the have not been performed in veterinary ards for sensitivity testing, and
outcome including individual factors owner, unreliable clinical breakpoints, medicine, it is reasonable to expect that • targeted training programs for veter-
influencing drug pharmacokinetics or errors or inaccuracies by the laboratory, similar problems exist in veterinary inary laboratory and clinical personnel. n
response to therapy, strain virulence, drug inability to reach and be effective

316 317
What should be done if results of
R.10
sensitivity testing diverge from
clinical outcome? Underdosing
Underdosing should be avoided because as fluoroquinolones) as well as by fa-
it is a key cause of antibiotic treatment vouring development of resistance dur-
failure by reducing clinical efficacy ing treatment (see recommendation R.20).
n The veterinarian should carefully the clinical outcome is identified (especially of dose-dependent drugs such
consider any possible factors respon- (e.g. presence of biofilms, im-
sible for the lack of response to ther- plants and foreign material).
apy in patients infected with a strain
n Alternatively, therapy should be
Limited drug tissue penetration or reduced effi-
cacy at the infection site
RECOMMENDATIONS

RECOMMENDATIONS
that has been reported by the micro-
discontinued and another antibiotic
biology laboratory as susceptible (S)
should be chosen based on new sen- Limited drug penetration at the infection the lack of clinical efficacy may be due
(see recommendation R.9).
sitivity test results. site should be considered for specific to biofilms and/or implants and foreign
n Check first if the lack of clinical out- infections such as prostatitis or CNS material (presence of pus), inadequate
n On the contrary therapy should be
come may be due to failure of the pre- infections. For these infections it is rec- drainage or debridement and any other
continued if clinical improvement is
scribed drug to reach and be active at ommended to use a drug able to pene- factors affecting antibiotic activity at the
observed in patients infected with a
the infection site or for underdosing trate the organ-specific blood barrier, infection site (e.g. anaerobic conditions
strain that has been reported as re-
or lack of compliance by the owner such as a fluoroquinolone. interfere with the antimicrobial activity
sistant (R). Clinical outcomes should
(see recommendation R.9). of aminoglycosides).
always be prioritized over sensitivity For other infections, especially post-sur-
n Targeted action should be taken if results. gical and device-associated infections,
an infection-specific factor affecting
Underlying conditions
A number of factors may be responsible Specific underlying conditions in the antibiotic is used. In such cases a new
for the divergence between sensitivity patient may include any disorders that therapy with a bactericidal antibiotic
results and clinical outcome (see rec- compromise the immune system of the should be started and the underlying
ommendation R.9). The main factors to patient. Indeed, the immune system condition should be identified and man-
be considered for a negative response to plays a major role in curing the infec- aged, if possible.
therapy are: tion, especially when a bacteriostatic
• underdosing due to inaccurate weighing
of the patient or inadequate tablets for
correct dosing (large/small dogs),
Pitfalls in the laboratory diagnostic procedure
• limited drug tissue penetration or They may include collection of an inap- microbiology laboratory. If one of these
reduced efficacy at the infection site, propriate sample type, contamination situations is suspected, a new sample
of the sample at the time of collection, should be collected and submitted to
• specific underlying conditions in the
and errors in the performance or inter- the laboratory with a detailed descrip-
patient,
pretation of the sensitivity test by the tion of the case.
• pitfalls in the laboratory diagnostic
Figure 1 - Inadequacy of the prescribed drug to
procedure (from sampling to interpretation), reach the target organ, underdosing or lack of
• non-compliance by the owner. compliance are major causes of poor clinical
outcome.

318 319
R.10
What should be done if results of sensitivity
testing diverge from clinical outcome?

Non-compliance
Compliance by the owner is particu- tervals is essential to ensure drug
larly important for time-dependent levels above the MIC of the strain and
antibiotics such as the ß-lactams. Ad- ultimately to ensure clinical efficacy.
ministering ß-lactams at regular in-

What should be done in practice?


RECOMMENDATIONS

RECOMMENDATIONS
It may well happen that a patient re- strain reported as resistant is not the
sponds to therapy even if the infection primary cause of infection, or
has been attributed by the laboratory
to a resistant strain1. This apparently il-
• errors in the laboratory (e.g. reporting
of sensitivity results for bacterial con-
Broad-spectrum
logical outcome may be observed when
samples are submitted for culture at the
taminants, mistakes in the performance
of the test or application of inadequate
ANTIMICROBIALS,
time of initiating empirical therapy, and
can be consequent to:
breakpoints).
In all these cases, therapy should not be
combinations,
• self-limiting infections that would re-
solve without antibiotic therapy,
discontinued regardless of the sensitivity
results. n
de-escalation
• polymicrobial infections in which the

320 321
Does the use of a broad-spectrum antimicrobial
R.11
(or combination of antimicrobials) assist in doing
without bacterial sensitivity testing?
100% 100%
90 % 90 %
80% 80%
70% 70%
n The use of a broad-spectrum anti- n Initial treatment with broad-
60% 60%
biotic (or combination of antimicro- spectrum antibiotics should be 50% 50%
bials) as a first-line treatment does not short and reassessed on the basis 40% 40%
excuse the practitioner from looking of the bacteriological results (scaled 30% 30%
down to a narrower spectrum). Broad-
RECOMMENDATIONS

RECOMMENDATIONS
for the causal agent and site of infection. 20% 20%

n When choosing between antibiotics


spectrum antibiotics are more likely 10% 10%

of comparable efficacy, it is recom- to promote the selection and pro- 0% 0%


Broad-spectrum Narrow or Various Broad-spectrum Narrow or Various
mended to choose the one with the pagation of resistance in the host’s antibiotics Intermediate antibiotics Intermediate
spectrum antibiotics spectrum antibiotics
narrowest spectrum whenever pos- normal (commensal) flora.
sible. n For mild infections that do not re- 3-4G cephalosporins 1-2G cephalosporins Macrolides Nitroimidazole (metronidazole)

n In severe infections, septic shock


quire admission to hospital, empirical (Fluoro)quinolones Potentiade sulfonamides Lincosamides (Amino)penicillins
(clindamycin)
and nosocomial infections, bacterio- treatment can be carried out without Aminoglycosides Tetracyclines Various

logical analysis with culture and sen- bacteriological examination. However, Figure 1 - Most antibiotics prescribed by veterinarians are broad spectrum: >70% in dogs and
sitivity testing is essential when pre- in the event of failure or relapse, bac- >80% in cats. Data from an internet-based survey carried out in 2013 among 3,004 European veterinarians4.

scribing a broad-spectrum antibiotic teriological examination is needed.


as a first-line treatment. A sample n For infections occurring in a group However, there are several drawbacks Clinical and microbiological diagnosis
for bacteriological analysis should be of animals, early bacteriological exa- associated with their use: also becomes of secondary importance
taken before starting treatment. mination is recommended (see re- • There is no single broad-spectrum an- for the practitioner, as the treatment is
commendation R.29). tibiotic (or combination) that is effective supposed to act on all the pathogenic
against all bacteria2. bacteria potentially involved. Thomson9,
Narrow-spectrum antibiotics (penicillin G, antibiotics (tetracyclines, chloramphenicol, • Their broad spectrum is reassuring 2009 and Escher5, 2011 report that the
metronidazole, colistin) and intermediate 3rd generation cephalosporins, fluoro- and encourages a blind, ‘‘just in case’’ choice of the antimicrobial treatment
antibiotics (aminoglycosides, macrolides, quinolones) act on both Gram-positive treatment without actually confirming is supported by culture and sensitivity
lincosamides) mainly act on one cate- and Gram-negative bacteria, aerobic and the presence of an infection (non-rea- testing in less than 5% in dogs and cats.
gory of bacteria (Gram-positive or ne- sometimes even anaerobic bacteria soned prescription), instead of rational In Europe, sensitivity testing is always
gative, anaerobic or aerobic) (see Table (see Table 1 of recommendation R.13). prescription considering likely bacte- performed (when feasible) by only 3.4%
1 of recommendation R.13). It is recom- These agents are widely used as first- ria and whether a narrow spectrum of companion animal practitioners3.
mended to choose the antibiotic with the line treatment in both dogs and cats drug could be efficacious (empirical or
(Figure 1), with differences according probabilistic treatment). For example, Broad-spectrum antibiotics exert a se-
narrowest spectrum whenever possible. lective pressure on a greater number of
to the country3,4. Perceived higher ef- only 5% of urine cultures are positive in
Broad-spectrum antibiotics (ampicillin, ficacy and uncertainty of diagnosis are cats with urological signs1. In the majority of microorganisms than narrow spectrum
amoxicillin ± clavulanate, 1st genera- the most frequent reasons mentioned cases, no clinical hypotheses are made antibiotics, and are consequently more
tion cephalosporins, trimethoprim-sul- by veterinarians for the selection of as to whether there actually is an infection susceptible to promote the selection
fonamides) and very broad-spectrum broad-spectrum antimicrobials8. present or the nature of the causal and propagation of resistance in the host’s
agent (or even the site of the infection). normal (commensal) flora. Moreover,

322 323
R.11 Does the use of a broad-spectrum antimicrobial
(or combination of antimicrobials) assist in doing
without bacterial sensitivity testing?

a massive alteration of digestive flora with possible de-escalation of therapy


will have a negative impact on its after 48-72 hours based on culture and
barrier function, which will promote the sensitivity (Figure 2). This strategy, while
Clinical signs, severity,
colonization of the digestive tract by path- ensuring a high likelihood of adequate
local prevalence etc.
ogenic bacteria. initial coverage, avoids the long-term
The need to carry out bacteriological use of unnecessary antibiotics, thereby
minimizing resistance concerns6. The
analysis with culture and sensitivity
use of narrower spectrum antibiotics
depends on the clinical condition of the Suspicion of pathogen
limits the impact of antibiotic therapy
animal. The approach can be summa-
on non-targeted bacteria in normal flora.
RECOMMENDATIONS

RECOMMENDATIONS
rized as follows10:
De-escalation may also include dis-
• For serious infections (e.g. pyothorax, continuation of empirical antimicrobial
osteomyelitis, pyelonephritis, septic shock Sample for culture & AST
therapy based on clinical criteria and and for cytology
and nosocomial infections), the sample negative culture results.
for bacteriological examination must be • For mild infections that do not require
taken before starting treatment. In such admission to hospital, empirical (pro-
conditions, the antimicrobial treatment babilistic) treatment can be carried out Culture & AST: Empirical (probabilistic)
should be initiated as soon as possible results after 48 to 72 hours antibiotic therapy < 3-4 days
without culture. In the event of failure or
after the onset of sepsis, i.e. generally a relapse, bacterial sensitivity testing is
before the causative pathogen is known. requested.
As therapy is to be initiated empirically • For every infection occurring in a Reassessement of initial
the antimicrobial spectrum of the agent group of animals, a bacteriological exa- treatment (& de-escalation)
should be broad enough to cover the po- mination is recommended, regardless
tential causative microorganisms. of the seriousness of the clinical signs
Antimicrobial management therefore and the spectrum of action of the an-
incorporates early implementation of tibiotic used in the first-line treatment Final treatment
broad-spectrum empirical coverage (see recommendation R.29). n

Regular reassessment until


the end of treatment

Figure 2 - Strategy for prescribing antibiotics to an animal with a serious infection.

Broad spectrum antibiotics act on both pathogenic bacteria and digestive flora indiscriminately.

324 325
R.12
What are the rules of antibiotic
combinations?*
SYNERGY ANTAGONISM
10 Control a. An 10
antibiotic combination (A+B)

Log number

Log number
of bacteria

of bacteria
8 B is said 8synergetic when its effect is
n Antibiotic combinations are usually • caused by a large quantity of 6 greater6 than the sum of the effects
pointless and should be avoided. bacterial inoculum, 4 A of two antibiotics
4 (A,B) taken sepa-
2 retely compared
2 to control.
• serious or potentially lethal, A+B
n Monotherapy should be the first
choice in the majority of infections. It • in immunodepressed dogs and Time (h) Time (h
RECOMMENDATIONS

RECOMMENDATIONS
must be used when: cats.
• the bacterial agent is identified and SYNERGY
n A probabilistic treatment is not a ANTAGONISM
sensitive to the antibiotic, blind treatment.
10 A combination can- Control 10 Control
b. When the effect of a combination

Log number

Log number
of bacteria

of bacteria
• the antibiotic prescribed as a not be justified
8 on the basis of broad- B 8 B
A+B is lower than the sum of the effects
probabilistic treatment is generally 6
ening the antimicrobial spectrum. 6
of each antibiotic taken separately,
4 A 4
recognized as being effective for the n In theory,
2 the main objectives of 2
this is called antagonism.
A+B A
infection involved, prescribing an antibiotic combination
Time (h) Time (h)
• the infection is not very serious. are the following:
n In spite of the absence of data, using • to broaden the therapeutic spec- Figure 1 - Synergetic or antagonistic effect of an antibiotic combination.
a combination is possible in specific trum,
clinical circumstances, namely first- • to obtain a synergy,
line emergency treatment of infections • to decrease the appearance of re- unit, the percentage of sensitive bac- large quantities of bacterial inoculum,
that are: sistance. teria isolated was significantly identical potentially lethal infections or infections
• polymicrobial, for gentamicin (74%) and for an enro- in immunodepressed subjects whose
floxacin-ampicillin combination (71%). aetiology is uncertain, there is a con-
The probabilistic treatment chosen by sensus in veterinary literature on the
Broadening the spectrum the emergency physician was effica- subject which allows the possible use of
Broadening the spectrum is certainly On the contra­ry, it is a prescription that cious in 75% of cases2. A consensus an antibiotic combination.
the easiest objective to achieve through has to be well-thought, considering all of the American College of Veterinary However, broadening of the spectrum is
a combination, in particularly in cases of available information to make the best Internal Medicine recommends us- no longer legitimate once the bacterio-
polymicrobial infections with mixed aero- possible choice. ing narrow spectrum antibiotherapy in logical diagnosis has been carried out
anaerobic flora. Prescribing a combination with the the majority of infections8. In cases of and a targeted treatment can be started.
During probabilistic treatment, however, sole aim of broadening the antibio- polymicrobial infections, multiple sites,
the prescription of an antibiotic com- therapy spectrum without any other
bination is very frequently not justified. reason generally indicates a lack of Combination synergy
So-called probabilistic antibiotherapy ability in diagnosing and a lack of
must correspond to a treatment that is knowledge in the field of infectiology. Synergy (or antagonism) is defined as (or lower) than the sum of the actions
recognized as being regularly effective For example, in a study carried out on being a positive (or negative) interaction of each antibiotic prescribed separately
in the given situation. 74 dogs hospitalized in an intensive care between two antibiotics, leading to a (Figure 1)6. The aim is also to have a bac-
joint antibacterial action which is greater tericidal action, which is faster if possible.
* Not including trimethoprim sulfonamide and amoxicillin+clavulanate combinations.

326 327
What are the rules of antibiotic
R.12
combinations?*

Traditional rules of combination (Jawetz In fact, each antibiotic’s mode of action Apart from these examples, no dif- therapy. The risk of adverse effects,
laws), for example the antagonism between is influenced by pharmacokinetic and ference in terms of superinfection in particular nephrotoxicity, is on the
bacteriostatic and bactericidal drugs, pharmacodynamic parameters. These and resistance development has been other hand greater when using a bi-
are old concepts with many exceptions. two factors can be modified by in vivo observed between the bi- and mono- therapy1,3,5,7,9,10,11. n
The most common strategy is to combine interactions when the two agents are
two agents (e.g. penicillins, cephalo- administered together.
sporins, aminoglycosides, fluoroquinolo-
nes). The synergy mechanisms are:
• easier penetration of an antibiotic (e.g.
RECOMMENDATIONS

RECOMMENDATIONS
aminoglycoside) into the bacteria due to
another antibiotic (ß-lactams),
• sequential inhibition of the same met-
abolic pathway (e.g. trimethoprim and
sulfonamides),
• inhibition of bacterial cell wall synthe-
sis (vancomycin and ß-lactams),
• inhibition of ß-lactamases (amoxicillin
and clavulanate).
Bacteriological tests to determine the
effects of a combination are often la-
borious and not available. The synergy
(or antagonism) observed in vitro cannot A combination cannot be justified on the basis
necessarily be extrapolated to in vivo of broadening the antimicrobial spectrum.
conditions.

Decrease in the appearance of resistance


The effect of combinations on the ap- drug-resistant strains appearing. When
pearance of resistance is debatable. In antibiotics are combined to this end, the
fact, combinations accentuate selective antibiotics chosen should have different
pressure and therefore the risk of multi- modes of action.

Clinical interest
The clinical advantage of an antibiotic shown by several meta-analyses that
combination over a monotherapy re- the ß-lactam/aminoglycoside combina-
mains to be demonstrated when treat- tion is superior to a monotherapy with
ing dogs and cats. ß-lactams in cases of infectious endo-
In human medicine, it has certainly been carditis in young neutropenic patients.
* Not including trimethoprim sulfonamide and amoxicillin+clavulanate combinations.

328 329
R.13
Which antimicrobials have
a narrow spectrum? spectrum agents some antimicrobials of pathogens, while drugs with broad-
are ‘‘broader’’ than others (e.g. macro- spectrum activity are effective against
lides vs. metronidazole), while in the a wide variety of pathogens. In a giv-
broad-spectrum category some antibio- en class of antibacterial drugs, such a
tics are ‘‘narrower’’ than the very broad classification still remains confusing.
n The ‘‘broad vs. narrow spectrum’’ n Appropriate use of narrow-
ones (e.g. tetracyclines vs. 3rd genera- For example, amoxicillin is considered
classification can be misleading for spectrum antibiotics implies a
tion fluoroquinolones). a broad-spectrum penicillin, suggest-
the practitioner as its definition is not targeted antimicrobial therapy, en-
clear. suring a high likelihood of cure while More generally, drugs with narrow- ing that it is effective against a wide
minimizing resistance concerns and spectrum activity are considered as variety of pathogens. Although amoxi-
RECOMMENDATIONS

RECOMMENDATIONS
n Generally, drugs with narrow-spec-
is based on identification of the cau- agents effective against a limited variety cillin has indeed a wider activity against
trum activity are considered effective
against a limited variety of pathogens sal pathogen, bacterial sensitivity
while drugs with broad-spectrum ac- testing and knowledge of the PK/PD
tivity are effective against a wide va- characteristics of the agent. Table 1 - Antibacterial activity of selected antibiotics.

riety of pathogens. n Whenever possible, a narrow-spec- Aerobic Anaerobic


n Narrow-spectrum antibacterial agents
trum antibiotic should always be pre- bacteria bacteria
include penicillin G, nitroimidazoles ferred over a broad-spectrum anti-
Spectrum Gram + Gram - Gram + Gram - Examples
(metronidazole) and colistin. biotic.
Very broad Chloramphenicol
Very broad 3rd generation fluoroquinolones
The use of the ‘‘broad vs. narrow spec- initially given to an antibiotic by compar-
trum’’ classification is increasingly un- ison to other antimicrobial agents. Very broad 3rd and 4th generation cephalosporins
common in most textbooks in human Later, broad and narrow spectrum be- Very broad Tetracyclines
and veterinary medicine, as its interpre- came independent characteristics of the
tation may be misleading for the prac- Broad Ampicillin, amoxicillin (± clavulanate)
antimicrobial agent, mainly based on
titioner. its specific activity against a spectrum Broad 1st generation cephalosporins
The expression ‘‘broad-spectrum an- of microorganisms, according to their
tibiotic’’ was first mentioned in the lit- Broad Trimethoprim - sulfonamides
Gram-stain. Narrow-spectrum antibi-
erature in the 1950s for comparison of otics are defined as agents only active Intermediate Aminoglycosides
the spectrum of chloramphenicol and against Gram-positive or Gram-neg-
Intermediate Macrolides, lincosamides
tetracyclines to the narrow spectrum of ative bacteria, whilst broad-spectrum
penicillin G and streptomycin1. Parent antibiotics are active against both Narrow Penicillins G (or M)
molecules were also chemically modi- Gram-positive and Gram-negative bac- Narrow Nitroimidazoles (metronidazole)
fied to extend the range of antimicrobial teria. However, this classification is
activity (e.g. amoxicillin is an extend- not always straightforward, as some Narrow Colistin
ed-spectrum antibiotic compared to agents may be primarily active against
its parent molecule penicillin G, which Gram-positive bacteria but will also in- Excellent activity Limited activity
has a narrow spectrum). Therefore, the hibit the growth of certain Gram-nega-
Moderate activity No or negligible activity
terms broad or narrow spectrum were tive agents2 (Table 1). Among the narrow

330 331
Which antimicrobials have
R.13
a narrow spectrum?

Gram-negative bacteria, it is slightly spectrum antimicrobial agents are less


less active against Gram-positive and susceptible to promote the selection
anaerobic bacteria than penicillin G. The and propagation of resistance in the
emergence of many resistant strains of commensal flora. Their use however
Gram-negative bacteria reduces the requires an appropriate identification
spectrum of clinical use for amoxicillin. of the causal pathogen, interpreta-
Today, narrow-spectrum agents require tion of bacterial sensitivity testing and
targeted antimicrobial therapy, en- knowledge of the PK/PD characteristics
suring a high likelihood of cure while (e.g. distribution to the infection site) of
RECOMMENDATIONS

RECOMMENDATIONS
minimizing resistance concerns. Narrow- the selected narrow-spectrum agent. n

The use of narrow-spectrum antibiotics is recommended but it requires identification of the causal
pathogen and interpretation of antibiotic sensitivity testing.

332 333
R.14
Which therapeutic approach is
recommended while awaiting results?
While awaiting results, perform risk assessment
for the decision on treatment:
• Management of underlying disease
n The results of common bacterial is only justified in emergency • Supportive treatment
analyses of aerobic microorganisms cases, in life-threatening condi-
are generally known after 48-72 hours. tions or in non-emergency situations
It takes longer for anaerobic bacteria where delay would compromise the
RECOMMENDATIONS

RECOMMENDATIONS
or if the bacteria are less viable (e.g. clinical outcome. Patients with (potentially) Patients with
sample taken from an animal already life-threatening conditions other conditions
n 48 to 72 hours after the start of
taking antibiotics, see recommenda-
treatment, it is reassessed on the
tion R.5).
basis of the clinical improvement
n If bacterial infection is clinically observed and the results of analysis.
suspected, empirical antibiotic therapy Empirical antimicrobial therapy Treatment can be delayed.
should be initiated (’’hit hard and hit fast’’) Wait for results to tailor the
The antimicrobial drug is selected based antibiotic therapy
Therapeutic approach while awaiting results on cytology, the site of infection,
the immune status, the risk factors
to the individual patient

For an accurate diagnosis and an ap- patients should be risk-assessed for for antibiotic resistance and the
propriate treatment, clinicians should treatment decisions. There are two op- potential resistance patterns.
perform cytology and ensure that speci- tions (Figure 1):
mens for culture and antibiotic suscep- • In life-threatening (or potentially life-
tibility testing are properly sampled and threatening) infections (e.g. septic shock),
promptly submitted to the laboratory. empirical antimicrobial therapy must be When susceptibility results become available:
Premature initiation of antimicrobial initiated as quickly as possible (‘‘hit hard
therapy can suppress bacterial growth and hit fast’’) to limit the development ■ Consider de-escalation Prefer first-line antibiotics
and preclude the opportunity to esta- of infection and its complications. Other ■ Adjust treatment if needed whenever possible
blish a microbiological diagnosis. The potential testing (e.g. imaging) should
time required for results of bacterial not delay antimicrobial therapy. Figure 1 - Risk-assessment for decision on treatment while awaiting laboratory results.
culture and sensitivity testing depends • For other infections, it is recom-
on the laboratory technique used. It mended to wait for the microbiological
is generally 48-72 hours for aerobic diagnosis before starting antimicrobial In potentially lethal infections, empirical different antibiotic classes for the given
bacteria (often longer for anaerobic bac- treatment. In non-emergency settings, treatment implies that the antibacterial infection3.
teria), but may be prolonged according the practitioner should take the time agent should be selected appropriate- Although the microbiological diagnosis
to the viability of the pathogens (pre- to tailor therapy to the individual pa- ly according to the site of infection, the is ideally based on laboratory data,
vious antimicrobial treatment before tient based on the best clinical judg- patient’s immune status (e.g. geriatric frequently the “most likely” pathogen
sampling can delay bacterial growth) ment and laboratory information. Such or cancer patients), the risk factors for cause can be inferred from the clinical
and their natural growth rate (from 24 a short delay of treatment is not harm- antimicrobial resistance (e.g. prior hos- presentation and the site of infection
hours to several days). ful and helps in reducing the amount of pitalization, recent antimicrobial use), based on epidemiological considerations,
While awaiting results, small animal unnecessary or ineffective antibiotics. and the potential resistance patterns to and from cytology results. For example,

334 335
Which therapeutic approach is
R.14
recommended while awaiting results?

about 70% of isolates in complicat- with the intent to cover multiple possible
ed urinary tract infections in dogs are pathogens commonly associated with
Gram-negative. E. coli is isolated in the infectious disease. This therapeu-
about 60% of cases4. Immune suppres- tic approach improves the likelihood of
sion and co-morbidities should be also appropriate antimicrobial coverage while
considered as they may affect the re- waiting for the laboratory results. Anti-
sponse to the antimicrobial treatment, microbial treatment will be adjusted
e.g. 35% and 30% of dogs with com- when the pathogen has been identi-
plicated urinary tract infection have, fied and its susceptibility evaluated. To
RECOMMENDATIONS

RECOMMENDATIONS
respectively, immune suppression and reduce the risk for development of an-
renal disease4. timicrobial resistance, a strict policy of
For these reasons, broad-spectrum therapy de-escalation based on antimi-
antibiotics are recommended for em- crobial susceptibility testing should be
pirical treatment in critically ill patients followed (see recommendation R.11).

Antibiotic dosing during critical illness


Dosing of antimicrobials during critical rameters in such conditions. However,
illness is generally problematic as an- from the available data in human pa-
timicrobial concentrations are subject tients, underdosing appears much more For non-emergency situations and non-life-threatening situations, it is recommended to wait for
to alterations and may fail to reach ap- frequent than overdosing2. An intrave- the microbiological results prior to initiating antibiotic therapy.
propriate therapeutic levels. Five main nous loading dose is generally recom-
issues can be detected in critically ill mended to achieve appropriate concen-
patients regarding altered pharmaco- trations more rapidly3. In emergency and
kinetics (PK): increased volume of dis- critical care clinics, it is recommended
tribution, altered protein binding, aug- to establish and use a specific empirical
mented renal clearance, impaired re- antimicrobial protocol for the treatment
nal clearance and hepatic dysfunction. of life-threatening infections to improve
There is no easy way to predict PK pa- time to antimicrobial administration1. n

336 337
RECOMMENDATIONS

RECOMMENDATIONS
Long-acting
antimicrobials

338 339
R.15
What is the benefit/risk ratio of
(very) long-acting antimicrobials?
Plasma concentration

Antibiotic with a long half-life

n Time-dependent drugs (e.g. ß-lac- properly administered (especially Antibiotic with a short half-life
tams) are slowly bactericidal. Serum in uncooperative cats) and so avoids
concentrations therefore should ex- the risks of owner non-compliance.
ceed the minimum inhibitory concen- n However, a very slow decrease in
RECOMMENDATIONS

RECOMMENDATIONS
tration (MIC) for as long as possible drug concentration exposes these MIC
during the dosing interval, either by bacteria to sub-inhibitory concentra-
continuous infusion or by frequent tions (lower than the MIC) for a longer Increased risk of
dosing. period than with a short elimination resistance selection t

n Time-dependent antimicrobials with half-life antibiotic. Consequently, the Figure 1 - Comparison of the plasma vs. time concentrations of antibiotics with a long or a short
risk of resistant mutant selection and elimination half-life in relation to the MIC and to the risk of resistance selection.
a long elimination half-life (t1/2) (e.g.
cefovecin) have a prolonged treatment adverse effects on commensal bacte-
efficacy following a single adminis- ria may be greater.
antibiotic (Figure 1), and consequently both Gram-positive and Gram-negative
tration. Subsequent administration, n Before administering long-acting the risk of resistant mutant selection is (aerobic and anaerobic) pathogens as-
if any, should be carried out before or antimicrobials, the risks should be greater. Once the cure has been achieved sociated with skin, urinary tract and pe-
at the time when concentration drops discussed with the owner and the and the pathogens have been killed, it is riodontal infections in dogs and cats12.
below the MIC. The immediate ben- benefits to the patient should clearly important to consider that antibiotics do Clinical efficacy and safety of cefovecin
efits of such a treatment are that it out-weigh the risks, especially when not only target pathogenic bacteria but in cats and dogs was demonstrated in
ensures the full course of therapy is it is a critically important antibiotic. can also have damaging effects on the urinary tract infections8,9, abscesses
ecology of commensal species (skin, and infected wounds10,11,15,16,, and more
gut...). This exposure can lead to de- recently in canine Lyme disease18.
Time-dependent drugs, like ß-lactams, Optimal antimicrobial therapy not only creased susceptibility and the develop- However, in cats with clinical signs of
are slowly bactericidal. The serum involves maximizing therapeutic out- ment of multidrug-resistant bacteria5. upper respiratory tract disease, a single
concentration therefore should exceed come but also minimizing the risk of SC injection of cefovecin appears less
A well–documented example of a
the minimum inhibitory concentration emerging resistance during treatment. effective than repeated oral adminis-
long-acting antimicrobial widely used
(MIC) for as long as possible during the Discontinuation of the long-acting anti- trations of amoxicillin + clavulanate or
in small animal medicine is cefovecin, a
dosing interval, either by continuous in- biotic administration will lead to a pro- doxycycline4.
semi-synthetic 3rd generation long-act-
fusion or by frequent dosing. Time-de- gressive decrease in its concentration. If
ing cephalosporin authorized for use by Cefovecin is rapidly and completely ab-
pendent antimicrobials with a long pathogenic bacteria persist, re-growth
subcutaneous administration in dogs sorbed and fully bioavailable following
elimination half-life (t1/2) have the ad- of bacteria will start again once serum
and cats. However cefovecin is a critical- SC administration13,14. Most of the dose
vantage of prolonged treatment efficacy drug levels fall below the MIC value. A
ly important antibiotic so should be used is excreted unchanged in the urine. The
following a single administration. The very slow decrease exposes these bac-
with care under very specific conditions exceptionally long elimination half-life
subsequent antimicrobial administra- teria to sub-inhibitory concentrations
(see recommendations R.16 and R.17). of cefovecin (5.5 and 6.9 days, respec-
tion should be performed when concen- (lower than the MIC) for a longer period
trations approach the MIC. than with a short elimination half-life Cefovecin is a very broad-spectrum an- tively, in dogs and cats), partly explained
timicrobial, with in vitro activity against by high protein binding (95-100%), allows

340 341
What is the benefit/risk ratio of
R.15
(very) long-acting antimicrobials?

treatment with a single injection every As previously explained, one of the major
14 days13,14. Therefore, administration risks of such long-acting antimicrobial
of cefovecin by the practitioner ensures therapy is that antimicrobial resistance
that the full course of therapy is pro- and perturbation of the commensal BENEFITS RISKS
perly administered and that the patient flora may occur. ß-lactam resistance
(especially uncooperative cats) receives was reported to be more common in
a full dose. Rather than covering for a faecal E. coli after cefovecin treatment
hypothetical risk of owner non-com- in healthy dogs3. Further investigations
pliance, the vet should restrict these are needed to determine the potential
RECOMMENDATIONS

RECOMMENDATIONS
treatments to animals where there is adverse effects of other antimicrobials
an acknowledged problem with com- on the gut microflora and resistance
pliance: appetent tablets or solutions emergence in clinically ill patients.
that can be put in the food will solve the Owner and patient
It can be currently recommended that, compliance
problem in many cases. This distinct when prescribing long-acting antimi- Long lasting disturbance
advantage probably explains the wide- crobials, the benefits to the patient if adverse effects
spread and frequent use of cefovecin in should clearly outweigh the risks (Fig- Convenience
small animals, especially in cats, up to 17% ure 2). n Perturbation
of non-topical antimicrobial prescription2,6,7. of commensal flora

Resistance emergence,
public health issue

Figure 2 - Risk-benefit balance of long-acting antimicrobials.


When prescribing a long-acting antimicrobial therapy, the practitioner should perform an indi-
vidual benefit/risk evaluation based on the drug’s potential benefits outweighing the potential
risks.

Prolonged-action antibiotics have an increased risk of resistance selection.

342 343
RECOMMENDATIONS

RECOMMENDATIONS
Critically important
antibiotics

344 345
Under which circumstances may
R.16
3rd and 4th generation cephalosporins
and fluoroquinolones be prescribed? 1st and 2nd generation cephalosporins). are well absorbed and have a wide
tissue diffusion. Cephalosporins are
Cephalosporins are usually highly resist- among the safest antimicrobial drugs10.
ant to ß-lactamase enzymes, but path-
ogens are increasingly developing re- For all these reasons, fluoroquinolones
n 3rd generation cephalosporins (e.g. requiring their pharmacokinetic
sistance through production of extended and 3rd and 4th generation cephalospor-
cefovecin) and 3rd and 4th generation specific factors (e.g. prostatitis,
spectrum ß-lactamases that target 3rd ins have become increasingly popular
fluoroquinolones (e.g. enrofloxacin, rhinitis).
and 4th generation drugs. Fourth gen- classes of antibiotics for prescription for
marbofloxacin, pradofloxacin) must n The recommendations to be fol- eration cephalosporins may be effec- a variety of infections in both human and
RECOMMENDATIONS

RECOMMENDATIONS
not be prescribed as a first-line treat- lowed are: tive against anaerobic bacteria. Third veterinary medicine.
ment to avoid the emergence of re- • carry out a bacteriological exami- and fourth generation cephalosporins
sistance which is potentially danger- nation before starting treatment,
ous for animal and human health.
• reduce the risk for development of
n These antibiotics are only recom-
antimicrobial resistance by “de-esca- What evidence is there for their over-use and
mended if culture and sensitivity re-
sults demonstrate the need for such a
lating” (down-staging) if antimicro-
bial susceptibility testing shows that
what problems does that cause?
prescription. a narrower spectrum antibiotic can Conversely, this widespread use has
n However, these antibiotics can be be used, led to more prevalent resistance to
indicated as first-line empirical treat- • use the recommended dose and avoid these antimicrobial agents. Increasing
ment for life-threatening infections prolonged antimicrobial treatment. resistance trends for cefovecin and en-
(e.g. sepsis) or specific conditions rofloxacin were reported in clinical iso-
lates of Staphylococcus intermedius
group (including Staphylococcus pseu-
Why are 3rd generation cephalosporins and 3rd dintermedius) isolated from UK dogs
and 4th generation fluoroquinolones so popular? and cats between January 2002 and De-
cember 20121. In the US, a substantial
Fluoroquinolones offer many advan- tions are also achieved in prostatic fluid, rate of resistance (20%) to enrofloxacin
tages for the treatment of infectious dis- bone and cerebrospinal fluid. Fluoro- in pathogenic E. coli isolates3 and an More than any other antibiotics, prescription
eases. They have good to excellent in vitro quinolones are considered as relatively increased frequency of S. intermedius of 3rd generation cephalosporins and quino-
activity against a wide range of aer- safe antimicrobial agents, although ar- isolates with resistance to fluoroquino- lones must follow prudent use guidelines.
obic Gram-positive and Gram-negative thropathies in juvenile dogs and retinal lones7 have been reported.
bacteria, as well as Mycoplasma spp. degeneration with high doses of enro-
All fluoroquinolones (except pradofloxa- floxacin in cats have been reported12.
cin) approved in veterinary medicine are ‘‘Critically important antimicrobials’’: what does
considered ineffective against the strict Third and fourth-generation cepha-
anaerobes. They have high oral bioavai- losporins are also characterized by a it mean?
lability and an extensive tissue distribu- very broad spectrum of activity against Third and fourth generation cephalos- Health Organisation16, as they meet the
tion in dogs and cats. Particularly high Gram-negative and Gram-positive bac- porins and fluoroquinolones are classi- two criteria required for this categoriza-
concentrations are found in the kidneys teria (though activity on Gram-positive fied among the most critically important tion (Table 1). Use of antimicrobials that
and liver, while therapeutic concentra- bacteria may not always be as good as antimicrobials for humans by the World are critically important for human health

346 347
R.16 Under which circumstances may 3rd and 4th
generation cephalosporins and fluoroquinolones
be prescribed?

in companion animals is an additional Veterinary Use (CVMP)4 is that ‘‘The use


risk factor for the emergence and trans- in companion animals of substances
Selection of fluoroquinolones and Should not be employed in patients that are:
mission of antimicrobial resistance. regarded as critically important anti- 3rd or 4th generation cephalosporins - likely to recover without treatment,
Although this risk has been observed microbials (CIA) for human medicine - likely to be managed throught treatment with primary
for 15 years, above all in livestock, it should be carefully assessed considering use drugs,
- unlikely to survive regardless of the therapeutic regimen.
should not be underestimated in dogs the importance of those substances
Should be reserved when culture and sensitivity results
and cats. An important aspect related to for public health, and possible limi- indicate that primary use drugs are not appropriate.
antimicrobial resistance in companion tations on the use of human last re-
May be prescribed in life-threatening conditions as empirical
animals is their close contact with hu- sort (life-saving) antimicrobials for antimicrobial treatment. De-escalation should be considered
RECOMMENDATIONS

RECOMMENDATIONS
mans potentially increasing the risk of treatment of companion animals should once culture and susceptibility testing results are available.
interspecies transmission of (multidrug) be considered.’’ To avoid regulatory re-
resistant bacteria, as pets can act as strictions or prohibition of use of such Selection of the dose Use the label dose and dosing interval, but be aware that
reservoirs8,14. MDR bacteria in dogs and antimicrobials in the future, responsi- underdosing may occur in critically ill patients.
cats (MRSP, MRSA and ESBL-producing ble and prudent use (“the precautionary
Selection of the treatment duration Avoid prolonged treatment.
E. coli) are resistant to 3rd generation ceph- principle”) of 3rd and 4th generation ceph-
alosporins and therefore are likely to alosporins and fluoroquinolones in small Figure 1 - Prudent use of fluoroquinolones, 3rd and 4th generation cephalosporins.
be selected by the use of these drugs. animals should therefore be promoted Prudent use means the optimal selection of drug, dose and duration of antimicrobial therapy
The current recommendation of the and practised by the veterinary profes- along with reduction of inappropriate and excessive use, as a means of slowing the emergence
of antimicrobial resistance13.
Committee for Medicinal Products for sion14.

How can these antimicrobials be used ‘‘prudently’’? in patients that are unlikely to survive
regardless of the therapeutic regimen.
Prudent use means the optimal selection lones, which are generally assigned to In some life-threatening diseases (e.g.
of drug, dose and duration of antimi- the secondary use category9. Limited sepsis, patients with immune suppres-
crobial therapy along with reduction of use of fluoroquinolones and 3rd and 4th sion and serious comorbidities) or in
inappropriate and excessive use, as a generation cephalosporins is now specific conditions requiring specific
means of slowing the emergence of an- widely accepted. These antimicrobials pharmacokinetic factors (e.g. prostatitis,
timicrobial resistance13 (Figure 1). The should be reserved for use in speci- rhinitis), fluoroquinolones and 3rd and
current knowledge relating to prudent fic conditions requiring their specific 4th generation cephalosporins may be
use of antibiotics is limited and direct pharmacokinetic factors (e.g. prosta- initially prescribed as empirical antimi-
evidence of the benefit is often lacking. titis, rhinitis), when culture and sen- crobial treatment. De-escalation should
Some recommendations however have sitivity results indicate that primary be considered whenever possible, as
been endorsed by national veterina- use drugs are not appropriate9,13 or more targeted treatment can often be
ry organizations13. It is essential to re- when compliance cannot be achieved. achieved once culture and susceptibility
member that 1st line (or primary use) As written in the 2005 ACVIM consen- testing results are available14. Fluoro-
antimicrobial agents are often useful sus statement9, these drugs should not quinolones and 3rd and 4th generation ce-
First-line antimicrobial agents are as effec-
for the treatment of most bacterial in- be employed in patients that are likely phalosporins may be inefficient in such tive as 3rd and 4th generation cephalosporins
fections. In most circumstances, they to recover without treatment, in patients clinical settings. A recent study in dogs and fluoroquinolones in most circumstances.
are just as effective as 3rd and 4th gene- that are as likely to be managed through with abdominal sepsis5 demonstrated Their use should be preferred in 1st intention.
ration cephalosporins and fluoroquino- treatment with primary use drugs, or that empirical antimicrobial treatments

348 349
R.16 Under which circumstances may 3rd and 4th
generation cephalosporins and fluoroquinolones
be prescribed?

were inappropriate (based on the re- used inappropriate antimicrobials being


sistance pattern of bacteria according amoxicillin + clavulanate and cefuroxime, Table 1 - Criteria for categorization of cephalosporins (3rd and 4th generation) and fluoroquinolones
as critically important antimicrobials in human medicine.
to culture and sensitivity results) in but also a fluoroquinolone.
47.4% of cases, the most commonly Antimicrobial class Criterion 1 Criterion 2
Limited therapy for acute
How does use of a licensed veterinary 3rd gene- bacterial meningitis and
disease due to Salmonella
ration cephalosporin or fluoroquinolones fit into in children.
Disease may result from
this?
RECOMMENDATIONS

RECOMMENDATIONS
Limited therapy for infections
transmission of
due to multidrug resistant
The label dose and dosing intervals of considered to be one of the strategies Enterobacteriaceae
Cephalosporins Enterobacteriaceae, which
including E. coli and
fluoroquinolones and 3rd and 4th gener- to reduce the increasing antibiotic re- (3rd and 4th generation) are increasing in incidence
Salmonella spp. from
ation cephalosporins are generally con- sistance by decreasing the exposure of worldwide.
non-human sources.
sistent with current guidelines about commensal bacterial populations to anti- Additionally, 4th generation
antimicrobial use. However, these dos- microbial drugs14. In humans, 7 days of cephalosporins provide
es may be inappropriate during crit- treatment for acute pyelonephritis is for limited therapy for empirical
ical illness as drug metabolism and example equivalent to longer treatment treatment of neutropenic
excretion may be altered. In critically ill in terms of clinical failure and microbi- patients with persistent fever.
human patients, underdosing appears to ological failure, including in bacteraemic
Disease may result
be much more frequent than overdosing, patients6,11. Limited data are available in
Limited therapy for from transmission of
leading to poor clinical outcomes and re- veterinary medicine. In dogs with urinary
Campylobacter spp., Campylobacter spp.
sistance emergence2. Currently, in small tract infections, the microbiological and
Fluoroquinolones invasive disease due to and Enterobacteriaceae
animal medicine, the effect of critical clinical cure rates with a high dose (18- Salmonella spp. and MDR including E. coli and
illness on efficient dosing has not been 20 mg/kg PO q24h) of enrofloxacin for Shigella spp. infections. Salmonella spp. from
evaluated. Prolonged treatment with 3 days were 77.1% and 88.6%, respec- non-human sources.
fluoroquinolones or 3rd and 4th genera- tively, and were not inferior to those fol-
Criterion 1: An antimicrobial that is the sole agent or one of limited available therapy, to treat
tion cephalosporins should be avoided, lowing a 14-day treatment regimen with serious human disease.
as shortening the duration of therapy is amoxicillin + clavulanate15. n Criterion 2: An antimicrobial agent that is used to treat diseases caused by either: (1) organisms
that may be transmitted to humans from non-human sources or, (2) human diseases caused by
organisms that may acquire resistance genes from non-human sources.

350 351
RECOMMENDATIONS

RECOMMENDATIONS
Antimicrobial
classification

352 353
Is it possible to rank antibiotics
R.17
according to 1st or 2nd choice?
Yes but...

n A consensus of the American Col- n It is difficult to classify anti-


lege of Veterinary Internal Medicine microbial drugs as there are not
defined four categories of antibiotics evidence-based categories.
on the basis of their use: 1st line (or
n However, it is widely accepted that
RECOMMENDATIONS

RECOMMENDATIONS
primary), 2nd line (secondary), 3rd line
(tertiary) and restricted or voluntarily 3rd generation cephalosporins and
prohibited antibiotics. fluoroquinolones should not be used
as 1st line antimicrobials because
n Secondary or higher use categories they are critically important to treat
should only be used if primary use life-threatening infections in humans.
drugs are not appropriate and should
be based on culture and sensitivity
testing.
The prescription of an antibiotic should take into account its category: first-line or second-line.

To facilitate appropriate empirical se- use agents are not appropriate based on
lection of antimicrobial drugs by veteri- culture and AST results. in humans)4. use categories, when 1st line drugs are
narians on a routine basis, a consensus useful in most infections. In a veteri-
Drugs that are very important for human Definition of use categories and exam-
statement of the American College of nary teaching hospital, despite a case-
and animal health care, especially those ples are presented in Table 1. However,
Veterinary Internal Medicine (ACVIM) load skewed toward critically ill referral
most recently developed and those that development of specific categories, tak-
proposed a categorization of antimicro- cases, drugs designated as first-line
have extended spectra of activity and ing into account the type of infection, the
bials into primary, secondary and tertiary accounted for > 90% of 21,152 prescrip-
are efficient against the most resistant patient characteristics, antimicrobial re-
use categories4. tions between 1995 and 20047.
bacteria, should be classified for tertiary sistance patterns and drug factors, are
The primary (1st line) use category in- use (3rd line). Tertiary use drugs should needed (see Disease fact sheets in part Another reason explaining the empirical
cludes older antimicrobials and those only be prescribed for animals with 1 of the book). Recently, such guidelines prescription of broad-spectrum 2nd line
with a narrower spectrum of activity (see clinically important infections caused have been proposed for canine super- drugs is the delay in receiving appropri-
Table 1 p.356 and recommendation R.13). by bacteria that have been demonstrat- ficial bacterial folliculitis by the Inter- ate therapy based on laboratory results,
ed to be resistant to all primary and national Society for Companion Animal which may affect the clinical outcome
Drugs assigned to the secondary (2nd line)
secondary use drugs. Infectious Diseases2. FECAVA has also and survival in critically ill patients.
use category include newer antimi-
developed a poster for recommended Patients classified as receiving inap-
crobials with an extended spectrum The last category includes antimicro-
therapy of common clinical conditions propriate empirical antimicrobial ther-
of activity compared with primary use bial agents for which the clinical value
(www.fecava.org/sites/default/files/ apy have indeed at least a 36–48 hour
antimicrobials and those of added to human medicine is so important that
files/AMR%20theraphy.pdf). delay in receiving appropriate antimi-
importance in the treatment of serious their use should be voluntarily prohib-
or frequently resistant infections in hu- ited in animals (e.g. drugs that are not A common mistake is to consider that crobial therapy (while awaiting culture
mans. Secondary or higher use antimi- licensed for veterinary use and are es- primary use antimicrobials are less effi- results) when compared to those giv-
crobials should be used only if primary sential for treating resistant infections cient than those in secondary or tertiary en appropriate empirical antimicrobial

354 355
R.17
Is it possible to rank antibiotics according
to 1st or 2nd choice? Yes but...

Table 1 (continued)
Table 1 - Categorization of systemic antimicrobials.
Use category Definition and guidance for use Examples
Use category Definition and guidance for use Examples
• 3 line antibiotics are antibiotics
rd

• 1st line antibiotics are antibiotics • Penicillins that are of great importance to ani-
that are well established with good • 1st generation mal and human health especially for
Primary/ the treatment of multidrug resistant
evidence of high efficacy and safety. cephalosporins
1st line Ideally, they should be narrow-spec- bacteria, and where resistance is
• Amoxicillin±clavulanate
Licensed for trum. They are as potent as 2nd and more likely occur following use
RECOMMENDATIONS

RECOMMENDATIONS
• Trimethoprim and/or is of great concern in
3rd line drugs used in the appropriate
companion sulfonamides
circumstances. veterinary and human healthcare.
animals • They should be used wherever • Tetracyclines Many of these drugs are not licensed
appropriate and possible. • Lincosamides for companion animals, and there- • 3rd and 4th generation
fore data on clinical breakpoints, cephalosporins
Tertiary/
• 2nd line antibiotics are often efficacy and safety may be lacking. other than cefovecin
3rd line • They must only be used where • Rifampicin
broad-spectrum antibiotics that are
important for animal and human there is culture evidence to show • Fosfomycin
health and in which resistance is Narrow spectrum: that 1st or 2nd line antibiotics will
more likely to occur following use • Aminoglycosides not be effective and where topical
and/or is of greater concern in • Metronidazole therapy has been ineffective or is not
Secondary/ veterinary and human healthcare. • Macrolides feasible.
• Critically important antibiotics • The use of 3rd line drugs must be
2nd line supported by AST, although these
should only be used where C&AST Broad spectrum:
Licensed for results or good clinical and • Chloramphenicol drugs may be started in life-threate-
companion epidemiological evidence indicate ning conditions while waiting for the
that 1st line antibiotics will not be Critically important ABs: culture results.
animals
effective. Wherever possible, the use • Fluoroquinolones • Glycopeptides:
of 2nd line drugs should be supported • Cefovecin (3GC) vancomycin, teicoplanin
by C&AST. • Carbapenems and
• Some antibiotics are classified as Restricted, • These drugs are vitally important
monobactams
2nd due to their toxicity, but not due to voluntarily to human health so should never be
• Oxazolidones: linezolid
their activity (e.g. aminoglycosides). prohibited used in animals.
• Lipopeptides: daptomycin
• Riminofenazines:
clofazime

356 357
R.17
Is it possible to rank antibiotics according
to 1st or 2nd choice? Yes but...

therapy. It was shown that this delay did usefulness for treatment of serious in-
not affect mortality in dogs with pneu- fections in humans and animals. Cur- Why should the use of Critically Important
monia5 or septic peritonitis1. Larger, rently, given the paucity of data available Antibiotics be avoided?
prospective clinical studies that include on these aspects in veterinary medi-
various subgroups of patients are how- cine, especially regarding the impact
ever needed to provide clear evidence of of the use of antimicrobials on resist- Not all antibiotics have the same critical importance for human health.
the benefit of early and appropriate an- ance emergence, more information is
National and European recommendations are based on the avoidance of selec-
timicrobial therapy3. required to adequately assign drugs to
ting resistance to critical antibiotics in bacteria in animals that could be trans-
tiers8. It should be also emphasized that
Moreover, the clinical seriousness of an mitted to humans, i.e. (in order of importance):
RECOMMENDATIONS

RECOMMENDATIONS
the list of Critically Important Antimicro-
infection in a dog or a cat is not a valid
bials for human medicine by the World - Last-resort antibiotics for humans (e.g. carbapenems),
reason by itself to justify the immediate
Health Organization in 20119 includes
prescription of 2nd line antimicrobials as - 3rd and 4th generation cephalosporins (e.g. cefovecin),
some antimicrobials (e.g. amoxicillin,
initial treatment.
ampicillin…) considered as primary use - Fluoroquinolones.
While categorization has clearly contrib- drugs by veterinarians. It is however
The use of these Critically Important Antibiotics should therefore be limited
uted to the appropriate use of antimi- widely accepted that only 1st and 2nd line
to individual clinical cases that cannot be treated by other antimicrobials (e.g.
crobials on a routine basis by veterinar- drugs should be used for treatment of
multidrug resistant infections). Culture and AST should be performed to make
ians over the last 10 years, it is however canine and feline infections and that
sure that no other antibiotic can be used instead of a CIA.
difficult, as stated in the second ACVIM 3rd and 4th generation cephalosporins
consensus statement8, to assign drugs and fluoroquinolones should not be
to different tiers as there are not evi- used as 1st line antimicrobials. Use of
dence-based categories. Antimicrobials tier-based antimicrobial selection is
should be assigned to tiers according to clearly helpful for initial drug prescrip-
the spectrum of activity, the effect on tion, but more information is needed for
commensal microbiota, the likelihood of appropriate categorization of antimicro-
resistance emergence, and the clinical bial drugs. n

358 359
RECOMMENDATIONS

360
Causes of failure

361

RECOMMENDATIONS
What are the key causes of antibiotic treatment
R.18
failure and what is the importance of resistance?
What to do in a case of antibiotic treatment failure?
Lack of drug efficacy at the infection site
may be due to physiological (e.g. brain-
or prostate-blood barrier) or pathologi-
cal barriers (e.g. abscess wall, biofilm,
presence of pus and other organic mat-
n Treatment failure can be a result of in human medicine bacterial ter interfering with antibiotic activity or
different factors influencing the clini- resistance is the main cause of pathogen intracellular location).
cal efficacy of antibiotic therapy either treatment failure.
alone or together. Inappropriate dosages also affect
n The veterinarian can take a certain
treatment outcome by hampering the
RECOMMENDATIONS

RECOMMENDATIONS
n Key causes to be considered in case number of measures to avoid resist- achievement of adequate drug concen-
of treatment failure include: ance-related failures: trations at the infection site. Thus it is
• an unjustified antibiotherapy, com- • carry out a microbiological diag- essential that the patient is weighed to
bined with a mistaken diagnosis of nosis of the pathogenic agent rather calculate accurately the correct dosage
bacterial infection, or not accompa- than an epidemiological one, based on the actual body weight. Pre-
nied by essential measures (abscess • measure the sensitivity to antibiot- scription of tablets that are designed to
lancing, draining of infection sites...), ics of the strain responsible for the facilitate dosage by the owner may be
• a bad choice of drug: spectrum or infection. Sample for culture and AST another approach to avoid underdosage.
lack of efficacy at the infection site, if the previous treatment was empir- Non-compliance is another important
• a wrong dose regimen: low dose, ical or sensitivity results are unrelia- cause of antibiotic treatment failure. In
frequency or length, non-compliance ble, human medicine, it has been estimat-
by pet owners, • adhere to the recommended doses ed that approximately 40% of patients
• a suppressed host immune status. and the optimal administration pro- do not adhere to antibiotic treatment2.
n Bacterial resistance is involved in cedures for time-dependent or con- The patterns of non-compliance in-
centration dependent antibiotics, Non-compliance is an important cause of anti-
a bad choice of drug or a wrong dose clude failure to start the therapy, delay biotic treatment failure.
regimen, but its relative importance • verify that the owner complies with in the start of the therapy, omission of
among the other causes of failure is the prescription (see recommenda- single doses, changes in time intervals
difficult to quantify. Based on studies tion R.21). between doses, premature stopping of human medicine2, non-compliance may
treatment or use of left-over antibiotics. also be due to owner’s beliefs, cost of
Key causes of antibiotic treatment failure Uncooperative or aggressive pets are a
recognized cause for a lack of compli-
antibiotic, antibiotic bad taste, frequent
dosing, long treatment time, side ef-
The role played by bacterial resistance ceptible strains3,1. However, the correla- ance in veterinary medicine (see recom- fects, owner’s forgetfulness and rapid
in treatment failure has not been quan- tion between treatment failure and re- mendation R.21). Based on research in improvement of symptoms.
tified in veterinary medicine. Human sistance has been poorly investigated in
studies have shown that clinical condi- veterinary medicine.
tions do not improve in most patients It is generally assumed that the immune
What to do in case of antibiotic treatment failure?
treated with antibiotics to which the status of the patient influences the out- Treatment failure may be consequent to cause of failure taking into considera-
cultured strains are classified as re- come of antibiotic treatment, especially a variety of factors influencing the clin- tion both anamnestic and clinical data.
sistant (50-80%), whereas the rates of when bacteriostatic drugs are used ical efficacy of antibiotic therapy acting Assuming that the prescribed drug is
treatment failure are markedly lower because it requires the host immune re- alone or in combination. Thus it is es- known to penetrate and be effective at the
(3-10%) in patients infected with sus- sponse to cure infection. sential first to identify the most likely infection site and was not underdosed

362 363
R.18 What are the key causes of antibiotic treatment failure
and what is the importance of resistance?
What to do in a case of antibiotic treatment failure?

in the prescription, the following steps


should be taken:
• The possible causes of treatment fail-
ure are reviewed based on anamnesis
and clinical records. A microbiological
diagnosis (e.g. cytology) should be car-
ried out.
• An appropriate sample is taken and
submitted to a microbiology laboratory
RECOMMENDATIONS

RECOMMENDATIONS
for culture and sensitivity testing if the
previous treatment was empirical or
based on sensitivity results that are re-
garded as old or unreliable. Multidrug resistant
• Another antibiotic is chosen based on
available sensitivity results if the previ- infections
ous treatment was based on sensitivity
results that are regarded as reliable.
• In case of suspected non-compli-
ance, the owner is educated about the
In case of suspected non-compliance, the
importance of compliance and a new owner is educated and a new treatment
treatment course is established using course is established using the least deman-
the least demanding treatment option ding treatment option.
(i.e. short-course antibiotic therapy with
infrequent dosing, convenient dosage
form and minimal adverse effects). Good • A bactericidal drug is chosen if the pre-
communication and a trusting relation- vious treatment was bacteriostatic and
ship with the pet owner is key to secure the immune status of the patient is sup-
compliance. The pet owner should be pressed.
comfortable enough with the vet to ex- • If none of the possible causes can be
press his/her concerns if not able to excluded, all the actions listed above
deliver the proposed therapy to their should be implemented in the new
animals (see recommendation R.21). treatment. n

364 365
R.19
How to deal with multidrug
resistant infections? What influences treatment choices?
The extent and severity of the infection exceeded at the target tissues. It may be
strongly influence treatment choices. It possible to achieve this even for resist-
is difficult to make precise treatment ant isolates by increasing the systemic
n Use clinical signs and cytology to health even if the infection is recommendations for these cases, as dose or using topical therapy.
determine the extent and severity of susceptible. most systemic antimicrobial options
Topical antiseptics can be highly effec-
the infection. will be inappropriate. Clinicians must
n Bacterial biofilms may need spe- tive, even against multidrug resistant
therefore carefully evaluate clinical
n Use bacterial culture and antibiotic cific measures, including products bacteria (see Tables 1 and 2, Figures 1
RECOMMENDATIONS

RECOMMENDATIONS
signs, cytology and culture results to
susceptibility testing of representative with anti-biofilm activity (e.g. acetyl and 2). MICs are reported in µg/ml rang-
select the appropriate antimicrobials,
samples. cysteine, TrizEDTA and detergents) es assuming that the antibiotic will be
route of administration and duration of
and/or removal of implants.
n Obtain minimum inhibitory concen- treatment. given systemically. Topical therapy,
trations (MICs) wherever possible. n Use strict barrier nursing, hygiene The minimum inhibitory concentra- which delivers mg/ml antibiotic con-
and infection control measures to tion (MIC) is the lowest concentration centrations, can overcome apparent re-
n Always use topical antiseptic therapy prevent spread of the bacteria to the of an antibiotic that completely inhibits sistance. Using antimicrobial sensitivity
wherever possible – consider chlorhex- environment and other patients. growth of the bacteria. MIC data reveals tests to predict the response to topical
idine-based shampoos, sprays, and the exact concentration that must be therapy is therefore misleading.
n Give advice to the owners about ef-
wipes; medical-grade honey ointments
fective hygiene measures to minimise
and dressings; hypochlorous acid
the risk of zoonotic colonisation and
sprays and dilute bleach solutions
infection.
(see Figures 1 and 2).
n Stop antibiotic therapy as soon as
n Consider topical antibiotics – effec- the infection has resolved.
tive drugs include mupirocin, fusidic
acid, silver sulfadiazine and silver sul- n Culture appropriate carriage sites
fadiazine combined with gentamicin (e.g. nose and perineum, urine or fae-
ces) to determine whether the patient

© courtesy Dr Stephanie Horne


or marbofloxacin.

© courtesy Dr Stephanie Horne


is still colonised with the antibiotic
n Treat the underlying cause of the resistant bacteria.
infection (see Figures 3 and 4).
n Allow colonised animals to recover
n Only use systemic antibiotics if ab- in the community – avoid antibiotics
solutely necessary, and never use and veterinary visits and give advice
drugs of critical importance to human on routine care and hygiene.

Figure 1 - MRSP-associated infection and wound Figure 2 - Three weeks later there was com-
breakdown after a hind limb amputation in a plete resolution of the infection following re-
cat. moval of the Penrose drain and sutures, and
twice daily cleaning with a 0.011% hypochlo-
rous acid solution.

366 367
R.19
How to deal with multidrug
resistant infections?

The identity of the organism guides the ronmental (e.g. Pseudomonas) bacteria.
choice of antimicrobial, but decisions These are not primary pathogens, and Table 1 - Effective topical antimicrobials.
should be based on clinical signs and almost all infections are secondary to an Superior in vitro efficacy than other antimicrobial shampoos.
cytology. Topical antibiotics, moreover, underlying problem. Successful resolution 2-4% Effective as sole therapy in MRSP-associated canine pyoderma.
may not be metabolised and excreted often requires management of the pri- chlorhexidine Residual activity; can be used 2-3 times weekly for 5-10 minutes.
and may therefore have a much longer mary disease (e.g. treating the atopic shampoos 2% chlorhexidine and 2% miconazole show synergistic activity
duration of activity compared to system- dermatitis, managing diabetes mellitus against Staphylococcus pseudintermedius.
ic drugs. Options include using antibi- or removing foreign bodies, sutures and Highly effective in vitro compared to other antimicrobial and
otic solutions to flush joints or cavities, 0.15% cleansing wipes.
implants; see Figures 3 and 4). For ex-
RECOMMENDATIONS

RECOMMENDATIONS
nebulised solutions for respiratory in- chlorhexidine Little to no efficacy against Pseudomonas and ESBL-E. coli.
ample, in atopic patients with pyoderma, wipes
fections, antibiotic creams, gels or oint- treatment with glucocorticoids alone or No residual activity; use at least once daily.
ments for ears, eyes, skin and wounds, glucocorticoid-antibiotic combinations 0.15% Broad spectrum in vitro activity.
and antibiotic impregnated beads and is more effective than the use of anti- chlorhexidine High concentration of TrizEDTA potentiates chlorhexidine but
foams for joints, cavities and wounds biotics alone. Antimicrobial resistant and TrizEDTA there is no evidence of synergistic antimicrobial activity.
(see Table 2). infections in dogs can rapidly improve 0.011% Highly effective in vitro.
Most antimicrobial resistant infections following removal of foreign bodies, su- hypochlorous No residual activity; use at least once daily.
are opportunistic, involving commensal tures and implants in conjunction with acid
(e.g. MRSA, MRSP and E. coli) or envi- simple topical antimicrobial therapy. Highly effective in vitro.
Diluted bleach Use higher concentrations with care.
Little to no antimicrobial activity by itself.
High concentrations potentiate the antimicrobial activity of
TrizEDTA gentamicin and marbofloxacin but there is no evidence of
synergistic antimicrobial activity.

Use of 2nd line and last resort systemic antibiotics


Second-line and last-resort systemic penetration to the target tissue. The
antibiotics (e.g. rifampin, chloramphe- underlying condition must always be
nicol, aminoglycosides, 3rd or 4th genera- managed, as treatment may otherwise
tion cephalosporins, anti pseudomonal just select for more resistance among
©Tim Nuttall

©Tim Nuttall

penicillins and fosfomycin) should only pathogenic and commensal bacteria.


be used where absolutely necessary, It is questionable whether third-line
i.e. when no first or second-line drugs antibiotics should be used if antibio-
are appropriate and topical therapy has tic therapy will not affect the overall
Figue 3 - MRSP-associated superficial bacte- Figure 4 - The infection completely resolved
not been effective or is not feasible. The clinical outcome. Drugs that are vital-
rial folliculitis in a dog with atopic dermatitis. following management of the atopic dermatitis choice of drug (see Table 3) should be ly important for human health (e.g.
with cyclosporine and daily soaks with diluted made following culture of representative vancomycin, teicoplanin, linezolid
bleach. material, taking into account underlying and carbapenems) should not be used
conditions, concurrent medication and in animals. Stop antibiotic therapy as

368 369
R.19
How to deal with multidrug
resistant infections?

before applying topical antibiotics where biofilms remain a significant clinical


Table 2 - Topical antibiotics (combinations with another antibiotic / antifungal not included). appropriate. Acetyl cysteine liquefies challenge and may necessitate removal
Broad spectrum antimicrobial activity. biofilms, facilitating removal and pene- of sutures, catheters and implants.
1% silver tration by antimicrobials. Nevertheless,
Potentiates gentamicin (0.3%), amikacin (0.1%) and marbofloxacin
sulfadiazine
(0.2%) but no evidence of synergistic antimicrobial activity.
Neomycin
Broad spectrum; usually combined with a glucocorticoid. Minimising the spread of resistant bacteria
Gentamicin
Great care should be taken to prevent resistant bacteria. However, they should
Fusidic acid Narrow spectrum; topical application highly effective against dissemination of antimicrobial resis- not be treated with antibiotics, as this
RECOMMENDATIONS

RECOMMENDATIONS
MRSA and MRSP. tant bacteria in veterinary healthcare may select for further resistance, re-
Mupirocin Mupirocin may be reserved for use against MRSA in humans in environments. Similarly, while most duce the diversity of commensal bac-
some countries. antibiotic resistant bacteria are oppor- teria and lead to persistent carriage.
Antibiotic tunists and pose little risk to healthy Simple hygiene measures are enough
dilutions in people and animals, owners should be to limit spread and most animals will
TrizEDTA: given clear and effective advice on hy- lose colonisation with multidrug resis-
0.6% enrofloxacin Effective against Pseudomonas; gentamicin and amikacin giene and infection control. Clinically tant bacteria without the need for any
0.2% marbofloxacin solutions can be effective against Pseudomonas, MRSA/MRSP healthy animals that have recovered further measures (see recommendation
2.7% ticarcillin and ESBL-E. coli. are often colonised with antimicrobial R.24). n
1.7% ceftazidime
0.3% gentamicin
0.1% amikacin

soon as the infection has resolved. This • normal cytology,


decision should be based on: • where appropriate, negative cultures
• the complete resolution of clinical (remember that animals may still be
signs associated with the infection culture positive for commensal bacte-
(remembering that clinical signs as- ria such as MRSP or E. coli in the ab-
sociated with the primary disease may sence of infection).
still be present),

Importance of biofilms in treatment


Many antimicrobial resistant bacteria leading to treatment failure, develop-
produce biofilms, which can complicate ment of resistance and/or relapse af-
otitis, bacterial overgrowth syndrome ter treatment. Where possible biofilms
and urinary tract infections. Biofilm should be removed by thorough bathing,
forms on implants, catheters and su- wound cleansing and ear flushing. Triz-
tures, and protects the bacteria against EDTA may facilitate antimicrobial pe- Consider topical antiseptic products for multidrug-resistant infections.
topical and systemic antimicrobials netration into biofilms and can be used

370 371
R.19
How to deal with multidrug
resistant infections?

Table 3 - Systemic antibiotics that may be effective in antimicrobial resistant bacterial infections.

Antibiotic Dose Notes


Check for inducible clindamycin
resistance (PCR, D-zone test or
Clindamycin 11 mg/kg q 12-24h PO
concurrent resistance to
erythromycin).
Chloramphenicol 50 mg/kg q 8h PO (dog)
RECOMMENDATIONS

RECOMMENDATIONS
50 mg/cat q 12h PO (cat) Non-regenerative anaemia; inhibits
hepatic microsome enzymes.
Florfenicol 25-50 mg/kg q 8h SC
Amikacin
Gentamicin
15-30 mg/kg q 24h SC
9-14 mg/kg q 24h SC Ototoxic and nephrotoxic.
Prevention of resistance
Tobramycin 9-14 mg/kg q 24h SC
Effective against MRSA; most MRSP
15-30 mg/kg q 12-24h isolates are resistant.
Trimethoprim- PO or SC Adverse effects include kerato-
sulfadiazine (dose may differ for other conjunctivitis sicca, hypothyroidism,
potentiated sulphonamides) blood dyscrasias, immune-mediated
reactions and urine crystals.
Effective against MRSA; most MRSP
Doxycycline 5-10 mg/kg q 12-24h PO
isolates are resistant.
Minocycline 5-15 mg/kg q 12-24h PO
May cause oesophageal irritation.
Ceftazidime 20-50 mg/kg q 8h IV/IM
Anti-Pseudomonas.
Cefoperazone 22 mg/kg q 8 hours IV/IM
ESBL-associated urinary tract
Nitrofurantoin 4 mg/kg q 8h PO
infections.

Rifampin 5-10 mg/kg q 12-24h PO Hepatotoxic.

Effective against MRSA and MRSP;


ESBL-associated infections,
Fosfomycin 40-80 mg/kg q 12h PO especially in the urinary tract.
Appropriate dose in dogs not yet
fully validated.
Please note that some countries prohibit the use of some human antibiotics not licensed for animals, the
off-label use of licensed drugs and/or the use of certain critical drugs even if there is evidence of sensitivity
or efficacy.

372 373
How can the development of
R.20
resistance be limited when using
the MPC to be reached at the site of in-
antibiotics? (timing, dosage, duration) fection and contribute to slowing down
development of resistance to concen-
tration-dependent drugs for which
resistance mainly evolve by chromoso-
n Limit use of antibiotics to only as and third generation cephalo- mal mutations (e.g. fluoroquinolones).
necessary. Avoid them whenever pos- sporins). There is no consensus on whether a sim-
sible (e.g. superficial pyoderma, ab- ilar approach may be useful to prevent
n Concentration-dependent drugs such
scesses). resistance to time-dependent antibio-
as fluoroquinolones should be admin-
RECOMMENDATIONS

RECOMMENDATIONS
n Whenever possible, the antibiotic istered using the highest dosage pos- tics for which resistance mainly evolves
choice should be guided by cytology sible to prevent selection of resistant by horizontal gene transfer. Some stud-
or sensitivity testing. mutants as well as to enhance clinical ies indicate that acquisition of resis-
efficacy. tance by horizontal gene transfer may
n When treating empirically, first-line also be avoided to some extent when the
antibiotics should be preferred over n Underdosing and irregular admin- MPC is reached11.
second-line agents with broad spec- istration intervals should be avoided
trum of activity (e.g. fluoroquinolones for all antibiotics. There is a lack of scientific evidence to
recommend how long the duration of
treatment should be in order to limit
Sensitivity testing is useful to tailor ther- This is why empirical use of broad-spec- development of resistance. As a matter
apy to the susceptibility profile of the in- trum antibiotics, in particular fluoro- of principle, unnecessary treatment
fecting strain, therefore avoiding use of quinolones, cefovecin or other third should be avoided after the patient has
ineffective antibiotics. The information generation cephalosporins, should be Underdosing should be avoided to limit re- recovered from the infection. In hu-
provided by cytology to guide antibiotic avoided. Various studies in dogs2-5 and sistance. Weighing the patient is essential to
mans there is an increasing consensus
choice is not as accurate as for sensi- calculate accurately the correct dosage.
livestock animal species6-10 indicate that that treatment duration can affect the
tivity testing but assists the decision on these drugs are likely to promote selec- selection of antibiotic resistance. When
whether antibiotic therapy is needed. tion of multidrug-resistant bacteria of comparing recommendations between
Furthermore, cytology results can also should only be used as second or third-
high clinical relevance such as MRSA, line agents to preserve their efficacy for human and veterinary medicine, it is
be used to select drugs active against MRSP and ESBL-producing strains. evident that for some infections (e.g.
treatment of complicated infections.
specific groups of organisms based on These bacteria are per definition resis- urinary tract infections) duration of
Dosing regimens should be carefully se-
the morphology of the infecting strain tant to third generation cephalosporins treatment is longer in animals12. More
lected on the basis of pharmacokinetic
(Gram-positive cocci vs. Gram-negative and display relatively high rates of fluo- research is needed to optimize treat-
and pharmacodynamic properties that
rods). This is why cytology should be roquinolone resistance. This is why ment duration in relation to both clinical
prevent emergence of pre-existing and
performed routinely to guide antibiotic we recommend that veterinary fluoro- efficacy and prevention of resistance de-
newly formed mutants. The concentra-
choice in the treatment of pyoderma, quinolones (enrofloxacin, marbofloxa- velopment.
tion that restricts the emergence of re-
otitis or urinary tract infections1.
cin and pradofloxacin) and cefovecin, sistant mutants within a susceptible po- For more information on rational an-
The broader the spectrum of an antibiotic, which is the only extended-spectrum pulation is defined as Mutant Prevention timicrobial use and prevention of re-
the wider the impact on the commensal long-acting cephalosporin authorized Concentration (MPC). There is increa- sistance development, please refer to
flora and on selection of resistance. for use in companion animals in the EU, sing evidence that higher dosages allow Synopsis chapters. n

374 375
RECOMMENDATIONS

376
Compliance

377

RECOMMENDATIONS
How to obtain good client
R.21
compliance (to limit the
development of resistance)? Good prescribing
n Select the antimicrobial that is the n Prescribe only the quanti-
most appropriate for the likely/con- ty necessary for the duration of the
firmed pathogen involved, condition therapeutic course.
Good communication and organ or system affected. How-
n Opt for shorter therapeutic course
Good communication is important to n the requirement to: ever, also consider the level of com-
durations whenever possible.
engage clients and ensure compli- • complete the full therapeutic pliance you are realistically likely to
ance with prescribed therapies. Vet- course, achieve (taking into account the route n Minimise the number of drugs in-
RECOMMENDATIONS

RECOMMENDATIONS
erinarians should allocate time dur- of administration, dose, dosing fre- cluded in the therapeutic plan.
• contact the vet if the client needs
ing the consultation to discuss and quency and duration of therapy, ani-
to discuss any issues or queries they n Select the most convenient fre-
agree a therapeutic plan with their mal characteristics and after discus-
might have during the therapeutic quency of dosing for the client, tak-
client and explain: sion with the client what they are able
course, ing into account their availability and
or willing to do).
n the risk of treatment failure, dis- • attend follow-up consultations willingness to administer medica-
ease recurrence and development of (e.g. for therapy effectiveness as- n Prescribe palatable tablets or tools tions.
antimicrobial resistance if the thera- sessment and discussion of possible e.g. pill poppers to aid tablet or drug
Show how to administer the treat-
n
peutic plan is not followed correctly, further therapeutic options if re- administration.
ment to the animal.
n the frequency of dosing (e.g. explic- quired), n Select formulations with the correct
itly explaining every 12 hours instead • ensure leftover drugs are not used dosing and for ease of administration.
of twice a day), to treat recurrent conditions and/or
new conditions in their animals or
n the correct dose, Good service and follow-up
someone else’s; these should be
n how to monitor the animals for any disposed of safely. Consider offering: n Follow-up calls to discuss pro-
potential adverse effects, gression of therapy.
n Administration of therapy by a member
of staff (e.g. nurse consultations), n Provision of detailed written in-
n Reminder phone calls or SMS mes- structions to pet owners regarding
sages for the frequency of dosing, the type of medication prescribed and
n Reminder phone calls or SMS mes- method of administration.
sages for follow-up consultations,

How compliant are pet owners in the adminis-


tration of medications?
In veterinary medicine, compliance is defined data regarding compliance levels in pet
as ‘‘the extent to which owners adhere animals; studies focused on assessing
Veterinarians should allocate time during the consultation to discuss and agree the therapeutic
plan with their client. to instructions when giving prescribed compliance in small animal practice
drugs to their animals’’6. There is scarce have reported varied levels between 27%

378 379
R.21
How to obtain good client compliance
(to limit the development of resistance)?

and 84%, depending on the definition of or by underdosing, can result in treat-


compliance applied, frequency of dosing ment failure, recurrent conditions Table 1 - Barriers to compliance with prescribed therapy in veterinary practice.
and duration of therapy considered, and the development of antimicrobi-
n Owner inability to effectively administer medication:
species and country where the study al resistance due to selective pres-
was conducted6,7,9. Veterinary surgeons sure upon microbial populations2,8. • Owner cannot master technique to administer the treatment,
often assume high levels of compliance This may additionally lead to inaccu- • Due to dosing frequency or duration (e.g. unavailability, forgetfulness),
by pet owners9. Lack of compliance to rate assessment of therapeutic effi- • Dog or cat not amenable.
prescribed therapies, either through cacy and mistrust in the initial diag- n Owner interrupts treatment course because:

failure to complete a treatment course, nosis of the condition being treated2. • Adverse effects are observed (drug is perceived as “harmful” to pet),
RECOMMENDATIONS

RECOMMENDATIONS
missed or incorrect dosing frequencies • The animal gets better (pet perceived as “cured”),
• No improvement is observed during the treatment (drug perceived as “ineffective”).
n Cost of the therapy is too high (client unable or unwilling to pay).
What are the barriers to compliance? n Inadequate consultation time to discuss prescribed therapeutic plan.

There are several factors that can affect routes www.youtube.com/user/iCatCare). n More than one individual involved in the care of the animal.

compliance in veterinary settings that may n Animal fails to return to the clinic for follow-up assessment and further medication.
Good communication is clearly a key
act as barriers (Table 1). Most of these
factors are client-related. Nevertheless, factor in the establishment of a rela-
the veterinarian and veterinary team tionship of trust and promoting compli- Compliance has been reported to de- perceive that their animal’s condition has
play an important role in the education ance by clients. It has been reported that crease considerably (up to a nine-fold) improved7. The occurrence of unexpect-
of pet owners regarding the importance pet owners valued the time committed with increased frequency of dosing of ed adverse effects can also be a cause
of being compliant with instructions by vets to the consultation, which might antimicrobials1 and it is also known to for non-compliance; although antimicro-
provided for prescribed therapies6,7,9. indicate that their level of compliance be a particular issue when dealing with bials are often perceived as being “safe”
The ability of a client to administer a might be affected by the perceived ded- conditions that require long-term ther- drugs in animals, adverse or side effects
medication is often over-estimated. In a apy, such as deep pyoderma in dogs7, include allergic reactions, gastrointesti-
ication of the vet to the care of their
recent study focused on pets and horse formulations that are not easy to admin- nal signs (e.g. vomiting and diarrhoea),
pets6. Active involvement of clients
owners, it was reported that none of ister due to the route of administration pyrexia, cartilage abnormalities and
in the decision-making of a suitable
the participating veterinarians (n=57) or due to animal behaviour (e.g. tablets tooth discoloration in young animals (e.g.
therapeutic regimen is essential and for cats or topical ear preparations in
provided written information on drug fluoroquinolones and tetracyclines, re-
should be adjusted to their availability1,5. dogs)4,7. Complex therapeutic protocols
administration and only 5% of them spectively), amongst others3.
This factor has been associated with can also impact the level of compliance
demonstrated how to administer tab- non-compliance rates of up to 50% in a It is therefore necessary to maintain good
lets to animal owners8. Education of as these may be difficult to remember
short-therapy study in dogs5. Provision communication with clients throughout
the owner in techniques of medication or implement by clients which may lead
the duration of the therapeutic course
of explanations of the condition suf- to loss of engagement3,4.
administration is one factor that can be in order to be able to identify potential
easily addressed with demonstrations fered by their animal4, repeated instruc-
Completion of prescribed therapy is a barriers to compliance that might com-
and provision of resources that can be tions on therapy prescribed and expla-
major issue, as clients might be tempted promise therapeutic success and may
referred to at home (prepared resources nation of effects of prescribed therapy to ‘‘self-assess’’ the health of their result in the emergence of antimicrobial
are readily available e.g. BSAVA drug infor- have been shown to improve compliance animals and decide to stop therapy if they resistance7,9. n
mation sheets and International Cat Care amongst animal owners, with the former
YouTube videos demonstrating adminis- improving client compliance by 31% (i.e.
tration of medications to cats via various compliance levels reached 76.9%)8.

380 381
R.22
How do I get the pill into the animal?
Top ten tips.

Veterinarians and nurses have an important practical role to play, beyond


simply dispensing the medication, by ensuring that the owner will be able
to administer the medication correctly.
1. Involve the owner from the start; it is and without causing oropharyngeal or la-
RECOMMENDATIONS

RECOMMENDATIONS
important to realistically assess owner ryngeal trauma.
willingness, availability and ability to treat
7. Discuss the importance of building a
their pet.
positive association with administration
2. Look for antibiotics that have been de- of the medication (e.g. always follow tab-
veloped to be palatable; some feline prod- leting with a treat or something the pet
ucts may have an International Cat Care will enjoy such as a brush or play with a
‘‘Easy to give’’ award. favourite toy). This simple act will reduce
Palatable presentations will help compliance.
stress for the pet and owner and help the
3. Find out how the owner will plan to ad- owner to more successfully administer
minister the medication i.e. either directly medications. Whilst medication choices and pre- and for the correct duration. A course of
by tableting the pet or by disguising within scribing habits are critical in antibiotic medication can be stressful for both the
food or treats. Give specific suggestions of 8. Following any tablet or capsule with stewardship one fundamental aspect is owner and pet and this is undoubtedly
suitable palatable food and treats to hide a treat (or liquid) will reduce the risk of ensuring the antibiotic actually reaches more often problematic in cats.
medication in e.g. fish pate, canned tuna oesophageal irritation which is especial- the patient at the right dose, frequency
or sardines for cats, soft cheese or small ly important when administering clinda-
mycin capsules or doxycycline hyclate/
pieces of meat for dogs.
hydrochloride to cats, both of which have Step 1: Making medication choices
4. Consider the use of gelatine capsules, been associated with the development of Pet owner involvement is key to ensure by other factors for e.g. elderly or
these can be helpful if the tablet has a oesophageal strictures1,2. This also applies compliance with prescribed therapy. disabled clients may be less dexterous
bitter taste e.g. metronidazole, or if more to dogs. Time should be allocated during the and fearful or aggressive pets may not
than one medication needs to be given at consultation to determining whether tolerate restraint at home, which could
a time. 9. Urge the owner to contact the clinic if
there is a choice of appropriate antibi- endanger the owner-pet bond. In the
they have any queries or experience prob-
5. If the owner is planning to adminis- otic formulation e.g. tablet versus cap- case where pet owners are unable to
lems administering the medication.
ter the medication directly to the animal sule or liquid, and to discuss which will administer treatment, an option could
demonstrate how to do this effectively, 10. Provide the owner with reliable re- be easiest for the owner to administer. be offered to have the service provided
sources to refer to at home covering infor- Establish realistic expectations about by the veterinary staff. If not possible,
particularly considering the restraint re-
mation about the type of medication given owner availability when considering revision of the therapeutic course or
quired and provide explanatory supports.
and methods of administration e.g. BSAVA whether to dispense a medication that route of administration (e.g. injectable
6. If a pill popper is recommended ensure medicine information sheets or web link to requires dosing every 8 or 12 hours. versus oral) might need to be consid-
the owner knows how to use this safely videos (www.youtube.com/user/iCatCare). Consider whether the ability of the ered, in order to ensure that the animal
pet owner may also be compromised receives adequate treatment.

382 383
R.22
How do I get the pill into the animal?
Top ten tips.

Step 2: Owner education Step 3: Overcoming problems with administra-


Training and demonstration of tablet ad-
ministration by veterinary staff should
discuss planned use with the medica-
tion manufacturer. A loss of efficacy of
tion of medications
be offered to pet owners; this is often the drug may also occur if the pet owner It is important to maintain good com- attempts, providing support and en-
overlooked. Instructions on the safe oral decides to crush the tablet and deliver it munication with the pet owner during couragement may enable the owner to
administration of tablets (and other for- to the animal as a suspension for ease the therapeutic course, particularly if find a successful method. n
mulations such as pastes and liquids) of administration3. the veterinarian considers that there is
should be provided to avoid the risk of If the owner is planning to disguise the the risk of non-compliance. Encourage
pet owners to contact the clinic if they
RECOMMENDATIONS

RECOMMENDATIONS
biting and scratching by pets and to medication in a food or a treat, provide
prevent human injuries and infections e.g. specific suggestions of suitable treats have any difficulties with drug adminis-
Bartonella infection (cat scratch fever3,4). or foods to use e.g. meat or fish pastes tration to their pets. Simple reiteration
Gelatine capsules might be perceived (strong smelling), soft cheese or specif- of administration techniques or provid-
to be easier to administer by some pet ically designed products (e.g. treat sticks ing tips for disguising the food may en-
owners; they are available in various siz- and yoghurt paste). Some small tablets able the owner to overcome initial prob-
es; tablets can be placed within an empty can be easily hidden in soft malleable lems; alternatively bringing the pet back
capsule for administration (Figure 1). treats or small meatballs4. For the lat- into the clinic for a nurse appointment
ter, it is usually useful for the pet owner for pilling may be helpful.
to assess how the animal eats the meat- Demonstrating an understanding of the
ball (e.g. as a whole or in small pieces) challenges of medicating cats and dogs Figure 3 - Tasty paste formula treats can be
is important for the owner, especially useful to hide crushed medication within or
before hiding a dose within4. Consider can be used as a treat following administra-
the use of a pill crusher if disguising the when initial efforts are problematic. In tion of medications, to help develop a positive
tablet within food and advise the owner this situation the owner may feel that association with pilling. Soft malleable treats
to mix the powder with a small portion medicating the pet at home is impossi- can be used to disguise tablets.
of food (e.g. one teaspoon) before giving ble, however spending time discussing
the rest of the meal.
© Angie Hibbert

Figure 1 - Gelatine capsule prepared to ad-


minister three medications in a cat that is
difficult to pill repeatedly; co-administration
enables dosing, however the effect on phar-
© Angie Hibbert

macokinetics is unknown.

This could be the difference between


successful administration versus none Figure 2 - A pill popper may enable easier
at all. The effect of using gelatine cap- administration of tablets or capsules in some
sules on medication pharmacokinetics pets.
is unknown and it may be sensible to

384 385
RECOMMENDATIONS

386
Zoonotic impact

387

RECOMMENDATIONS
In which cases can resistance
R.23
selected in dogs and cats cause a
problem for human health?

n Companion animals can act as a and the general public in the


source and reservoir of resistant prevention and control of po-
bacteria such as Gram-negative (e.g. tential zoonotic risks derived from
Escherichia coli, Campylobacter spp., companion animals. Pet owners and
RECOMMENDATIONS

Salmonella spp.) and multidrug-re-

RECOMMENDATIONS
members of the same household with
sistant bacteria (e.g. ESBLs, MRSP) diseased or colonised animals, where
that are known zoonotic pathogens. there is a likelihood of having an im-
This is due to the regular use of an- paired immune system (e.g. young
timicrobials in everyday practice and children, elderly people, pregnant
to the close contact of pets with their women, immunocompromised or im-
owners and other animals within the munosuppressed individuals), should Companion animals can act as a source and reservoir of resistant bacteria such as Gram-negative
(e.g. Escherichia coli, Campylobacter spp., Salmonella spp.) and multidrug-resistant bacteria.
household and the community. not be directly involved in the care of
the animal. When visiting hospital-
n Responsible use of antimicrobials
should be promoted among veterinar-
ised pets, clients should follow good Antimicrobials, a risk factor
hygiene and infection control meas- Use of antimicrobials is a known risk healthy dogs21. Veterinarians should
ians in order to prevent and contain
ures; where possible the veterinarian factor for AMR emergence and spread follow current existing guidelines and
the spread of antimicrobial resistance
should explain the practice protocol in companion animals, as excessive and recommendations for responsible use
in animals under their care. Of par-
for hospitalised patients. misuse of these drugs can result in se- of antimicrobials whenever possible.
ticular importance is the moderation
of use of antimicrobials deemed of n Veterinary staff are also at risk lective pressure upon bacterial popula- Use of substances belonging to antimi-
critical importance in human medi- and could be exposed through direct tions6,12. In a recent study in dogs with crobial groups deemed as critically im-
cine to treat severe, life-threatening contact with colonised and infected pyoderma, Weese et al22 reported that portant for human medicine23 should be
infections such as cefovecin and fluo- animals under their care or through animals with a recent history of antimi- evidence-based, and supported by anti-
roquinolones. the contamination of their workplace crobial use were 10 times more likely microbial susceptibility results whenever
environment. to be infected with resistant strains possible as it is important to preserve
n Veterinarians have an important of meticillin-resistant Staphylococcus the efficacy of these antimicrobials to
role in the education of pet owners pseudintermedius (MRSP). This patho- protect both animal and public health12.
gen has also been isolated in clinically
The role of companion animals in so- organisms on a body surface (e.g. skin,
ciety has changed in recent years; pets mouth, intestines) without tissue inva-
Pets act as a reservoir
are often perceived as family members sion; the animal is clinically healthy. The acquisition of resistance by pathogenic the same household and in the commu-
by owners in high income countries15. and commensal bacteria in pets can nity7,9. Pets can also acquire resistant
Animals can become colonised and/or In infections, microorganisms invade pose a serious risk for public health: bacteria and resistance determinants
infected with resistant bacteria. Col- and cause damage to tissues and or- pets can act as a reservoir of resistant via foodborne sources; the increased
onisation refers to when there is the gans often leading to the occurrence of bacteria and resistance determinants popularity of raw meat diets in compan-
presence and multiplication of micro- clinical signs. to humans and other animals within ion animals can result in colonisation

388 389
R.23
In which cases can resistance selected in dogs
and cats cause a problem for human health?

of clinically healthy pets and infection


with resistant zoonotic pathogens10,19.
infection (e.g. UTIs in dogs) with resist-
ant strains of this bacteria, by compan-
Frequency of resistant bacteria
There is currently scarce surveillance ion animals, could pose a risk for indi- Occurrence of multidrug resistant (MDR) treats of animal origin (e.g. pig ears)12.
data on levels of antimicrobial resistance viduals in contact with these animals6. bacteria in companion animals is cur- MDR bacteria have been isolated from
in pathogenic and commensal bacteria Concurrent carriage of and infection rently an emerging public health issue dog faeces collected in urban areas,
in companion animals5,12,21. Healthy pets with resistant pathogens in companion that should not be overlooked5. Vanco- suggesting the potential risk for zoonotic
have been found to be carriers of resist- animals can also occur. In a recent study mycin-resistant enterococci (VRE)21 and transmission through environmental
ant commensal bacteria. Commensal in Canada, Beck et al.3 reported MRSP ESBLs9 are of particular relevance due contamination4,12. In a recent study
enterococci, which are part of the nor- isolation in the skin and carriage (in to the lack of therapeutic options and in Italy, enterococci were isolated in
RECOMMENDATIONS

RECOMMENDATIONS
mal gut flora of both companion animals nostrils and rectum) in 40.5% and 34.1% the risk of therapeutic failure8,9,17. The 16.3% of faecal samples collected from
and humans have zoonotic potential and of dogs affected with pyoderma (n= 173), level of carriage and infections caused in the environment (n=418); from these,
can cause opportunistic infections. A respectively. The study also reported the companion animals by VRE bacteria is 67.1% were resistant to three or more
study conducted in Denmark reported persistence of carriage in 35.3% of an- currently low but they can cause severe antimicrobial substances4. The recent
lower levels of carriage of resistant gut imals after clinical resolution of the infections in humans21. Levels of car- isolation in companion animals of MDR
bacteria in healthy dogs compared to condition, which poses serious public riage and infection by ESBLs in com- bacteria usually observed in healthcare
food-producing animals. Nevertheless, health risks. panion animals seem to be on the rise, settings (e.g. hospitals) such as MRSA
the same study detected ampicillin-re- which can pose a serious risk to animal (e.g. human clones 15, 16, 300)14,20, car-
Contact with pets is a known risk factor health and welfare as well as public bapenem-resistant Escherichia coli 5 and
sistant Enterococcus faecium strains.
for the transmission of resistant bac- health9. Other bacteria with zoonotic po- Acinetobacter baumannii 21, also suggests
This could have public health significance
teria5. Frequent social interactions and tential, in which MDR has been reported anthroponotic transmission of MDR bac-
as Enterococcus faecium can cause
shared environment has been shown to occurring sporadically in companion an- teria. Of particular concern are animals
bacteraemia and endocarditis in hu-
contribute to the transmission of resist- imals, are Pseudomonas spp. (e.g. ear belonging to households where humans
mans and ampicillin is one of the drugs
ant commensal and pathogenic bacteria and skin infections), Salmonella spp. have a previous history of hospitalisation
of choice for treatment. Carriage of
between animals and humans. Children and Acinetobacter baumannii21. MDR within the last six months7 or pets that
are particularly at risk of colonisation Salmonella typhimurium DT104 has are used as therapy animals in health-
or infection by resistant pathogens from been isolated in dogs associated with pet care facilities or nursing homes13. n
companion animals within the house-
hold due to their close interactions with
pets and the environment and also as Veterinarians play an important role in the education of pet
they are less likely to follow good hygiene owners in relation to zoonotic risk associated with resist-
practices and hand washing12. Pets can ant bacteria in companion animals1,5, even when dealing
become infected with resistant bacte- with clinically healthy pets5. Recommendations for infection
ria from human origin (anthroponosis) control practices when caring for pets are important in order to protect
such as MRSA and act as a reservoir in clients from potential zoonotic bacteria2.
the household and the veterinary clin-
Good hygiene practices should be followed, including when caring for healthy
ic12,14,20. Colonised or infected pets can
pets, as these could also act as carriers for resistant bacteria even in the ab-
also be a risk for the general public by
Figure 1 - Multidrug resis­tant bacteria in sence of clinical disease1,2. This is in order to prevent and limit the transmis-
contaminating the environment (e.g.
companion animals are an emerging public sion of zoonotic pathogens to humans and other animals in the household and
health is­sue that should not be overlooked. faeces and urine)4,5,14.
the contamination of the shared environment.

390 391
RECOMMENDATIONS

392
Nosocomial infections

393

RECOMMENDATIONS
How to prevent and deal with
R.24
nosocomial infections in
a veterinary practice? develop a culture where hygiene and
cleanliness are foremost.
most important measure to prevent
the spread of hospital-acquired in-
fections. Alcohol gels on uniforms
Sources of contamination include animals, and kennels can be quickly used af-
The prevention and control of nosoco- measures, fluids, tissues, bedding, kennels, floors, ter handling an animal, but are only
mial infections are based on: n high standards of staff training walls, tables, equipment, food and water. effective if hands are visibly clean.
n effective hand hygiene, and motivation, Hand touch sites are the most com- Practice design should therefore al-
n effective cleaning and disinfection, n effective surveillance, monly contaminated and important in low access to hand washing facili-
transmission. Hand washing is the single ties without having to touch anything.
RECOMMENDATIONS

RECOMMENDATIONS
n appropriate protective clothing, n effective protocols for managing

n high standards of clean surgery, patients with antimicrobial resistant


infections.
n effective isolation and barrier nursing

The main risk pathways for colonisa- guidance is available for veterinary
tion and infection with antimicrobial practices from a variety of sources (see
resistant bacteria are within veterinary further resources).
clinics (see Figure 1). These organisms
readily colonise healthcare environ-
Veterinary Medical
ments where they can be disseminated
staff environment
to vulnerable patients. These infections
are of great concern as they harm the
practice reputation, limit the procedures
that can be performed and increase
morbidity, mortality and the cost and
Animals
complexity of treatment. Improving hand
hygiene and infection control measures
have reduced colonisation rates in hu-
man hospitals. Effective infection con- Effective cleaning and disinfection is key to prevent nosocomial infections.
trol is a professional responsibility for
veterinary clinicians. For example, in
Practice
environment
Owners Effective surveillance
the UK this is a key part of the Royal Passive surveillance is the most practical use similar data to screen patients for
College of Veterinary Surgeons (RCVS) Figure 1 - Risk pathways for colonisation
and infection with antimicrobial resistant type of monitoring. Medical records and potential contagious or other risks on
Practice Standards Scheme and Guide laboratory data can be used to assess
bacteria in veterinary practice. admission.
to Professional Conduct. Infection control wound breakdowns, infection rates,
antibiotic sensitivity tests, changing pat- Active screening of patients, staff or the
Improving infection control measures terns of disease and in-patient status, environment is only indicated as part
Veterinary practices must develop in- infectious organisms (see box at the end etc. Systematic collection and analysis of an epidemiological investigation of a
structions and guidelines to reduce of the chapter). Everyone has a role in of this information allows early iden- specific outbreak. Active surveillance must
colonisation and dissemination of anti- effective biosecurity and infection con- tification of problems and facilitates have clear aims, a defined protocol and
microbial resistant bacteria and other trol and staff should work together to prompt action. Reception staff can also specific action in light of the findings.

394 395
R.24
How to prevent and deal with nosocomial
infections in a veterinary practice?

Table 1 - Key steps in effective infection control. Table 1 (continued)

• Clean and disinfect hands before and after touching animals or • Use extra protection for high risk cases; change between patients
Barrier
their surroundings (see Figure 2). gloves, aprons, masks, eye protection, etc. may be necessary for
nursing
• Train staff in effective hand washing and disinfection techniques contact with body fluids, lesions and other contaminated materials.
Hand hygiene (see Figures 3 and 4).
• Visibly soiled hands must be washed before using disinfectant gels. • Use a high standard of preparation, cleanliness and surgical skill.
Surgery
• Arms should be bare; avoid watches, jewellery and nails that See Prevention of surgical complications, p.258 for more details.
could interfere with cleaning.
• Train and encourage all staff to follow infection control guidelines.
RECOMMENDATIONS

RECOMMENDATIONS
• Gloving is not a substitute for hand washing and disinfection. Training • Adopt written infection control protocols.
• Wear gloves for clean and/or aseptic procedures and/or when • Appoint an infection control champion (or team).
there is increased risk of transmission of infectious organisms.
Gloves • Encourage clinical audit and review of infections and resistance
• Wash and/or disinfect hands before and after wearing gloves.
patterns.
• Remove gloves before touching equipment that is non-sterile or
not immediately involved in the procedure. Surveillance • Discuss results with your microbiology laboratory.
• Consider joining clinical surveillance programmes (e.g. SAVSNET
• Wear clean appropriate protective clothing at all times. in the UK).
• Change out of protective clothing when leaving the premises.
Protective • Long hair should be tied up and back when working.
clothing • Ties should not be worn.
• Excessive equipment, pockets and pouches should be avoided;
where necessary these should be cleaned and disinfected regularly.
• Equipment and surfaces must be thoroughly cleaned and
disinfected between patients; disinfectant wipes can be used if
surfaces are visibly clean.
After
• Stethoscopes should be cleaned and disinfected between patients. Before you 3
• Use approved detergents and disinfectants. touch me 1 touching me

• Cleaning should be performed according to strict rotas and


protocols - visual assessments are highly unreliable. After contact with
• Cleaning should be divided into daily, weekly and monthly tasks my body fluids 4
Cleaning and depending on the potential contamination and risk.
disinfection • Identify and separate clean and soiled items. Before carrying out a
• Dispose of clinical waste promptly and correctly. clean/aseptic procedure 2
• Avoid materials that can’t be cleaned in high risk sites – consider After touching my
waterproof keyboards or keyboard covers, laminated instructions surroundings 5
and posters, white boards and impervious seats in clinical areas.
• Clean leads, ropes, harnesses, collars, muzzles or rugs, etc.
should be allocated to each animal on admission; these should
remain with the animal during hospitalisation, must not to be Figure 2 - The key moments for hand hygiene (courtesy of the University of Edinburgh Royal [Dick]
shared and must be replaced if soiled. School of Veterinary Studies).

396 397
R.24
How to prevent and deal with nosocomial
infections in a veterinary practice?
RECOMMENDATIONS

RECOMMENDATIONS
Figure 3 - UK National Health Service guidance for effective hand washing (Crown Copyright 2007 Figure 4 - Effective hand disinfection – effective if hands are visibly clean (Crown Copyright 2007
283373 1p 1k; adapted from World Health Organisation Guidelines on Hand Hygiene in Healthcare). 283373 1p 1k; adapted from World Health Organisation Guidelines on Hand Hygiene in Healthcare).

398 399
R.24
How to prevent and deal with nosocomial
infections in a veterinary practice?

Managing patients with antimicrobial resistant


Managing patients with antimicrobial
infections resistant infections
Screening all cases prior to admission • antibiotic treatment within the previ-
is not usually feasible in most practices. ous 3 months,
Specific risk factors for Healthcare-As- • Admit known or suspected cases directly into a consultation room to avoid the
• non-healing wounds, waiting room.
sociated Infections (HAIs) and antibiotic
resistance include: • post-operative infections, • Take samples for culture as soon as possible, but treat all suspect cases as
RECOMMENDATIONS

RECOMMENDATIONS
• animals that have received one or more • nosocomial infections. n positive until culture results are available.
broad-spectrum antibiotic courses,
• Minimise movement and procedures; where possible schedule last in the day.
• animals with an on-going infection
• Discharging wounds should be covered with an impermeable dressing.
despite antibiotic treatment,
• Use trolleys to minimise contamination of corridors etc.
• Contaminated trolleys, rooms or corridors should be disinfected before further
use.
• Avoid contact between infected patients and other animals and staff.
• Use strict barrier nursing precautions and where necessary, isolation facilities.
• Pens/pencils, stethoscopes, thermometers etc. should be used with the affected
patient only and then disposed of or disinfected.
• Patients should be discharged as soon clinically fit. Samples should be taken
from appropriate sites to detect persistent colonisation (e.g. mucosal swabs
and/or faeces). The sites, type and frequency of culture should be addressed
Further resources on a case by case basis, following advice from clinical specialists and
• British Veterinary Association - www.bva.co.uk/public/documents/bva_antimicrobials_poster.pdf microbiologists where necessary.
• British Small Animal Veterinary Association - • If the animal remains colonised potential risks and precautions, including
www.bsava.com/Resources/PROTECT.aspx
hygiene, must be discussed with the owner; give clear written guidance.
www.bsava.com/Resources/MRSA.aspx
• British Equine Veterinary Association - www.beva.org.uk/useful-info/Vets/Guidance/AMR • Animals with persistent colonisation are best left to decolonise in the
• Responsible Use of Medicines in Agriculture Alliance (RUMA) - www.ruma.org.uk community; antimicrobial shampoos or wipes may be beneficial but may not
• Federation of European Companion Animal Veterinary Associations (FECAVA) - www.fecava.org be feasible, and the pros and cons of this approach should be discussed with
• International Society for Companion Animal Infectious Diseases (ISCAID) – www.iscaid.org
the owners.
• The Bella Moss Foundation - www.thebellamossfoundation.com • Antibiotics should be avoided, as these may facilitate persistent colonisation.
• Antibiotic treatment support materials and other resources - www.itsinfectious.co.uk • Active decolonisation of the household (including animals and humans) should
• Antibiotic Action and Antibiotic Guardian campaigns only be considered where necessary with the full consultation and cooperation
www.antibiotic-action.com and www.antibioticguardian.com
of medical healthcare services.
• SAVSNET - The Small Animal Veterinary Surveillance Network - www.savsnet.co.uk

400 401
RECOMMENDATIONS

RECOMMENDATIONS
Antimicrobial prophylaxis
for surgery and
critical care

402 403
How can infections be prevented
R.25
when using indwelling devices
(e.g. urinary catheter, IV catheter...)?

n Strict aseptic techniques of implantation.


n Prevention of patient interference.
n Shortest contact period as possible.

n Monitoring for clinical signs of infection.


RECOMMENDATIONS

RECOMMENDATIONS
All invasive devices provide open access by bacteria. In the right environment,
from the patient’s own microflora and these bacteria may be a source of infec-
environment to the body system. Even- tion, even if they are not pathogenic.
tually all these devices will be colonised

Implan­tation

© Hervé Brissot
The first rule when using an invasive de- contamination at the time of insertion.
vice is to adhere to strict aseptic tech- Operators should use gloves and/or
niques. The area to be treated needs to scrubbed/decontaminated hands (ster-
be clipped and the skin should be pre- ile gloves are mandatory for a central IV Figure 1 - An indwelling urinary catheter has been placed in this paraplegic mastiff. A soft Fo-
pared as for a surgical intervention with line). ley catheter has been placed aseptically and is connected to a collection bag to void the urinary
bladder. The bag is drained periodically. Ideally, it is placed lower than the body to increase gravity
scrubbing and application of an anti- If the device needs to stay in place, a drainage and prevent ascending contamination. Note that the collection bag is placed on an inco
septic solution. The mucosa (for urinary protective dressing is placed to limit sheet within a tray to avoid contact with the ward floor.
catheterisation) should be irrigated with ascending contamination. For critical
saline and diluted antiseptic solutions implants such as a central IV line, lo-
(povidone iodine 0.02%, chlorhexidine Regular flushing is advised for intrave- devices such as jugular catheters)
cal application of antibacterial oint-
diacetate 0.05%). nous catheters but not for bladder cath- for signs of local inflammation/in-
ment is recommended. For urinary
eters as this may cause a uretero-vesical fection, such as fever, local redness
Great care should be taken to avoid catheters, closed collection is set up.
reflux and ascending nephritis. at the point of insertion or a modi-
The patient should be assessed at least fied appearance of the drained fluids.
Handling and monitoring once daily (four times daily for critical
Once in place, implants should be han-
dled while wearing clean disposable
gloves or scrubbed/decontaminated hands Dealing with contamination
All exits should be kept capped unless Two problems may be observed with in- simply be due to inflammation sec-
continuous drainage is expected. Closed dwelling devices: phlebitis (IV catheter) ondary to the foreign material; there-
drainage units are recommended as they and cystitis (long-term catheterisation). fore, removal will resolve the problem.
prevent accumulation of ‘‘stagnant’’ or- The first rule when using an invasive device is Usually, removal of the IV catheter suf- Although urine contamination may be
ganic liquids (seroma, urine) within the to adhere to strict aseptic techniques. fices to resolve the problem and antibi- observed on cytology, antibiotic therapy
body which can favour bacterial growth. otics are rarely necessary. Cystitis may is not recommended unless there are

404 405
How can infections be prevented when using
R.25
indwelling devices (e.g. urinary catheter,
IV catheter...)?

clear clinical signs of infection. case of indwelling urinary catheters,


urinanalysis might be more relevant
If colonised, implants will be covered by
than culture of the tip of the catheter.
a biofilm produced by the bacteria, which
In cases of life-threatening infection,
will protect them from the immune system
broad-spectrum antibiotics against Gram+
and from the action of the antibiotics.
and Gram- may be considered empiri-
This is why treatment of an implant in-
cally until results are known. In critical
fection with antibiotics will only reach
cases, IV administration of ß-lactams
the bacterial overgrowth associated with
or first-generation cephalosporins is
the infection but no longer attached to the
RECOMMENDATIONS

RECOMMENDATIONS
indicated. In healthy patients, antibiotic
implant. It will never sterilise the focus of
treatment may be delayed until culture
infection. Therefore, infection will return
and sensitivity results are known. 1 2 3
as soon as treatment is discontinued and
the antibiotics used will select for more In cases where the implant cannot be
resistant bacteria. Eventually, mul- removed or changed, infection should
tiresistant bacteria will be selected. be treated for as short a time as possi-
Especially in critically ill patients, it is ble and with the least critical antibiotic
recommended to use the tip of the implant as possible to keep the therapeutic op-
for culture and sensitivity testing. In the tions open after removal of the implant. n

© Hervé Brissot
4 5 6

Figure 2 - Placement of an over-the-needle IV catheter.


1. The chosen vein is identified while the limb is restrained by an assistant (here a lateral
saphenous vein).
2. Wash hands before catheter placement (scrubbing or hydro-alcoholic hand rub).
3. Clip and prepare skin around the vein (scrubbing and application of an antiseptic solution).
4. Puncture and catheterise the vein.
5. Fix the catheter with adhesive tape.
6. Place a short extension set (T-port) to prevent direct action on the catheter that may increase
the risk of contamination. The entire system catheter-T-port is bandaged to only leave
access to the T-port. Catheters should be flushed with heparin saline when not used every
4 to 6 hours. Catheters should be changed if local inflammation/infection is suspected or as
a rule minimum every 3 to 5 days pending on hospital policy and patient condition.

If the device needs to stay in place, a protective dressing is placed to limit ascending contamination.

406 407
R.26
How can surgical infections
be prevented?
Table 1 - ASA (American Society of Anesthesiologists) score: assessment of the anaesthetic risk
of the patient.

Category Physical status Infectious risk


n Identification of patient risk factors and/or post-operative antibiotic
I Normal healthy patient 0 / no ABs needed
(see Table 1). treatment if needed). See also

Increasing risk
Prevention of surgical complications

of infection
II Patient with mild systemic disorder 0 / no ABs needed
n Identification of surgical risk factors (including peritonitis and abscesses),
(Altmeyer’s classification, surgical time, Patient with severe systemic
RECOMMENDATIONS

RECOMMENDATIONS
p.258. III + / consider preventive ABs
peri-operative hypothermia, delayed disorder
for enteral feeding; see Table 2). n Clean surgery <90 minutes and
without implant does not require Patient with severe systemic
IV ++ / use preventive ABs
n Good “surgical footprint”: protect antibiotic prophylaxis. disorder engaging survival
healthy tissue, limit surgical trauma
n When antibiotic prophylaxis is sci- Moribond, not expected to ++(+) / use preventive and
and help restore normal function and V
entifically indicated, respect the 5 survive without surgery postoperative ABs
biology.
rules of antibiotic prophylaxis (see
n Quality of non-surgical treatment box The 5 rules of antibiotic prophy-
(wound care, antibiotic prophylaxis laxis p.411). sites will increase the risk of infections
that may be a challenge to treat with an-
Identification of patient and surgical risk factors tibiotics.
Post-operative infection (POI) is the result operative antibiotics. Post-operatively, In surgery, hypothermia and operating
of a favourable environment for bacte- patients should not be starved as this will time are closely linked to each other.
ria to grow and to overcome local host decrease the effectiveness of the immune Studies showed that the risks of in-
response. There are multiple factors in- system and may favour the translocation fection in clean surgeries increased by
volved in surgical infection. 30% every hour.
of bacteria from the intestinal lumen
Patient status is important, e.g. immune into the general circulation. Therefore, Clipping just before the surgery, redu-
deficiency, poor body condition, age, en- the intestinal tract should be used even cing air circulation in theatres during
docrine disorders (especially diabetes) after gastro-intestinal surgery. If re- surgeries and taking active measures
and gender–male animals have an in- quired, a tube-feeding strategy (naso- to maintain normothermia may help in
creased risk of POI. oesophageal tube or oesophagostomy, limiting the infection risks.
Disinfection of the site of catheter insertion
Surgical risk factors: Altmeyer’s clas- gastrostomy or jejunostomy tubes) should is an essential point in limiting the risk of
sification (Table 2) is routinely used to be considered during surgery and post- phlebitis.
identify patients needing pre- or post- operatively.
Why and when
Good surgical footprint Antibiotic prophylaxis aims to achieve an will be readily deactivated or killed by
The ‘‘surgical footprint’’ represents the restore normal function and biology. The active concentration (above the MIC) in the antibiotics. However, antibiotics are
ability of the surgeon to protect healthy accumulation of fluid, dead space or ne- the tissue during surgery. Any bacteria only needed at the time of the surgery
tissue, to limit surgical trauma and to help crotic/devitalised tissues in the surgical getting into contact with the surgical site and should be discontinued immediately

408 409
R.26
How can surgical infections be prevented?

after surgery or within the following hours. The most likely bacteria to be encoun-
Table 2 - Altmeyer’s classification and infectious risk associated with the type of surgical procedure. This protocol is indicated for long clean tered are commensals from the skin
This classification aims to help surgeons in the assessment of the risk for postoperative infection
and clean contaminated procedures (see (mainly Gram-positive: Staphylococcus
and the rational use of antibiotics. The antibiotic choice is based on the bacteria to be likely present
in the surgical field (see Prevention of surgical complications (including peritonitis and abscesses), Altmeyer’s classification). Clean surge- spp.) and possibly from the environment
p.258). ry <90 min and without an implant does (Gram-negative: E.coli).
not require antibiotic prophylaxis.
Classification Type Antibiotic treatment

Non traumatic. No antibiotics. Which antibiotics?


Antibiotic prophylaxis may ß-lactams and first generation cepha- clean orthopaedic surgery decreased
RECOMMENDATIONS

RECOMMENDATIONS
Non inflammatory.
be performed in case losporins are generally recommended post-operative infection. He also showed
Clean No breach of asepsis, of clean orthopaedic for antibiotic prophylaxis. They should that there was no benefit of cefazo-
procedure shorter procedures involving be injected IV 30 to 60 minutes before lin over penicillin G regarding the de-
than 90 minutes. implants. the initial incision to ensure that active creased risk of complications. In view of
Clean, longer than 90 minutes. concentration will be found locally at the likely bacteria (Staphylococcus spp.)
Minor opening without Targeted antibiotic the time of surgery. As the tissue able to contaminate the surgical site,
spillage of the respiratory, prophylaxis. concentration should remain higher narrow-spectrum antibiotics should be
Clean-contaminated than the MIC during the time of possible used to limit selection for resistance
urogenital, biliary or intestinal No post-operative
tracts. antibiotics. contamination, repeated administration and to keep therapeutic options open.
Minor breach of asepsis. is required: every 90 to 120 minutes. Rational for antibiotic choice is dis-
Cephalosporins are generally adminis- cussed in Prevention of surgical com-
Traumatic wound tered every 90 minutes in case of or- plications (including peritonitis and abs-
(less than 4 to 6 hours). Antibiotic prophylaxis and
thopaedic procedures. Whittem et al7 cesses), p.258. n
post-operative antibiotics
Major opening of respiratory, showed that antibiotic prophylaxis for
(short duration).
urogenital, biliary or intestinal
Contaminated
tracts with or without obvious
infected content.
Possibly, sampling for The 5 rules of antibiotic prophylaxis
culture and sensitivity
Controlled spillage of the testing. • Scientifically indicated (not a clean procedure <90 min without implants)
tract content. • Targeted (monotherapy toward the bacteria most likely to contaminate the surgical site)
Surgical site with pus. • Bactericidal
Surgical site with faecal Pre- and post-operative • Appropriate tissue concentration (above the MIC) at the time of surgery; this concen-
contamination, foreign antibiotics (long term). tration should be maintained until the end of the procedure*
Dirty material, devitalized/necrotic Recommend sampling • Administer IV 30 to 60 minutes prior to incision; discontinue 24 hours after surgery.
tissue. for culture and sensitivity First-generation cephalosporins are commonly used in veterinary practice (e.g. cefazo-
Traumatic wound testing. lin or cefalexin 20mg/kg). The risk of infection is lower for soft tissue procedures (where
(older than 6 hours). drugs will be administered every 2 to 3 hours) compared to orthopaedic surgery where
a higher administration frequency (e.g. every 90 minutes) and dosage (30 mg/kg) are
generally recommended.
*The drug should be re-administered after a period equivalent to one to two times the drug’s half-life.
Ex: cefazolin IV has a half-life of 1h; if used for antibiotic prophylaxis, it should be re-injected every 2h.

410 411
Am I doing it right? Five tools to
R.27
assess my surgical site infection
prevention protocol. Table 1 - Definition of Surgical Site Infection (SSI) 6.

Classification Criteria

Within 30 days.
1. Definition of surgical site infections 4. Up-to-date and accurate re-
Skin / subcutis.
(see Table 1). cords for clinical cases, antibio-
1 or more of the following:
tic use, cleaning and training in - Pus.
2. Systematic assessment of all surgi-
infection control. Superficial SSI - Bacteria on cytology.
cal wounds at suture removal.
RECOMMENDATIONS

RECOMMENDATIONS
5. Effective clinical audit. - Local signs of inflammation (heat, redness, pain)
3. Recording of all bacterial culture and justifying surgical re-exploration. This has to be
antibiotic susceptibility test results. classified as infection unless culture/sensitivity
is negative.
Veterinary practices must be able to as- to review data and make recommenda-
sess the effectiveness of their antibiotic tions on a regular and scheduled basis. Within 30 days, up to a year if implants in situ.
stewardship programmes and infection Soft tissues deeper than the incision.
• Assessment of surgical site infec- 1 or more of the following:
control measures. This facilitates early tions (SSIs) is an easy and important set - Pus.
detection of problems allowing prompt of data to record. However, there is no Deep SSI - Spontaneous dehiscence or surgical re-exploration
and effective action. Practices can then widely accepted definition or classifi- due to suspected infection unless culture/sensitivity
modify their protocols to better suit their cation for SSIs and therefore practices is negative.
structure, facilities and caseload. Good must adopt their own criteria. Turk et - Abscess or any evidence of infection on
record keeping and effective use of cli- al.1 proposed a thorough definition diffe- imaging/history.
nical audit are a professional responsi- rentiating superficial, deep and organ/
bility and some hospitals have included space SSIs with assessment done at Within 30 days, up to a year if implants in situ.
them in their Practice Standard Scheme 1 and 12 months postoperatively. This Any part of the body that has not been opened/manipulated
(e.g. UK Royal College of Veterinary Sur- provides an adequate start for a practice Organ or space SSI during surgery.
geons). to develop its own protocol. Abscess or any evidence of infection on examination,
exploration or imaging/history.
This approach requires careful planning, • Besides SSIs, it is also important to
recording and review of all available and record any other possibly infectious
appropriate data. No system will work process observed during or just after
in each situation and practices will have hospitalization. This will allow detection • The results of bacterial culture and resistance among the hospital popula-
to develop their own arrangements ap- of any non-surgical hospital-acquired antibiotic susceptibility tests should tion. This can help inform good clinical
propriate to their size and activity. Ne- problems such as kennel cough, der- be recorded and periodically reviewed. practice and antimicrobial stewardship.
vertheless, a properly planned and exe- matophytosis, MRSA, MRSP or E. coli Special attention should be given to an- • Regular and routine reviews of the
cuted system does not need to be overly colonisation, Salmonella etc. Prompt timicrobial resistant, post-operative and data by appropriate staff should be esta-
complicated or time consuming. Indivi- sampling of animals with post-operative hospital-acquired infections. However, blished. The frequency of this will depend
dual members of staff should keep their and/or hospital-acquired coughing, skin monitoring resistance trends provides on the importance of the activity, type of
records up to date and computerised re- lesions, diarrhoea and/or urinary tract useful information for choosing effective data and speed of response that would
cord keeping will facilitate data capture. monitoring and sampling of animals after antimicrobials: the prevalence of diffe- be required. Reviews in important areas
A small team should therefore be able discharge from the veterinary practice. rent organisms and the frequency of should be done not less than monthly,

412 413
Am I doing it right? Five tools to assess my
R.27
surgical site infection prevention protocol.

but reviews in less critical areas and/or


reviews of trends could be done every
Recommendations by
6-12 months. It is important to review clinical audit group Clinical practice
the data against comparable figures to
provide a benchmark for the location
and type of practice. Benchmark figures
Review of data by Record keeping and
may be earlier data from the same prac- clinical audit group data collection
tice, regional information from clinical
audit and surveillance schemes and/or
RECOMMENDATIONS

RECOMMENDATIONS
data from the veterinary literature.
• All staff should be trained and encou- Antimicrobial Clinical Post-operative Morbidity and
raged to record data routinely and par- susceptibility tests outcomes infections mortality

© Hervé Brissot
ticipate in clinical audit. They should be
reassured that this is not a way to appor-
tion blame, but is to identify and correct Figure 2 - Example of a clinical audit procedure.
problems to improve patient care. These The exact nature of the data recorded, reporting procedure, reviews and action, as well as the
‘‘no blame’’ approaches have greatly make-up of the clinical audit group, will depend on the type, size and caseload of the practice.
Figure 1 - This dog had an extra-articular
enhanced reporting and outcomes in stabilisation of his stifle after cranial cru-
veterinary and medical healthcare, food ciate ligament rupture. He presented 3
safety, engineering and a wide range of weeks later with a deep SSI. In this case,
sampling the pus is not relevant; sampling
other areas. should be performed on the deep sutures.
• Clinical audit should identify precise
areas for improvement. Overly complex • Active surveillance measures are more
and ambitious aims become overwhel- expensive, time consuming, and may
ming and often defeat their objectives. be misleading. Active targeting of staff
People find it much easier to focus on and work areas can lead to a defensive
small-scale, specific and achievable ‘‘blame-centred’’ culture that discour-
aims. In time, these can lead to profound ages involvement in clinical audit and
improvements in practice. This has been infection control. Nevertheless, spe-
demonstrated in a very wide range of cific problems highlighted by passive
fields including healthcare, science, en- surveillance may require more active
gineering, education and sports. investigation of patients, wounds, ma-
• Passive surveillance for clinical audit terial, equipment and, possibly, staff to
and infection control are fairly straight determine the cause of the infections.
forward and inexpensive procedures. Active surveillance should be carefully
They facilitate the “no-blame” approach, planned to answer a precise problem,
which encourages a committed and and avoid the risks of appearing to ap- Surgical site infection prevention must follow a strict procedure.
supportive culture (Figure 3). portion blame. n

414 415
Am I doing it right? Five tools to assess my
R.27
surgical site infection prevention protocol.

Regular review of bacterial culture and


antimicrobial sensitivity test results

Five cases of Burkholderia cepacia in one month


RECOMMENDATIONS

RECOMMENDATIONS
Unusual pathogen in animals

Investigation of common links between the cases


Recommendations
All of the cases had undergone bronchoscopy
to pet owners

Burkholderia cepacia cultured from flexible bronchoscope

Flexible bronchoscopy suspended


Review of hygiene and cleaning procedures
Records showed that correct procedures were followed
after each bronchoscopy

Burkholderia cepacia cultured from the automated


bronchoscope cleaning bath
Further tests revealed a fault in the cleaning cycle

Figure 3 - Real-life example of passive surveillance and clinical audit in veterinary practice.
In this (real) example, passive surveillance quickly identified an unusual cluster of infections. The
focused investigation resolved the problem within five days, minimising the impact on clinical
services and the risk to patients. Good record keeping and a “no blame” approach lead to a rapid
resolution.

416 417
What are the recommendations
R.28
and advice that can be given to
the pet owner?

Veterinarians have an important role (human drugs), other animals or


in the education of pet owners. It is different conditions,
therefore essential to allocate time • follow the instructions provided by
during the consultation to explain the the veterinarian, including:
RECOMMENDATIONS

RECOMMENDATIONS
treatment plan to the client and be
- administration of the recommend-
ready to answer any questions they
ed dose and frequency,
might have regarding the therapeutic
course and the condition of their ani- - completion of the course of anti-
mal; microbial therapy prescribed - this
should not be discontinued unless
n Recommendations for pet owners
stated otherwise by the veterinarian,
are similar to those observed by human
patients. Where possible pet owners - report to the veterinarian any ad-
should: verse effects or anomalies observed
One of the key recommendations for owners is to give the appropriate dose and frequency of an
during the treatment course, anti-infective treatment.
• only undertake antimicrobial treat-
ment under prescription from a vete- - attend the follow-up consulta-
rinarian, tions, as this will allow the veteri- Poor compliance to prescribed therapy and welfare due to the risk of relapse
narian to assess the effectiveness of can lead to treatment failure and recur- and lead to the occurrence of antimicro-
• not continue treatment without ve- the therapy prescribed.
terinary advice, rence of infectious conditions and can bial resistance. The veterinarian should
n Veterinarians should: therefore compromise animal health therefore stress the importance of fin-
• not treat the same condition or
and welfare1 and increase veterinary ishing the prescribed course of therapy
another condition with the same drugs • make arrangements to follow-up costs to pet owners2,14. Furthermore, it to pet owners. In the recommendations
without veterinary advice, the progress of the animal during can also lead to distress for pet owners made to pet owners, the veterinarian
• dispose of unused medicines cor- therapy and re-assess the treatment due to the prolonged suffering of their should also discuss the possibility of
rectly and not re-use without veteri- plan; this could be through a phone pets, particularly when in the presence occurrence of adverse reactions, as this
nary advice, call or a consultation. For the latter, of untreatable infections caused by mul- may discourage the client from complying
it is recommended to remind the pet tidrug resistant pathogens2.
• not purchase antimicrobials over the with the prescribed course of therapy
owner (letter, phone call, SMS...),
counter (including those purchased Pet owners should be discouraged from due to the perceived risk to the ani-
via the internet without a prescription) • remind pet owners to follow good stopping the antimicrobial course, as- mals health and welfare. The pet owner
or use leftover antimicrobials that were hygiene and infection control prac- suming that because an animal appears should be encouraged to seek veteri-
originally prescribed for themselves tices when caring for their sick pet. to be getting better, it is cured. It should nary advice in the presence of adverse
be explained to them that early disconti- reactions in order to allow revision
nuation of antimicrobial therapy, even in of the therapeutic plan and possible
the absence of clinical signs, may have a change to a more suitable and effec-
negative impact on their animal’s health tive antimicrobial therapy if required.

418 419
What are the recommendations and
R.28
advice that can be given to the pet owner?

Underdosing, inadequate frequency of the presence of treatment failure, the


dosing or duration of therapy can result veterinarian should investigate the po-
in antimicrobial resistance through se- tential causes for this occurrence. Lack
lective pressure upon commensal and of compliance is a common cause for
pathogenic bacteria1,6. This may result treatment failure and recurrence. Good
in colonisation and infection of com- communication with the pet owner is es-
panion animals with resistant strains sential to establish a good relationship
which may compromise animal health of trust with clients in order to ensure
and welfare3. This can pose a zoonotic compliance10. Poor communication of
RECOMMENDATIONS

RECOMMENDATIONS
risk to both pet owners and veterinary zoonotic risks by veterinarians has been
staff8,9,12. Transmission of zoonotic resis- previously reported as a relevant issue in
tant pathogens such as MRSA from col- practice by pet owners13. The veterina-
onised and/or infected pets through col- rian should allocate time to discuss the
onisation of humans and other animals prescribed therapy during consultation11
and contamination of the environment and the potential zoonotic risks of resis-
within the household can occur. This is tant bacteria. This is particularly impor-
also true for the horizontal transfer of tant when dealing with client pressure
resistant genetic determinants between for antimicrobial prescriptions or deal-
resistant pathogens and environmental ing with possible non-compliance.
bacterial populations and human gut Follow-up of cases, either through
flora4,8. consultation or via the phone will allow
the veterinarian to assess the effective-
It is important that pet owners follow the
ness of the treatment and the progres-
veterinarian’s advice in order to prevent
sion of the condition of the animal. The
self-medication with either licensed
veterinarian will then be able to advise
veterinary or human antimicrobial pro-
the pet owner if the therapy should be
ducts, as this may compromise the effi-
stopped, changed or continued, depen-
cacy and safety of treated animals and
ding on the progression of the condition
lead to the occurrence of antimicrobial
affecting the animal. Failure to attend
resistance. Off-label use of antimicro-
the follow-up consultation may result
bials should only be conducted under
in treatment failure and recurrence of
the supervision and recommendation of the condition. If the failure is due to a
the veterinarian if no licensed veterina- suspected occurrence of resistance, the
ry drugs are available, as stated by the veterinarian should consider sampling
Cascade principle5. the site of infection and carry out anti-
Follow-up consultations are important microbial susceptibility testing (AST)3,7.
as they allow the veterinarian to re-as- This could have serious animal health
sess the clinical condition of the animal and welfare implications and additional
and the effectiveness of the therapy. In costs for the animal owners. n

420 421
What are the recommendations and advice
R.29
for owners of premises where pets are kept
The close proximity of animals sharing and therefore make it more prone to
in groups (breeders, kennels, catteries…)? the same physical space, sometimes infection and colonisation by bacteria
kept at high-density levels leading to and other pathogens3. Therefore, it is
overcrowding, can facilitate the spread important to put effort into the preven-
of infectious diseases in susceptible tion of infectious diseases commonly
n Breeders, kennels and catteries • administer at the recommend- populations. Particularly in premises observed in animals kept in these sys-
should follow similar recommenda- ed dose and frequency, where there is the mixing of animals tems. Development of infection control
tions for pet owners with slight modi- • complete the course of antimicrobi- from different origins (e.g. catteries protocols and animal health plans are
fications: al therapy prescribed; this should not and kennels), unknown health and vac- essential to prevent and control disease
RECOMMENDATIONS

RECOMMENDATIONS
• antimicrobial treatment of their be stopped unless otherwise stated cination status and large turnover (e.g. in environments where risk of infectious
animals should only be undertaken by the veterinarian, animal shelters), the risk of introduc- diseases is high12. Good hygiene should
under veterinary prescription and su- • report to their veterinarian any ad- tion and spread of infectious diseases be observed by staff to prevent the
pervision, verse effects or anomalies observed is higher than in households with only spread of infectious diseases. Training
• individuals should not purchase an- during the treatment course, one pet1,11. Furthermore, the keeping of programs should be in place to ensure
timicrobials over the counter (inclu- • attend the follow-up consultations large groups can also result in stress for responsible antimicrobial use and good
ding those purchased via the internet or agree to follow-up phone calls or the affected animals which may com- hygiene practices by staff (see Table 1).
without a prescription) or use leftover emails, as these will allow the veter- promise the animal’s immune system
antimicrobials that were originally inarian to assess the effectiveness of
prescribed for themselves (human the therapy prescribed,
drugs), other animals or different
• carry out vaccination and worming
conditions, Table 1 - Recommendations and advice regarding zootechnical measures in canine and feline bree-
programmes in order to prevent the ding establishments.
• develop and implement animal occurrence and spread of infectious
health schemes and infection control diseases in the animals under their Zootechnical measures
protocols in collaboration with their care,
veterinarians, - Premises layout (quarantine, hospital, infirmary, nursery...).
• isolate and quarantine suspect or Premises - Cleaning, disinfection and depopulation protocol.
• train staff to follow good hygiene diseased animals to avoid spread of
and infection control practices, - Incoming patient management (state of health,
disease across the animal population
vaccinations, testing, adaptation to microbial
• Educate staff to raise awareness and treat on a case-by-case basis,
environment…).
regarding potential zoonotic risks. • avoid mass prophylactic or meta- - Short term management of suspect or sick animals:
phylactic treatment of animals with Individuals identification, isolation, veterinary care.
n Breeders, kennel and cattery staff antimicrobials, - Long term management of suspect or sick animals in
should follow the instructions provi- • good hygiene practices (cleaning reproduction: artificial insemination, withdrawal from
ded by the veterinarian, including: and disinfection, hand hygiene...). breeding.
- Continuous education about: respect of isolation,
When dealing with breeding centres, also economic considerations to take compliance with antibiotic treatment (doses, duration,
catteries or kennels, the veterinarian is into account, due to the monetary value Staff veterinary control).
dealing with population medicine, but of the animals (e.g. purebred breeding - Continuous education about: zoonosis, respect of usual
must still care for the health and wel- animals)7 and the potential loss of bu- and reinforced hygiene measures (gloves, masks...).
fare of the individual animal. There are siness (e.g. catteries and kennels).

422 423
R.29 What are the recommendations and advice for
owners of premises where pets are kept in groups
(breeders, kennels, catteries…)?

Cleaning and disinfection of premises of animals is high13. Animals should be


moved into empty cages or held by staff
clean the floors in areas with animals, as
these tend to spread pathogens around.
Disease transmission in shelters and • sanitation (e.g. application of a chemi- while their cage is being cleaned and di- Instead, hard bristle brushes with dis-
kennels often occurs through direct cal substance to reduce bacterial conta- sinfected. Mops should not be used to infectants should be used. Good hand
contact with infected animals, aerosols mination),
and fomites13. Cleaning and disinfec- • disinfection (e.g. use of a licensed di- Table 2 - Efficacy of disinfectants in known small animal pathogens21.
tion of the environment is important to sinfectant that will kill the viruses and
contain spread of disease; only licensed bacteria, but not spore-forming orga- Pathogens
products for the effect required should nisms), and

enveloped viruses

enveloped viruses
RECOMMENDATIONS

RECOMMENDATIONS
be used in the premises1,3. Breeding

Gram-negative
• sterilisation (e.g. will kill all viruses

Gram-positive
Categories Examples

Mycobacteria
centres, kennels and catteries should

Envelopped
and bacteria, including spore-forming

Large non
bacteria

bacteria
design and implement protocols for

viruses

Spores
organisms)13.

Small

Fungi
cleaning and disinfection of their prem-
Good cleaning and disinfection of equip-
ises in order to ensure the protection of
ment and surfaces and following good + + +
both animal and human health19. Acid Acetic acid, citric acid, lactic acid. + + - + -
hand hygiene should be practised at - - -
There are four levels of cleaning in all times. Cleaning and disinfection of
group-housed environments: equipment and facilities should be per- + + + +
Alcohols Ethanol, isopropagol, methanol. + + + + - - - -
• physical cleaning (e.g. removal of or- formed daily and more frequently in pre-
ganic materials and waste from the en- mises where occurrence of infectious Glutaraldehyde, formaldehyde,
vironment), diseases is common or where turnover Aldehydes
orthophtalaldehyde.
+ + - + + + + +

Sodium hydroxide (caustic soda),


Alkalis calcium hydroxide (slaked lime), + + + + + + + +
- -
sodium carbonate, ammonium hydroxyde.

Biguanides Chorhexidine diacetate and gluconate. + + - + + + + -


- - - -
Chlorine Sodium hypochlorite (bleach, Clorox),
releasing calcium hypochlorite, + + + + + + + +
-
agent chlorine dioxide.
Iodine solutions (tintures) or iodophors
Iodine + + +
Iodophors
(complex of iodine with neutral polymers), + + + + - - + -
such as povidone iodine.
Hydrogen peroxide, accelerated hydrogen
Oxydizing + +
agents
peroxide, peroxyacetic acid, + + + + + + - -
peroxymonosullfate.

Phenolic Various phenols (2-phenyIphenol, benzyl + + +


compounds phenol, 4-chloro-3,5-dimethyl phenol...). + + + - - - + -
Quaternary Various ammonium salts (benzalkonium
The risk of introduc­tion and spread of infectious diseases among group-housed animals is higher than in ammonium chloride, benzethonium chloride, + + + + - - + -
- - -
households with only one pet. compounds cetalkonium chloride...).

424 425
R.29 What are the recommendations and advice for
owners of premises where pets are kept in groups
(breeders, kennels, catteries…)?

hygiene should be promoted amongst reduction of environmental levels of re-


the staff, volunteers and visitors; hand sistant bacteria such as Clostridium dif- Table 3 - Common infectious diseases in dogs and cats housed in group conditions, adapted from
WSAVA23.
sanitizers and hand washing facilities ficile and VRE, that can pose a serious
should be made available throughout risk for both animal and public health3. System Dogs Cats
the premises. Footbaths with approved Formaldehyde, bleach (sodium hypochlo-
disinfectants may also be required for Canine Upper Respiratory Disease
rite) at 1:32 dilution, quaternary ammo-
disease control purposes when out- ‘‘Kennel cough’’ (multifactorial- Feline Upper Respiratory Disease
nium compounds (note that some may
breaks occur13. Staff involved in the Canine Herpes virus, Canine (e.g. Feline Rhinotracheitis, Feline
not be effective in destroying parvo- Distemper virus, Canine Calicivirus)
cleaning and disinfection of premises viruses)13, peracetic acid or sodium pe- Respiratory
RECOMMENDATIONS

RECOMMENDATIONS
should move from healthy to sick areas Parainfluenza virus, Bordetella bronchiseptica
roxide have also been recommended for Canine Adenovirus virus type 2, Chlamydophila felis
to avoid the spreading of disease13. use in breeding premises, kennels, cat- Bordetella bronchiseptica, Mycoplasma spp.
Moist heat treatment (> 60°C) can be teries and animal shelters. These dis- Mycoplasma spp.)
used to sterilise equipment in close infectants are effective against viruses
contact with animals (towels and blan- that can survive in the environment (e.g. Canine Distemper
kets, feeding and water bowls). These canine and feline parvoviruses) that are (Canine Distemper virus)
measures are essential to control and often complicated by secondary bacte- Infectious Canine Hepatitis Feline Panleukopenia (FP)
prevent environmental dissemination rial infections (Table 2)23. It is important (Canine Adenovirus type-1) Feline Enteric Coronavirus (FECV)
Canine Parvovirosis (CP) Salmonellosis
of multidrug resistant pathogens such to adhere to the contact times recom- Gastrointestinal Canine Coronavirus Campylobacteriosis
as MRSA3. Ultraviolet light devices have mended for disinfectants in order for
Salmonellosis Protozoa (Cryptosporidium felis,
also been found to be relevant in the these to be effective13. Campylobacteriosis C parvum)
Protozoa (Giardia lamblia,
Vaccination Cryptosporidium parvum)
Adoption of animal health schemes is where companion animals are housed Gastrointestinal, Clostridium difficile Clostridium difficile
key in preventing disease introduction in groups, vaccination should be pro- opportunistic
and spread. Most infectious diseases moted not only for prevention but also
occurring in group-housed animals are for disease control in the presence or
viruses affecting the respiratory tract. suspicion of an outbreak1,11. Vaccination
In animal shelters, upper respiratory vaccination status of animals is often and catteries should require core vacci-
contributes both to the protection of the
disease and ‘kennel cough’ are the unknown due to the potential risk of nation of animals under their care as a
individual animal but also of the popu-
most common syndromes observed. infectious diseases, already mentioned precondition for boarding11 (see Table 4).
lation, through the effect of herd immu-
The most common infectious diseases above11. Owners of boarding kennels
nity. In this case, vaccination provides in-
in group-housed dogs and cats are direct protection of a large proportion of
shown in Table 3. Animals affected by individuals (non-immune) to infectious
viral infections are more susceptible to disease from susceptible individuals
secondary opportunistic bacterial infec- (e.g. non-vaccinated) within a given pop-
tions. ulation23. Vaccination programs should
Vaccination can reduce the burden of be developed as part of the health man-
disease and therefore of antimicrobial agement programs of shelter kennels
use in companion animals. In premises and catteries, where the health and

426 427
R.29 What are the recommendations and advice for
owners of premises where pets are kept in groups
(breeders, kennels, catteries…)?

disease or diarrhoea due to stress and


Table 4 - Core vaccinations recommended for dogs and cats housed in group conditions23. shed the pathogens in the environment.
Dogs Cats Isolation of diseased animals is impor-
tant to prevent the spread of disease
Canine Distemper virus (CDV) Feline (panleukopenia) parvovirus (FPV)
and to allow treatment of severely af-
Canine Adenovirus type-1 (CAV-1) and fected individual animals; for this pur-
Feline calicivirus (FCV)
Canine Adenovirus type-2 (CAV-2) pose, the shelter or kennel should have
appropriate isolation facilities14.
Canine Parvovirus type-2 (CPV-2) Feline herpes virus-1 (FHV-1)
RECOMMENDATIONS

RECOMMENDATIONS
Rabies virus* Rabies virus*
*Only in countries where rabies is endemic and poses an animal and public health issue.
Note: Bordetella bronchiseptica may be indicated in some shelters to be used as part of the core vaccination.

Quarantine of new arriving animals and


Animal shelters may also consider the canine Lyme disease, if the risk of expo- isolation of diseased animals are recom-
use of “non-core” vaccines, e.g. against sure is high (see Table 5)12. mended to prevent the introduction and the
Feline Leukaemia Virus (FeLV), and spread of disease.

Table 5 - Non-core vaccinations recommended for dogs and cats3. Use of antimicrobials
Dogs Cats Prophylactic and metaphylactic use of et al.16, no impact was observed on neo-
antimicrobials as the main means of natal mortality in treated animals.
Bordetella bronchiseptica* disease prevention in breeding, cat- A Belgian study found that healthy cats
± (Canine Parainfluenza virus Bordetella bronchiseptica* teries and shelter facilities should be
and/or Canine Adenovirus-2) kept in catteries had higher levels of
discouraged as it may lead to the emer- carriage of resistant indicator enteric
Lyme borreliosis (Borrelia burgdorferi) Feline Leukaemia Virus (FeLV) gence and spread of resistant bacteria bacteria (i.e. 33.3% of Escherichia coli,
Leptospirosis (e.g. Leptospira canicola, and resistance genes19. Prophylactic use 92.3% of Enterococcus faecalis and 56%
L. icterohaemorrhagiae, L. grippotyphosa, Chlamydia psittacci of antimicrobials at parturition in breed- of Streptococcus canis isolates) com-
L. pomona) ing kennels has been associated with pared to cats kept as single pets (15.8%,
the emergence of multidrug resistance 66.7% and 22.2%, respectively)17. This
* Bordetella bronchiseptica may be indicated in some shelters to be used as part of the core vaccination.
in Gram-positive bacteria in treated study underlined the potential role of
bitches16. Antimicrobials are routinely the shared environment, group hous-
used in breeding kennels in bitches, in ing17, animal density9 and widespread
order to reduce stillbirths and neonatal use of antimicrobials in particular age
Quarantine and isolation morbidity and mortality due to transfer groups (e.g. kittens) in the transmission
Quarantine is recommended for new the animal population23. For example, new of pathogens (e.g. Staphylococcus spp., of resistant bacteria17. ESBLs have also
animals arriving at animal shelters, due cats in shelters with asymptomatic, sub- Streptococcus spp. and Escherichia coli) been isolated in dead, sick and healthy
to unknown health status of the animals clinical infections may be disease car- via the genital tract and through lacta- dogs and cats privately owned or held in
and the risk of introducing disease into riers and can develop upper respiratory tion18. However, in the study by Milani kennels in a survey conducted in Rome9.

428 429
R.29 What are the recommendations and advice for
owners of premises where pets are kept in groups
(breeders, kennels, catteries…)?

Furthermore, community-acquired strains


commonly observed in humans were
management of future cases in affect-
ed litters. Post-mortem examination of
Zoonotic risk for animal owners and staff
also isolated in dogs in the same study deceased animals in an affected litter Individuals working in kennels, catteries DT104 was reported in the USA amongst
(e.g. SHV-12-positive Escherichia coli)9. may also help to reach a diagnosis and and breeding facilities may also be at animal shelter staff and diseased cats
aid in the disease management on the risk of occupational infections caused with subsequent spread into humans in
Colonisation with a human clone of MRSA
premises. Oral antimicrobials may not by resistant pathogens. An outbreak of the close community via adopted pets
(EMRSA-15) has also been reported in
always be recommended in neonates gastrointestinal infection due to multi- from the same shelter and secondary
7.8% of clinically healthy dogs recovered
and young animals due to the potential drug resistant Salmonella typhimurium human-to-human transmission22. n
in a shelter kennel in the Southeast of
England in a recent study by Loeffler et disruption of the development of the gut
RECOMMENDATIONS

RECOMMENDATIONS
al.15, at levels higher than usually obser- flora20.
ved at community level. Nevertheless, In animals that have received colostrum,
most colonisation was only transient infections may occur at 5-6 weeks of age
and transmission was not sustained in when passive immunity from the mother
the shelter environment probably due to has waned. In young animals, diarrhoea
implementation of effective cleaning and is rarely due to bacterial infections and
disinfection protocols15. therefore antibiotic therapy is rarely
Common conditions observed in kennels required; protozoal and parasitic infec-
include the Canine Infectious Respirato- tions are more common20. Empirical
ry Disease Complex (CIRDC) also known worming of kittens and puppies is usu-
as kennel cough that is often caused by ally recommended12. Upper respirato-
multiple viral and bacterial pathogens ry tract infections caused by Bordetella
(e.g. Bordetella bronchiseptica, Strep- bronchiseptica can occur and can be
tococcus zooepidemicus). S. zooepide- fatal particularly in neonates; in old-
micus can harbour resistance, often to er kittens mixed respiratory infections
doxycycline and can cause serious dis- are common20 (for therapeutic options,
ease in both pets and humans10. see Feline rhinitis and tracheobronchi-
Neonate animals in breeding centres tis, p.96). Viral infections through verti-
can be susceptible to bacterial infec- cal transmission from the dam may be
tions if they have a poor passive immu- observed; in kittens, Feline Immunodefi-
nity due to either insufficient colostrum ciency Virus (FIV), Feline Leukaemia Vi-
uptake or low antibodies (lack of expo- rus (FeLV), Feline Infectious Peritonitis
sure or compromised immune status) (FIP), Feline Parvovirus (causative agent
Disease transmission in shelters and kennels often occurs through direct contact with infected animals,
in the bitch or queen. Culture and AST for Feline Panleukopenia and Feline In- aerosols and fomites.
may not be useful in individual cases fectious Enteritis) and in puppies, Ca-
as very young animals may die before a nine Herpes virus and Canine Distem-
diagnosis is obtained but can aid in the per virus may occur20.

430 431
Part 3
SYNOPSIS
SYNOPSIS

432
Hygiene and antisepsis in
veterinary surgery

T Hygiene
he best way to prevent surgical principle covers different aspect of the
infection is to prevent contamination management of the patient and its
of or access to the surgical site by environment: disinfection, antisepsis, In a medical context, this includes all the to kennels, tables and clothes. Soap is
bacteria, either actively during surgery or asepsis and hygiene. techniques and practices aimed at the a great antiseptic, and can dramatically
later during hospitalisation. This simple prevention of the carriage and spread of reduce the degree of contamination and
bacteria within the hospital and between soiling: after cleaning, more than 99%
Disinfection patients, mainly by enforcing cleaning,
disinfection and antisepsis.
of bacteria are removed. Basic hygiene
measures that will decrease surgical
This includes the means and techniques and bacterial population. Increasing lev- sites contamination and possibly infection
of the destruction of the microflora els of disinfection are recognised, rang- Each veterinary practice should keep
include clean clothes (scrubs), easy
(bacteria, fungi, viruses, spores) from ing from non-critical (objects that can hygiene as a main focus of interest.
access to hand cleaning units in all
SYNOPSIS

SYNOPSIS
the surface of non-biologic material: be cleaned but not sterilized: a build- Cleaning is the first line of any of the
the rooms of the practice, hand clean-
instruments, implants and environment. ing, a room) and semi-critical (objects above practices. This means that an
ing between patients and use of gloves
The ultimate form of disinfection is ster- that directly in contact with the patient: antiseptic or disinfectant should be ap-
whenever handling or dressing open
ilization when all floras are destroyed. surgical table, kennels, which can be plied to an uncontaminated area that
wounds. Easy access to disposable gloves
In veterinary practice, this is only avail- disinfected frequently if not fully steri- has been thoroughly cleaned before ap-
and aprons (as well as hand rub dis-
able for small material (surgical kits, lized) to critical (surgical material, im- plication.
tributor or sinks and antiseptic soaps)
implants). The reality of disinfection is plants) where sterilization is required.
As antiseptics and sterilization will be al- is paramount to facilitate hygiene for
the control of the overall contaminants
tered or inhibited by residual organic tis- all hospital staff. Practices should have
sues and secretion and as all organic ma- written protocols regarding mainte-
Antisepsis terial harbours microorganisms, cleaning nance and cleaning of surgical theatres
This includes the means and techniques for the preparation of the surgical site is therefore the first line of hygiene. and kennels (frequency, type of disin-
for the destruction of the microflora and of the surgeon’s hands. Ideal anti- Strict cleaning protocols are paramount fectant to use, environmental testing for
(bacteria, fungi, viruses, spores) from septics have a broad-spectrum action, a throughout the building but also apply any residual flora), protecting of sterile
the surface of biologic material: skin or rapid activity, are not irritant or toxic and
mucosa, usually without full elimination do not impair the healing process. They

© Hervé Brissot
of the residing flora. Antisepsis is per- should not be inactivated by organic ma-
formed by using antiseptics following a terial and remain present and active for Figure 1 - In this operating theatre, both
dedicated protocol to ensure contam- a long time after application. The most surgeons are wearing sterile gloves and gowns.
inant removal without damaging the frequently use antiseptics in veterinary There is a limited team inside the theatre to
prevent airborne contamination due to
surface tissue and affecting its biology. medicine are denatured (75%) alcohol, displacement within the room. All staff should
In surgery, antiseptics are important povidone iodine and chlorhexidine. wear masks and headwear as well as dedicated
theatre shoes (washable orange and white clogs)
that should not be used outside the theatre.
Asepsis Sterile drapes cover the non-scrubbed body parts
of the patient and the instrument table.
A condition by which a tissue or surface or strategies used in surgery to prevent Note that the theatre is dedicated to surgery and
is free of micro-organisms. By extension, bacterial contamination. is not used for the storage of equipment/material.
aseptic techniques include all techniques

434 435
Hygiene and antisepsis in veterinary surgery

material (closed cabinets, sterility indi-


cators, dates of sterilization) and crea-
of sterile material, large surgical drapes
and the preparation of a large surgical
Surgical site preparation
tion of areas of restricted access (such site to limit the risk of contamination. The first step consists of clipping the Shaving should be avoided as this may
as surgical theatres) to prevent air tur- The surgeons should wear sterile surgical hair. Large areas should be clipped, cause trauma of the tissue and favour
bulence and contamination of the sur- gowns, gloves, a mask and headwear allowing a wide margin from the surgi- contamination by the inherent flora.
gical sites. cal site to prevent wound contamination.
to prevent oronasal bacteria and body
In the operating theatre, ensure the use hairs from contaminating the wound.
Skin cleaning and disinfection
Antibiotics should not be used as an alternative to proper The ideal antiseptic is non-toxic, has a dried with a soap to remove contami-
disinfection and asepsis. Good asepsis and hygiene will rapid action, is efficient against bacteria, nants. Next, antiseptics are applied and
reduce the need for antibiotics and markedly reduce the viruses, fungi and spores and remains left to act for a certain period of time.
SYNOPSIS

SYNOPSIS
risks of surgical infection. active after application. Three antisep- Chlorhexidine and iodophores can be
Cleaning should always be performed prior to disinfection. tics are commonly used in veterinary associated with soaps, improving the
practice: spirit (alcohol), iodophores and contact time. Contact time should be a
chlorhexidine. minimum of 5 minutes for alcohol (70%),
The area is first scrubbed, rinsed and chlorhexidine and iodophores.

a b
© Hervé Brissot

© Hervé Brissot
c d

Figure 2 - (a) Keep surgical theatres for surgical use only. After each procedure, the theatre is Figure 3 - Preparation of the surgical site before going into theatre includes wide hair removal
fully cleaned. Thorough disinfection is required on routine basis (e.g. weekly/monthly). All areas (clipping) and scrubbing in a centrifugal motion to ensure good decontamination/initial antisepsis
of the room should be treated, including the trolley wheels (b) and the ceiling lights (c). Swabbing before the final preparation in theatre. Note the use of disposable gloves and the removal of all
the prepared surfaces (d) will help monitor the efficacy of the disinfection protocol. hair (vacuuming) before antisepsis.

436 437
Hygiene and antisepsis in veterinary surgery

The surgeon
The surgeon’s hands and forearms ogenic resident flora. Over the last years,
hands are prepared with the same anti- the use of hydro-alcoholic rubs have
septics and soaps for the same duration been promoted and advocated for sim-
of time. Care should be taken to clean ple hand hygiene but also for “surgical
and remove all contaminants from under hands”. They act faster, are less aggres-
the nails. Frequent scrubbing may cause sive for the skin and are potentially more
skin dryness and irritation, which even- efficient in delaying the recolonisation of
tually may alter the normal non-path- hands inside the surgical gloves. n
SYNOPSIS

SYNOPSIS
© Hervé Brissot

Figures 4 - Surgical scrubbing may be replaced by a hydro-alcoholic rub. This is quicker and
does not require the use of water. The antisepsis lasts longer and is less irritant to the skin.

438 439
Key questions before
initiating any antibiotherapy

A
ntimicrobials are essential to are selected (not created) by antimi- The easiest way to prevent resistance is
cure bacterial infections but crobial use. It is impossible to eradi- to avoid systemic antimicrobials when
their use promotes selection of cate antimicrobial resistance unless they are not necessary, e.g. in cases of
resistant bacteria, thereby contributing we stop using antimicrobials. However, upper respiratory and enteric infections
to reduced antimicrobial efficacy over we can control and to some extent pre- that are self-limiting (i.e. infections that
time. Even though resistance is a nat- vent clinical challenges related to anti- resolve spontaneously with or without
ural phenomenon that exists regardless microbial resistance by using antimicro- specific treatment) or caused by virus-
of antimicrobial use, resistant bacteria bials in a rational way. es or parasites. Another way to reduce
overall antimicrobial use is by treating
the primary cause since bacterial in-
fections in companion animals are fre-
SYNOPSIS

SYNOPSIS
quently secondary to host-predisposing For otitis externa, superficial skin infections
factors and may represent and require and wound infections systemic antimicrobials
can be replaced by antiseptics
periodic antimicrobial therapy if the pri-
mary cause is not identified and treated
whenever possible.
In otitis externa, superficial skin infec- type of antimicrobial prescribed/used.
tions and wound infections systemic an- Other essential aspects of rational anti-
timicrobials can be replaced by antisep- microbial therapy include dose, admin-
tics, which have comparable therapeutic istration interval and treatment dura-
efficacy2, 4 and are not supposed to se- tion.
lect for resistance among commensal
microbiota outside the application site, Critical decisions on antimicrobial
such as in the gut where most bacteria choice are taken at two different steps
Antimicrobials are essential to cure bac­terial and opportunistic pathogens reside. in the diagnostic process: the first (em-
infections but their use promotes selection pirical) during the clinical examination
of resistant bacteria. We can limit this risk by Rational antimicrobial therapy is a of the animal and the second two to
using them in a rational way.
term that comprises any aspect of an- three days later, once laboratory results
timicrobial use that contributes to the (culture and sensitivity testing) have be-
optimisation of therapeutic efficacy come available.
During recent years, rational antimicrobial bacteria in dogs and cats5, 10. and/or the prevention of resistance in
therapy has gained considerable at- Carriage and infection with MDR bacte- the strain causing infection as well as In the first step, during clinical exami-
tention in companion animal medi- ria represent a major challenge for ef- in the patient’s commensal microbiota. nation, the veterinarian decides wheth-
cine due to the emergence of meti- fectively managing bacterial infections Antimicrobial choice is a cornerstone er bacterial culture is indicated, selects
cillin-resistant staphylococci (MRSA as well as for preventing nosocomial in- of rational antimicrobial therapy as both the most appropriate specimen for sub-
and MRSP), Escherichia coli producing fections and zoonotic risks to veterinary therapeutic efficacy and prevention of mission to the laboratory, and evaluates
extended-spectrum ß-lactamase (ESBL) staff and pet owners. resistance are strongly influenced by the the need for empirical antimicrobial
and other multidrug-resistant (MDR)

440 441
Key questions before initiating any antibiotherapy

therapy. Subsequently, if samples have


been submitted to the laboratory, they
to initiate therapy or correct empirical
therapy if necessary (Figure 1).
First visit
interpret antimicrobial susceptibility data The critical decisions to be taken during the first visit can be summarized in three
questions (Q1 to Q3):

1- Is empirical antimicrobial therapy needed?


Empirical therapy is recommended if: • collection of a suitable clinical sample
• bacterial infection is suspected on the requires invasive procedures that may
basis of well-grounded clinical data, complicate infection or patient stability,
Empirical • infection is life-threatening or causing • interpretation of the culture result
Patient is hampered by contamination with
choice pain or discomfort in the patient,
SYNOPSIS

SYNOPSIS
Sample selection Diagnosis commensal bacteria, or
• delay in treatment could adversely
& collection & therapy • infection requires topical antimicrobial
affect the clinical outcome,
therapy.

2 - If yes, which drug should be used/prescribed?


The drug(s) recommended as first choice therapy with broad-spectrum drugs
for empirical therapy of specific infec- such as 3rd generation cephalosporins
Microbiology Choice
tions are reported in the Disease Fact or fluoroquinolones should be avoided
based
diagnostic on C&AST Sheets chapters. A qualified choice re- unless the infection is life-threatening
process quires basic knowledge of the pharma- or is an infection for which one of these
cology of antimicrobial agents, of the drugs is recommended as first choice
causative agents of bacterial infections (e.g. fluoroquinolones are recommend-
in companion animals and of the local ed as first choice in the management of
patterns of antimicrobial resistance. In acute or chronic prostatitis due to their
particular, the drug should be: ability to pass the blood-prostate barri-
• able to penetrate and be active at the er).
Sample Data infection site,
transportation interpretation In other situations, the narrower spec-
• active on the most likely bacterial trum drugs should be chosen, since
Laboratory analysis species suspected to be responsible broad-spectrum cephalosporins and fluo-
for infection, roquinolones have a considerable impact
Figure 1 - During the microbiology diagnostic process, critical decisions on antimicrobial choice • be non-toxic to the patient, on the commensal flora and promote
are taken by the clinician during the first visit (empirical choice) and when interpreting the results selection of multidrug-resistant bac-
of antimicrobial susceptibility testing (choice based on C&AST). • easy to administrate and
teria (see recommendation R.20). For
• as narrow spectrum as possible.
certain types of infections (e.g. otitis,
With regard to the last point, empirical skin infections and UTIs), antimicrobial

442 443
Key questions before initiating any antibiotherapy

choice should be guided by cytology (see


recommendation R.2). Local patterns of
reports, scientific articles or even better
from retrospective analysis of the sus-
For an optimal prescription
resistance may be gathered from national ceptibility data at the clinic level. Another set of critical decisions have to be taken in order to perform an optimal
prescription (Q4 to Q7):

3 - Regardless of whether empirical therapy is initiated or not, should 4 - What is the most appropriate dose?
a clinical specimen be submitted to the microbiology laboratory? As a matter of principle the dose should doses, the highest dose is recommended
Even if empirical therapy is initiated, • there is any reason to suspect infection follow the label instructions provided by for concentration-dependent drugs such
culture and antimicrobial susceptibility with MDR bacteria on the basis of the antimicrobial drug manufacturer. If as the fluoroquinolones in order to en-
testing (AST) are recommended if: anamnesis and clinical records. the label instructions indicate that the hance therapeutic efficacy and prevent
• there is suspicion of a complicated drug can be administered at different selection of resistant mutants3.
Culture and AST are indispensable if:
SYNOPSIS

SYNOPSIS
infection (i.e. an infection associated • the patient is immunocompromised, 5 - What is the most appropriate administration interval?
with structural or functional abnor-
• the infection is life threatening (see The interval at which a drug is adminis- influences prevention of resistance to
malities or the presence of underlying
recommendation R.3). tered is particularly important for time- concentration-dependent drugs such as
disease, which increases the risks of
dependent antimicrobial drugs such fluoroquinolones. Delayed administra-
failing therapy), Information on how samples should be
as all ß-lactams since therapeutic tion may lower the drug concentration
• the patient has not responded to therapy collected is provided in recommendation
efficacy is affected if these drugs are below the mutant prevention concentra-
or has a history of relapse or re-infection, R.4.
not prescribed according to the rec- tion (MPC), thereby increasing the risk of
ommended interval (e.g. q12 or q8 selecting resistant mutants during ther-
hours). The administration interval also apy3.
6 - What is the most appropriate treatment duration?
This question is difficult to answer due by scientific evidence (see recommen-
to knowledge gaps. For some infections dation R.20). The latest trend in human
the recommended courses of antimicro- medicine is that unnecessary treatment
bial therapy in veterinary medicine are should be avoided after clinical resolu-
significantly longer than for human med- tion of symptoms.
icine and this difference is not justified

7 - Which antibiotic to choose?


A clear distinction should be made When choosing an antimicrobial based
between empirical choice and choice on susceptibility data, the choice should
Broad-spectrum drugs such as based on susceptibility testing results. fall on the drug that has the least possi-
3rd generation cephalosporins or
fluoroquinolones have a considerable
This important distinction is largely ble impact on selection of multidrug-re-
impact on the commensal flora overlooked in most veterinary guidelines sistant bacteria, provided that the drug
and promote selection of for antimicrobial use, which usually only is clinically effective and non-toxic.
multidrug-resistant bacteria. provide recommendations on antimicro-
bial choice for empirical therapy.

444 445
Key questions before initiating any antibiotherapy

Off-label use of products registered for the tested strain is resistant to all antimi- • Use of CIAs in small animals is only disease specialist. Specific require-
human use should only be considered if crobial agents licensed for veterinary use. justified in rare cases of life-threat- ments for the use of CIAs have been
ening multidrug-resistant infections defined in the Danish guidelines6 or,
that cannot be managed otherwise and sometimes, in national regulations.
only after consultation with an infectious
SYNOPSIS

SYNOPSIS
Risk for selection of MDR bacteria of high concern in veterinary medicine

Critically important antimicrobials (CIAs) in human medicine


CARBAPENEMS
LINEZOLID
VANCOMYCIN

AMIKACIN
METRONIDAZOLE
FLUOROQUINOLONES
EXTENDED-SPECTRUM CEPHALOSPORINS
GENTAMICIN
AMOXICILLIN CLAVULANATE
FIRST GENERATION CEPHALOSPORINS
When choosing an antimicrobial based on susceptibility data, the choice should fall on the drug RIFAMPICIN
that has the least possible impact on selection of multidrug-resistant bacteria, provided that the
drug is clinically effective and non-toxic. NITROFURANTOIN
AMINOPENICILLINS
LINCOSAMIDES
TRIMETHOPRIM-SULFONAMIDES
The priority system proposed by the human medicine (e.g. chloramphenicol). TETRACYCLINES
Danish guidelines for antimicrobial • The higher to the top, drugs have an CHLORAMPHENICOL
use in animals ranks the antimicrobial increasing importance in human MACROLIDES
classes into five categories (Figure 2): medicine and higher potential for
PENICILLINS
STREPTOMYCIN
• The lowest category, at the bottom selection of clinically relevant
of the pyramid includes drugs with resistance phenotypes. The fifth and
Figure 2 - Danish classification of systemic antimicrobials based on their critical importance in
narrow spectrum and limited risk for highest category contains critically human medicine and the risk of selecting multidrug-resistant (MDR) bacteria of high concern in
selection of multidrug-resistant bacteria important antimicrobials (CIAs) in veterinary medicine. Drugs with very limited or no therapeutic alternatives in human medicine
found in small animals (e.g. penicillins, human medicine that are not licensed and high risk of selecting MDR bacteria are located on the top layer of the pyramid. (From the
macrolides and streptomycin) or drugs for veterinary use, namely carbape- Danish antimicrobial use guidelines for companion animals 6).
that are not used for systemic therapy in nems, vancomycin and linezolid.

446 447
Key questions before initiating any antibiotherapy

C&AST interpretation 10 - Which antimicrobial should be chosen when laboratory report


Interpretation of C&AST reports is not as simple as it may appear on the surface.
includes susceptibility profiles of multiple strains?
The critical decisions to be taken when interpreting C&AST reports can be summa- Some infections, mainly wound infec- specimens that may complicate antimi-
rized with five questions (Q8 to Q12): tions, otitis externa and to a lesser crobial choice when interpreting C&AST
extent UTIs, often result in culture of results.
multiple bacteria. In these situations, A good microbiology laboratory should
8 - Why are some of the antimicrobials used in clinical practice not
cytology can be helpful in determining not indiscriminately report everything
included in the panel of antimicrobials tested by the microbiology the relative abundance of cocci and that grows. It should indicate results
laboratory? rods. The clinical relevance of each that may be clinically insignificant
Clinical breakpoints (i.e. the threshold microbiology laboratories as surrogate organism reported by the laboratory due to likely contamination or even
SYNOPSIS

SYNOPSIS
values used by diagnostic laboratories drugs for susceptibility testing (see should be considered based on its path- exclude those from the report. Reporting
to categorize strains as resistant, recommendation R.8). ogenicity. For example, Corynebacteri- accurate but insignificant results can
intermediate or susceptible) are lacking Clinical breakpoints are also lacking for um auriscanis is unlikely to be a primary be as counterproductive as reporting
for some antimicrobials that are used some drugs that are used for topical pathogen in otitis externa as it is never inaccurate results and can have serious
in clinical practice (e.g. cefalexin and ce- treatment in veterinary medicine (e.g. isolated alone1. Anecdotal evidence sug- consequences to patient care and the
fovecin). fusidic acid). gests that otitis externa associated with development of resistance.
this organism resolves if the primary
In the absence of clinical breakpoints, For others (e.g. enrofloxacin and gen-
pathogen is targeted by antimicrobial
surrogate drugs belonging to the same tamicin) there are clinical breakpoints
therapy.
antimicrobial class and displaying for systemic therapy but their use for
similar pharmacodynamics and phar- predicting efficacy of topical therapy is Targeting the primary pathogen is the
macokinetic properties may be used by questionable (see recommendation R.3). most reasonable approach since tar-
geting all the strains cultured may be
9 - Why are some antimicrobials tested by the microbiology laboratory difficult and lead to unnecessary use of
broad-spectrum antimicrobials. Con-
not available for use in clinical practice?
sidering the most common infections
One of the most common problems For example, oxacillin and cefoxitin are in companion animals, Staphylococ-
encountered in the interpretation of used for detection of MRSA and MRSP cus pseudintermedius should always
susceptibility reports is the presence of (meticillin resistant Staphylococcus). be regarded as the primary pathogen
antimicrobial agents that are not used in Information on how to interpret sus- in pyoderma, Escherichia coli in UTIs
clinical practice. Some agents are used ceptibility data of drugs that are not and Pseudomonas aeruginosa in otitis
as indicators for testing susceptibility used in veterinary clinical practice but externa. Coagulase-negative staphy-
to clinically relevant drugs belonging to are commonly included in the panels of lococci (skin contamination), Bacillus
the same class or subclass. Others are antimicrobials tested by microbiology When multiple bacteria are cultured, cytology
spp. (soil contamination) and enterococci can be helpful in determining the relative
used to detect specific resistance phe- laboratories are provided in recommen- (faecal contamination) are among the abundance of cocci and rods.
notypes of clinical relevance. dation R.8. most common contaminants of clinical

448 449
Key questions before initiating any antibiotherapy

11 - Should therapy be changed if the strain is reported as resistant to


the antimicrobial that was prescribed empirically?
In theory, the initial therapy should be can be eradicated even if the causative
interrupted and a new drug should be agent is reported as resistant (see
chosen from among those to which the Recommendation R.10). Thus, the pa-
strain is susceptible. However, this is not tient’s condition and treatment outcome
necessarily a wise decision since various should always be checked before chang-
studies have shown that the therapeutic ing antimicrobial therapy based on
outcome is not always predicted by in C&AST results.
vitro susceptibility testing and infection
SYNOPSIS

SYNOPSIS
12 - Why must antibiotics such as carbapenems and vancomycin not be
used in veterinary practice?
These antibiotics are “last resort” drugs resistance pathogens such as car-
for the therapy of life-threatening con- bapenemase-producing bacteria that
ditions in humans; currently there are have also been isolated in companion
no veterinary preparations available animals7,8 . Carriage of vancomycin-
with these substances. Carbapenems resistant enterococci has been report-
are indicated for treating infections in ed in healthy companion animals11.
humans caused by multidrug resistant Therefore, it is essential to prevent the
Enterobacteriaceae, while vancomycin further spread of these genetic deter-
has been widely used to treat MRSA minants to other bacteria that could be
infections in humans11. Resistance to potentially harmful to both public and
these antibiotics has been reported in animal health. n
recent years, with the emergence of

Carbapenems and vancomycin


must not be used in veterinary practice
because they are so-called last resort drugs
for the therapy of life-threatening
conditions in humans.

450 451
PharmaCological basis of
antibiotic theraPY

T
he likelihood of antibacterial ef- with the least toxicity, but should also
ficacy depends on the poten- minimize the risk of bacterial resistance Dosing regimen of
cy of a drug against a pathogen emerging during therapy. Antimicrobial the antimicrobial drug
(usually expressed as the MIC), pa- agents should not be misused (Table 1).
tient exposure to a drug (the concen-
tration of antimicrobial agent availa-
ble for effect over time) and the host Potency of the
defences. Antibacterial drugs are Exposure to the drug
antimicrobial drug
needed only if the host defences are in vivo (PK)
in vitro (MIC)
inadequate. The exposure to the antimi-
crobial agent is dependent on the drug
SYNOPSIS

SYNOPSIS
pharmacokinetics and the dosing regimen.
The beneficial effects on the host will PK/PD Host
depend on the killing or growth inhibition profile defences
of the bacteria. The dosing regimen should
be optimized so that the primary aims
(clinical outcome, resistance suppression) The treatment target should be the achieve-
of the antimicrobial therapy are reached. ment of a good clinical outcome with the In vivo
least toxicity, but should also minimize the
The treatment target should be the achieve- risk of bacterial resistance emerging during
ment of a good clinical outcome (clini- therapy.
cal/bacteriologic cure and no relapse)

Table 1 - Common misuses of antibioticsadapted from 4.

Common misuses of antimicrobial agents


Antimicrobial efficacy
Prolonged empirical antimicrobial treatment without clear evidence of infection (e.g.
inflammatory syndromes can be present with signs that mimic infectious diseases). of the drug
(antimicrobial cure)
Treatment of a positive clinical culture in the absence of disease (e.g. asymptomatic
urinary tract infection).
Failure to use narrow spectrum antimicrobial therapy when a causative pathogen is
identified (e.g. prolonged used of broad-spectrum antimicrobials).
Clinical outcome
Prolonged prophylactic therapy (e.g. pre and postsurgical prophylaxis).
(clinical cure)
Excessive use of certain antimicrobial agents (e.g. excessive prescribing of a single
class of antibiotic). Figure 1 - Determinants of clinical outcome. The PK/PD profile of the antimicrobial drug within
the host can be used to predict the likelihood of antimicrobial efficacy adapted from 9.

452 453
Pharmacological basis of antibiotic theraPY

Main principles for antibiotic therapy Bactericidal agents are not more efficient than bacteriostatic agents
A very common hypothesis in antimi- suitable clinical data exist to address
Need for an accurate infectious disease diagnosis crobial therapy is that agents with in the potential superiority of bactericidal
Site of infection, characteristics of the of prolonged antimicrobial therapy. vitro bactericidal activity should be pre- versus bacteriostatic activity. In vitro re-
host (e.g. immunocompromised, geriat- Similarly, if an empirical antimicro- ferred to agents with in vitro bacterio- sults should be combined with pharma-
ric, comorbidities), and, whenever pos- bial therapy based on clinical pres- static activity (see Table 2 page 460). The cokinetic and pharmacodynamic data
sible, cytological and microbiological entation has failed, further laboratory rational is that bacteriostatic drugs, to provide more meaningful prediction
diagnosis are requirements for appro- investigations should be performed to contrary to bactericidal drugs, require of in vivo efficacy. Potentially adverse
priate antimicrobial therapy. Although determine the causal pathogen. Any the aid of host defences to clear the clinical consequences may also result
the “most likely” microbiological aetiol- possible non-infectious conditions infecting pathogen. Most antibacterials from the rapid lytic action of bactericidal
ogy can be frequently inferred from the should be excluded. The number of however, are potentially both bacte- agents10.
SYNOPSIS

SYNOPSIS
clinical presentation, identification of bacteria should be also estimated by the ricidal and bacteriostatic. Little to no
the specific pathogen is critical in laboratory to distinguish colonization
life-threatening infections and/or in case from infection.
Inadequate penetration of the infection site can induce failure of anti-
Need for antimicrobial sensitivity testing bacterial therapy
After identification of the pathogen by Although AST results are quite helpful To be effective, the antimicrobial agent extracellular space.
culture, the next step for the clinical mi­ for the selection of the antimicrobial must be distributed to the site of infection, However in the central nervous system,
crobiology laboratory is the antibiotic agent, other factors should be also which most often is extravascular. The eye, prostate, bronchial secretions and
susceptibility testing (AST) of significant taken into account, such as the nature drug penetration depends on tissue- the mammary gland, drug distribution
bacterial iso­lates. AST measures the and the site of infection and the tissue related factors, such as local blood flow, is limited because of membrane bar-
ability of the pathogen to grow in the distribution of the antibiotic. vascular surface area, type of vascu- riers. Lipophilic antibacterial drugs
presence of an antimicrobial agent in larisation (fenestrated capillaries, tight (e.g. fluoroquinolones, metronidazole,
vitro, and therefore predict the clinical junctions…) and drug-related factors chloramphenicol, tetracyclines, sulfon-
success or failure of the antibiotic being (lipid solubility, pKa, molecular size, amides, trimethoprim) can cross some
tested. Results are reported as mini- and plasma protein binding). In most of these barriers very readily, in con-
mum inhibitory concentration (MIC) (i.e. tissues, free antibacterial concentrations trast to hydrophilic drugs (penicillins,
the lowest concentration of an antibiotic in serum/plasma are directly related cephalosporins, aminoglycosides).
that inhibits visible growth of a microor- or equal to the concentration in the
ganism), and are interpreted by the lab-
oratory as “susceptible,” “resistant,”
or “intermediate”.
Rational antibiotic combination therapy may be more effective to
The MIC is the best way of measuring Culture and AST results are helpful for the combat multidrug resistance
an antibacterial effect in vitro and this selection of the antimicrobial agent, but the Antimicrobial monotherapy is generally completely eradicate target microor-
knowledge can also be used to tailor nature, the site of infection and the tissue
distribution of the antibiotic should also be preferred to combination therapy. However, ganisms without leaving any mutants
treatment to an individual patient. taken into account. in case of multidrug resistance the should be selected. In such clinical
appropriate empirical therapy that can settings there is a higher possibility

454 455
Pharmacological basis of antibiotic theraPY

of adequate antibacterial coverage by However, combination therapies poten- de-escalation). Delay in the start of suit- should be encouraged as it is one of the
combining two antibacterial agents tially have some disadvantages: able antibiotic therapy may lead to treat- simplest and most effective ways to re-
rather than a single agent. Combined ment failure and increased drug resist- duce exposure of commensal bacteria
• encouragement of “shotgun therapy”,
antibacterial agents with their broad ance, although the impact on patient to antimicrobial agents. Moreover they
spectra of activity and multimodal action • failure to provide an optimum dose of outcome remains poorly documented in improve the owner’s compliance, reduce
may prevent emergence of drug resistance. individual drugs, veterinary medicine3, 4, 8. the cost of the therapy and limit the risk
Synergistic action resulting from com- • increased drug resistance by providing of adverse effects. A very simple prin-
bination therapy leads to broader Although recommendations regarding ciple is that the longer the duration of
empirically two agents if the organism is
spectrum than the sum of activity of the susceptible to a single agent, the duration of treatment exist in small therapy the higher the risk of resistance
two individual agents. Antibiotic combi- animals, there is no evidence-based emerging. In practice, the treatment has
nation therapies are also the mainstay • cost of the therapy. guidance on optimal duration of anti- to be carefully individualized and should
SYNOPSIS

SYNOPSIS
of treatment of polymicrobial infections microbial therapy. Short (at least not be discontinued once there is evidence
Although data are missing in veterinary
especially of mixed infection with each abusively long) durations of treatment of clinical and microbiological cure13.
medicine, judicious and rational use
pathogen requiring a different drug. In
of antibiotic combination therapy is
patients where the nature of infection
recommended by various society guide-
is not clear, empirical antibiotic combi-
lines in human medicine8.
nations can be very useful to initiate the
therapy1,8,9.
Host factors should be considered before selecting the antimicrobial
Timing of initiation and duration of antimicrobial therapy should be agent
rationally guided by the clinical condition and laboratory results In patients with renal (or hepatic) dys-
function, drug pharmacokinetics (PK)
The timing of initial therapy should be especially the elimination of drugs may
guided by the clinical condition. In sta- be altered and lead to overexposure
ble, non-urgent clinical settings, anti- for drugs that are essentially cleared
microbial therapy should as much as by the kidney (or the liver). Although
possible be deliberately delayed until in such situations the dosage regimen
microbiology results are available. This can be adjusted, it is preferable to se-
is not always easy to explain to an owner, lect antimicrobial drugs cleared by the
who might expect immediate treatment. extrarenal (or extrahepatic) route. For
In critically ill patients, empirical an- drugs cleared by both hepatic and renal
timicrobial therapy should be initiated pathways, accumulation due to renal
immediately after or concurrently with impairment may be compensated by
the taking of samples for laboratory increased hepatic elimination6. Age-as-
diagnosis. Once the pathogen and sociated physiological differences could
antimicrobial susceptibility are known, Short treatments reduce the risk of emer- also affect antimicrobial drug PK (e.g.
Surgical incision and drainage, and not
every attempt should be made to narrow gence of resistance. antimicrobials, are the key treatment for
excretion of antibacterial drugs in urine abscesses.
the antibiotic spectrum (downscaling or depends on the glomerular filtration

456 457
Pharmacological basis of antibiotic theraPY

rate, which is 87% higher in puppies than Surgical incision and drainage, not an- In contrast, drugs with a time-depend- • For ß-lactams, time>MIC values at
in mature dogs5). Antimicrobial drugs timicrobials, are for example the key ent effect have relatively slow bacteri- least equal to 40-50% of the dosage in-
should be also prescribed with caution treatment for abscesses. cidal action. It is therefore important terval have been proposed.
during pregnancy and lactation. Genetic that plasma concentrations exceed the • For aminoglycosides, Cmax/MIC of 8-10
diversity observed in dogs and cats may The clinical history of antimicrobial ther- MIC as long as possible during the dos- is the most closely correlated with effi-
also cause variability in antimicrobial apy should be also documented, as pri- ing interval, either via continuous infu- cacy. This can be accomplished by a sin-
agent PK, even if insufficient data are or administration of antimicrobials may sion or by frequent dosing. gle dose once daily.
currently available for breed-specific induce development of strains of resist- • For fluoroquinolones, AUC/MIC ratio
recommendations7. ant bacteria through selective pressure. Frequently used PK/PD indices for the >100-125 has proved to be the most pre-
Avoiding recently used antimicrobials assessment of antimicrobial efficacy are dictive of efficacy.
Adjunctive non-antimicrobial treatment is therefore recommended when chos- the time above MIC, peak plasma con- • For bacteriostatic drugs (e.g. mac-
SYNOPSIS

SYNOPSIS
(debriding necrotic tissues, removing for- ing the appropriate drug2. Patients with centration to MIC ratio, and area under rolides, tetracycline, clindamycin and
eign bodies and other sources, removing immune suppression (e.g. patients with the curve (AUC) to MIC ratio (Figure 2). chloramphenicol), time>MIC is used to
predisposing causes, nursing…) should cancer or neutropenia) should be also predict efficacy11. n
not be neglected in the infected patient identified as they may respond poorly to
and may be equally or even more im- the antimicrobial therapy.
portant than antimicrobial therapy12.
Cmax
Understanding how dosing affects the antimicrobial activities of diffe-
rent agents is required for appropriate antimicrobial therapy

Plasma concentration
An understanding of the relationships Antimicrobial bactericidal drugs can
between pharmacokinetic (PK) and be distinguished by their action mech-
pharmacodynamic (PD) parameters anism: concentration dependent (e.g. Cmax/MIC
allows a better correlation of in vitro aminoglycosides and fluoroquinolones)
potency and in vivo efficacy. MIC is the or time-dependent (e.g. ß-lactams).
most frequently used PD parameter.
Drugs with concentration-dependent
AUC
However, it is not representative of the
in vivo process involved in the antibac- effect have an enhanced bactericidal MIC
terial effect over time. Integration of PK activity at high plasma concentration.
and PD data can therefore predict the With these agents, the peak plasma Time > MIC
antibacterial efficacy against a given concentration (and not the frequency of
pathogen. PK/PD relationships are also administration) is more closely associ-
ated with efficacy. Time
essential for determining the dosage
regimen. Figure 2 - The most frequently used PK/PD indices for antibiotics.
The Cmax/MIC and the AUC/MIC are indices of the efficacy of dose-dependent antibiotics.
The time above MIC (T> MIC) is used for time-dependent antibiotics.

458 459
Pharmacological basis of antibiotic theraPY

Table 2 - Definition of bacteriostatic/bactericidal drugs, and current limitations of this Table 2 (continued).
categorization10.
Bactericidal drug Bacteriostatic drug Comments Bactericidal drug Bacteriostatic drug Comments
General definition Examples of so-called bactericidal or bacteriostatic drugs
The agent kills The agent prevents the Bactericidal agents usually fail to Aminoglycosides, Tetracyclines, At high concentrations, bacterio-
bacteria growth of bacteria (i.e. kill all bacteria, especially if the fluoroquinolones, macrolides static agents may be bactericidal
it keeps them in the inoculum is large, while most so- ß-lactams against some susceptible or-
stationary phase of called bacteriostatic agents kill ganisms. At low concentrations,
growth). some bacteria. In vitro conditions bactericidal drugs may exhibit
of testing (growth condition, test bacteriostatic activity. A high in
SYNOPSIS

SYNOPSIS
duration…) may influence whether vivo bacterial load may affect the
an antimicrobial agent is consid- activity of bactericidal drugs.
ered bactericidal or bacteriostatic.
Microbiological definition
The generally accept- Bacteriostatic activity There is no evidence that a > or
ed definition of bac- has been defined as <99.9% decrease might not be
tericidal is a 99.9% a ratio of MBC to MIC equally useful in predicting clin-
reduction in viable of >4. ical outcome. The extension of
bacterial density in an the incubation time from 18-24 h
18-24-h period. The to 36 h or even 48 h could also
minimum bactericidal change the classification of many
concentration (MBC) antibacterial agents from bacte-
is the lowest con- riostatic to bactericidal, or vice
centration of an an- versa. MBC is the result of an
tibacterial agent that in vitro test in which a static
either totally prevents concentration of an antibacteri-
growth or induces a al agent is being tested against
99.9% decrease in the an initially fixed concentration of
initial inoculum (i.e. pathogens in an aqueous medi-
a 3log10 reduction in um. This differs from the in vivo
colony-forming units situation, in which antibacterial
[cfu]/mL). and bacterial concentration in
various body fluids and tissues Cytological and
may change considerably over microbiological
time. diagnoses are
requirements for
appropriate
antimicrobial therapy.

460 461
Current situation of antibiotic resistance
in dogs and cats, emerging resistance patterns

V Resistance in companion animal bacterial pa-


eterinary care of companion animals
has evolved in recent years8,18.
In many countries, companion thogens
animals are now perceived as family
members3,8. This has resulted in an Data on susceptibility of canine and feline bacterial pathogens is scarce and fragmentary
increased use of veterinary services3, and due to the lack of surveillance programs for antimicrobial resistance in these species.
consequently of antimicrobial substance
in these species17,18. Pet animals can act Current resistance scenario in UTI bacterial pathogens
as both source and reservoirs of resist- Recently, a multicenter study of urinary resistance compared to Northern
ant bacteria and determinants. This pos- tract infection susceptibility was conduct- European countries. This may be asso-
es a risk for pet owners due to the close Pet animals have close social interactions ed in companion animals in 14 countries ciated with the various national antibi-

SYNOPSIS
SYNOPSIS

social interactions and sharing of the with pet owners and can act as both source in Europe24. For all bacterial species, otic prescription habits in the countries
same environment in the household18. and reservoirs of resistant bacteria.
Southern European countries generally concerned (Figure 1 and Table 1).
It also poses an occupational risk to showed higher levels of antimicrobial
veterinary professionals, as they are
at higher risk of colonisation with re- to what is observed in humans8, 18, 23, 43. All
sistant and multidrug resistant patho- groups of antimicrobials used in veteri- 100%
gens than individuals in the community nary practice are also routinely used in 90 %
and increases the risk of nosocomial human medicine. Of particular interest
80%
infections in the workplace23,27. Pets is the growing use of veterinary approved
70%
can become colonised or infected with cephalosporins and fluoroquinolones,
60%
resistant strains in many ways: contact to treat common infectious diseases in
50%
with other animals, humans, contami- small animals, that are deemed as crit-
40%
nated environment (including that of the ically important antimicrobials (CIAs)
for the treatment of life-threatening 30%
veterinary practice), food and treats of
infections in humans9,44. Furthermore, 20%
animal origin. Contaminated dog food
and pig ear treats have been associat- besides the CIAs that are approved for 10%

ed with multidrug-resistant Salmonella veterinary use there are those approved 0%

m
ria

ce

ce

ly

ds

al

ia

in

en

nd
for human use only (e.g. carbapenems,

an
ar
spp. in dogs38. The increased popularity

Ita

rb

do
a
g
iu

an

ee

an

ed

la
st

Sp
tu
nm

rm
lg

Se

ng
er
Au

Gr
Fr

rl

Sw
r
fosfomycin, vancomycin). Although cur-

Be

Po
Ge

he

itz
of raw meat diets may also pose a risk

De

Ki
Sw
et

d
ite
rently a controversial issue, a veterinary

N
to public health22.

Un
surgeon may exceptionally prescribe the
The epidemiology of antimicrobial re- latter (CIAs for human use only), in par- Amoxi + Clavulanate TMPS
Gentamicin Fluoroquinolone
sistance in companion animals is still not ticular to avoid unacceptable suffering,
Cefovecin % MDR
completely understood. Antimicrobial to treat the animal in accordance with
use is a known risk factor for the emer- the ‘‘Cascade’’ (Arts. 10 & 11 of Directive Figure 1 - Percentage of resistance in urinary Escherichia coli by antimicrobial and country in
gence of resistance and colonisation 2001/82/EC of the European Parliament 2012-201324.
with resistant bacteria in pets, similar and of the Council).

462 463
Current situation of antibiotic resistance in dogs and cats,
emerging resistance patterns

Amoxicillin-clavulanate resistance
Denmark (2.88%) and Belgium (4.29 %) conducted in dogs in Portugal prior to Table 1 - Percentage of resistance in urinary Escherichia coli by antimicrobial and country in
2012-201324.
had the lowest frequencies of amoxi- 200214,15 and in dogs and cats from Ger-
cillin-clavulanate resistance in E. coli. many in 2004-200616 and Switzerland in Amoxi + Fluoro-
Cefovecin Gentamicin TMPS % MDR Zero R %
In Portugal, E. coli had a significantly 2000-200121 described lower frequen- clavulanate quinolone
higher amoxicillin-clavulanate resist- cies of E. coli resistance. 14,1 % 5,6 % 12,0 % 5,6 % 14,1 % 8,4 % 78,9 %
Austria
ance frequency (48.15%). Earlier studies (n=142) (n=142) (n=142) (n=142) (n=142) (n=142) (n=142)
4,3 % 6,6 % 1,7 % 10,4 % 1,4 % 85,1 %
Belgium (n=0)
Third-generation cephalosporins (n=840) (n=769) (n=840) (n=839) (n=769) (n=769)
E. coli resistance to third generation Spain (21.15%). Being of critical impor- 2,9 % 3,9 % 2,9 % 1,9 % 8,2 % 2,4 % 88,9 %
Denmark
(n=206) (n=208) (n=208) (n=208) (n=208) (n=208) (n=208)
SYNOPSIS

SYNOPSIS
cephalosporins (3GC) had also the highest tance to humans, prudent use of 3GC is
frequencies in southern countries: of upmost importance. 12,8 % 10,8 % 12,8 % 3,4 % 16,3 % 11,0 % 77,2 %
France
(n=954) (n=933) (n=948) (n=951) (n=959) (n=909) (n=909)
Portugal (31.25%), Italy (24.64%) and
11,8 % 11,8 % 16,3% 1,2 % 17,7 % 8,6 % 67,8 %
Germany
(n=153) (n=152) (n=153) (n=153) (n=153) (n=152) (n=152)
Trimethoprim-sulfamethoxazol 25,8 % 77,8 % 30,0 % 34,6 %
E. coli resistance to trimethoprim-sul- southern countries, and even over 30% Greece (n=0) (n=0) (n=0)
(n=31) (n=9) (n=30) (n=26)
famethoxazol (TMPS) was over 25% in in Portugal, Greece and Serbia. 26,1 % 24,6 % 31,9 % 14,5 % 29,0 % 29,0 % 63,8 %
Italy
(n=69) (n=69) (n=69) (n=69) (n=69) (n=69) (n=69)
Fluoroquinolones Netherlands
10,8 % 3,8 % 4,9 % 3,7 % 10,2 % 2,2 % 81,3 %
Several authors have reported lower quinolones are considered a good first (n=1461) (n=1380) (n=1457) (n=81) (n=1459) (n=1380) (n=1380)
fluoroquinolones resistance frequen- choice for pyelonephritis treatment and 48,1 % 31,3 % 29,0 % 10,0 % 32,3 % 24,0 % 32,0 %
Portugal
cies16,29,37,45 than the ones found in this should otherwise be used as a second (n=27) (n=31) (n=31) (n=30) (n=31) (n=25) (n=25)
study, especially regarding southern line antimicrobial for the therapy of low- 66,7 % 50,0 % 100 % 100 % 33,3 % 50,0 % 50,0 %
Serbia
countries. In emergency cases, fluoro- er UTIs. (n=3) (n=2) (n=3) (n=3) (n=3) (n=2) (n=2)
31,7 % 21,2 % 29,6 % 26,6 % 26,7 % 29,7 % 43,2 %
Spain
(n=60) (n=52) (n=61) (n=46) (n=60) (n=37) (n=37)
Gentamicin
7,0 % 0% 1,1 % 0,2 % 5,0 % 0,2 % 90,2 %
Resistance to gentamicin was low in E. distribution seemed to follow the same Sweden
(n=2091) (n=2082) (n=2091) (n=2091) (n=2091) (n=2082) (n=2082)
coli, Proteus spp. and Staphylococcus pattern, with increased resistance in 10,5 % 7,5 % 13,6 % 6,8 % 13,7 % 10,0 % 83,1 %
spp. over Europe. Nevertheless, the southern over northern countries. Switzerland
(n=133) (n=132) (n=132) (n=132) (n=131) (n=130) (n=130)
United 21,7 % 19,0 % 11,9 % 6,5 % 21,1 % 14,6 % 69,7 %
Multidrug resistance Kingdom (n=143) (n=142) (n=143) (n=92) (n=142) (n=89) (n=89)
Multidrug resistance (resistance to three several antimicrobials including fluo- n: Total number of Escherichia coli tested for the considered antibiotic category.
or more categories of antimicrobials) roquinolones decreased significantly in MDR : multidrug-resistant isolates are defined as those resistant to three or more categories of antimicrobials in this table
was also higher in E. coli in Southern E. coli isolates in Belgium, Denmark, Zero R: full-susceptibility is defined as an isolate being susceptible for all the above-mentioned classes of antimicrobials.
European countries. During the study France and the Netherlands24. MDR and Zero R percentages do not include resistance to cefovecin for Belgium and gentamicin for the Netherlands.
period, the frequency of resistance to

464 465
Current situation of antibiotic resistance in dogs and cats,
emerging resistance patterns

Current scenario in Staphylococci resistance Multidrug-resistant bacteria in companion ani-


Three studies evaluated antimicrobial neomycin, tobramycin, kanamycin,
resistance in Staphylococcus pseudin- streptomycin, erythromycin was seen in mals
termedius over time2,6,26. all staphylococci analysed6 (see Figure Recently, the European Medicine Agency poses a particular risk for both animal
The studies detected increasing resist- 2 for resistance mechanisms). The in- (EMA) has voiced its growing concern over and public health phenotype; exposure
ance trends for ampicillin/amoxicillin/ crease over time of meticillin-resistant antimicrobial resistance by publishing a to antimicrobials has been associated
penicillin, cefovecin, cefalexin, enro- mecA-positive and multidrug-resistant reflection paper on the risk of antimi- with colonisation of small animals with
floxacin, clindamycin and trimethoprim/ strains is worrying. Several meticil- crobial resistance. The document points this pathogen1. In Europe, the main cir-
sulfamethoxazole2,6,26. One report evaluated lin-resistant staphylococci (MRS) clonal out that MRSA, MRSP, extended-spec- culating clones are ST71-SCCmec II-III
the trends and molecular mechanisms lineages circulating in human hospitals trum ß-lactamases (ESBL, ampC ) and ST106-SCCmec IV 6, 30.
and in the community were found in producing Enterobacteriaceae and
SYNOPSIS

SYNOPSIS
of antimicrobial resistance in clinical In Europe, acquired ampicillin resistance
staphylococci isolated from companion this study, suggesting that companion multidrug-resistant non-fermenting
animals can become accidently infect- is a major phenotypic marker of hospital
animals over a 16-year period6. In- Gram-negative bacteria have emerged
ed with highly successful human MRS acquired Enterococcus faecium and
creasing resistance trends to the above in both healthy and sick dogs and cats13.
clones or may indicate that these clones experience has shown that the appear-
antimicrobials were also observed, A potential risk of transmission of these
are not host specific. ance of such resistance often precedes
but also to cefoxitin in S. aureus and bacteria to humans from infected or col-
increasing rates of vancomycin resistant
CoNS, oxacillin in S. pseudinterme- onized companion animals is implied. In
Thus, companion animals can act enterococci (VRE) with a delay of several
dius, and to amoxicillin-clavulanate, addition there is the possibility of trans-
as reservoirs of important bacteri- years. Ampicillin resistance and also
cefotaxime, ceftriaxone, ciprofloxacin, fer of genetic material coding for re-
al clones and genes of human origin, high level gentamicin resistance has
norfloxacin, ofloxacin, moxifloxacin, sistance from companion animals. The
perpetuating the transmission cycle of been detected in Enterococcus faecalis
tetracycline, chloramphenicol, gentamicin, occurrence of multidrug resistant bac-
MRS. teria (e.g. MRSA, MRSP, ESBLs) in com-
panion animals poses a serious threat
to animal health and welfare due to the
lack of treatment options and treatment
failure that could lead to the euthanasia
Meticillin resistant of the animal3 – besides being a public
Staphylococcus health risk to those in contact with the
Penicillin resistant
Susceptible Staphylococcus Resistance to animal3,8,13,38.
amoxicillin,
Staphylococcus Resistance to
cephalexin (1GC), Knowledge of the mechanisms involved
penicillin and amoxicillin.
cefovecin (3GC), in ß-lactam resistance among Gram-
carbapenems. positive and Gram-negative bacteria
Figure 2 - Stepwise mechanisms of ß-lactam resistance to meticillin resistance in Staphylococcus may be very useful when choosing anti- Multidrug resistant bacteria pose a serious
mediated by the mecA gene (resistance is mediated by the mecA gene that encodes penicillin microbial therapy (Figure 2). threat to animal health and welfare due to
binding protein 2a). the lack of treatment options and a public
Meticillin-resistant staphylococci (MRSA, health risk to those in contact with the
MRSP) have been reported in companion animal.
animals with UTI in Europe4, 6. MRSP

466 467
Current situation of antibiotic resistance in dogs and cats,
emerging resistance patterns

causing UTI11. Clones of resistant the treatment options of AREF infec- clone in humans which is now being reported in Germany36. An OXA-23-
enterococci bacteria associated with tions are limited to penicillin or penicil- detected in companion animal with UTI33. mediated carbapenem resistance in
nosocomial infections in humans have lin/gentamicin combinations and, as a Carbapenem resistance has so far re- sequence type 2 multidrug-resistant
been isolated with increased frequency in last resort, vancomycin10. The potential mained a rare phenomenon among Acinetobacter baumannii was associated
healthy pets; Damborg et al10 described reservoir role of pets for resistant bacte- Gram-negative bacteria isolated from with UTI in a cat in Portugal32. It is
the first isolates of ampicillin resistant ria, even those of human origin, should companion animals in Europe. Car- believed that carbapenemase resist-
E. faecium ST-192 (AREF) that were all not be ignored10,18. bapenems are not commonly used in ant Gram-negative bacteria are likely
similar to the human clonal complex 17 ESBL producing organisms have been small animal practice and should be from human origin, as these drugs are
(CC17). This poses a serious risk for an- identified in companion animals. The avoided as these are considered “last commonly used as last resort to treat
imal health, as E. faecium is a common majority of isolates in these studies resort” drugs in human medicine46. multidrug resistant life-threatening in-
pathogen in canine UTIs and is resist- were E. coli isolated from UTIs, name- Carbapenems are not licensed for fections in hospital settings46. New Del-
SYNOPSIS

SYNOPSIS
ant to commonly used antimicrobials ly the CTX-M-15-producing E. coli 12,14,20. veterinary use, although off-label use hi Metallo-ß-Lactamase (blaNDM) in E.
for the treatment of this condition (e.g. This multidrug-resistant ESBL produc- has been reported occasionally asso- coli isolates have also been recently de-
ampicillin, potentiated amoxicillins and ing E. coli (resistance to 3GC, aminogly- ciated with the treatment of infections tected in diseased small animals in the
sulphonamides, first generation ceph- cosides and fluoroquinolones) belongs caused by multidrug resistant path- USA posing issues for animal and public
alosporins, 3GC and fluoroquinolones)10. to the sequence type 131 and has re- ogens in these species42. Recently, health due to potential treatment failure
This is a potential public health risk, as cently emerged as a worldwide pandemic the emergence and clonal spread of due to lack to therapeutic options for
K. pneumoniae and E. coli producing both animals and humans in the close
carbapenemase OXA-48 in dogs was community35. n

Available data show that resistant bacteria emerge in


companion animals and several problematic multidrug
resistant organisms are shared between companion animals
and humans. Thus the use of antimicrobials in companion an-
imals contributes to the selection and potential spread of drug resistance
which constitutes a potential risk to public health.

Pets can become colonised or infected with resistant strains by food and treats of animal origin.

468 469
Relevance of multidrug-resistant infections
for the veterinary professional

S
enior healthcare leaders through- Figure 1). This does not take into account (MRSP). MRSP was first recognised
out the world have raised concerns the increased morbidity and costs asso- in Europe and North America in 2004,
about the danger antimicrobial ciated with successful treatment and/or and has spread in domestic animals
resistance poses to modern health- avoiding procedures where the risk of throughout Europe, USA and Canada.
care. The World Health Organisation infection is too high. The impact on vet- Meticillin-resistant staphylococci have
considers that this is one of the great- erinary healthcare is likely to be similar- been isolated from 0.5% to 10% of vet-
est threats that we are facing. This was ly devastating. visiting animals and clinical samples in
highlighted by the recent award of the Europe and Canada, but the prevalence
UK Longitude Prize to research in this The first companion animal MRSA iso- can be higher. The prevalence was 46%
field, with Catherine Ball of the Bio- lates were also reported in 1961, with among canine in-patients in Japan, and
chemical Society stating that “antibiotic multiple case series emerging in the in the US they were found in 15-38% of
SYNOPSIS

SYNOPSIS
resistance is the obvious choice” [for the Humans and animals are exposed to the 1990s. Meticillin resistance also oc- dogs with pyoderma and up to 20% of
same drugs, bacteria and resistance genes. curs in other staphylococci including
award]; indeed, without antibiotics many As they are often in close contact, bacteria clinical samples.
of the discoveries in the other challenge can be transferred in both directions.
Staphylococcus pseudintermedius
areas could be rendered useless.

How real is the threat from antimicrobial resis-


tance?
Evidence of clinically significant antimi- if we did not see antimicrobial resist-
crobial resistance in human healthcare ance in veterinary healthcare.
is clear. The One Health Initiative recog-
nises that humans and animals are in- The development of antibiotic resistance
was inevitable as antibiotic resistance
timately associated: we are exposed to
genes are widespread in nature. Antibi-
the same drugs, bacteria and resistance
otics favour the survival of bacteria car-
genes. Humans and animals are often
rying resistance genes, allowing them
in close contact and bacteria can be
to spread. Resistance to penicillins
transferred in both directions. For ex- was seen shortly after the introduction
ample, identical bacteria can be isolated of these drugs; for example, meticil-
from humans and animals in the same lin was introduced in 1959 and MRSA
households, dog owners can become first isolated in 1961. Since then, the
colonised with bacteria from their dog’s prevalence of antimicrobial resistance
pyoderma, and in-contact humans carry has increased, and it is estimated that Figure 1 - Estimates of current and future human deaths attributable to antimicrobial infections
equine and farm animal specific MRSA this will result in an annual toll of 10 (From: Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the
strains. It would therefore be surprising Health and Wealth of Nations. 2014.).
million deaths worldwide by 2050 (see

470 471
Relevance of multidrug-resistant infections for
the veterinary professional

The first case series of MRSA in the UK


were seen in the late 1990s and it be- Does antibiotic use select for resistance?
came a prominent clinical concern in There is no doubt that antibiotic use Greece) (see Figure 2). Reducing anti-
2004. There has been a steady increase is the single biggest factor driving the biotic prescribing in Sweden was asso-
in the prevalence, with one laboratory emergence and spread of antibiotic re- ciated with lower levels of resistance.
seeing the proportion of meticillin-re- sistance. Levels of resistance correlate Glycopeptides, cephalosporins, and
sistance among staphylococcal isolates well with antibiotic prescribing rates in fluoroquinolones have been specifically
increase from 3.8% to 8.9% in 2008- human healthcare (e.g. rates of defined associated with selection for MRSA in
2012. However, this overall figure masks daily doses per 1,000 people/day of 11.4 humans.
a subtle shift in the epidemiology of in the Netherlands compared to 28 in
meticillin-resistant staphylococci. Over
SYNOPSIS

SYNOPSIS
this period the number of MRSA iso- Fluoroquinolone-resistant, ESBL and AmpC
lates has been relatively stable and the producing E. coli have been found in 5-10%
increase in prevalence is accounted for of faecal and environmental samples from
by MRSP isolates (which have increased veterinary hospitals in the UK.
from 7.1% to 64.2% of the total). MRSP
isolates are of concern as they have a
wider resistance spectrum than MRSA Other bacteria of concern showing an
isolates, and are more host-adapted to Percentage resistance
increasing prevalence of antimicrobial
and persistent in animals. resistance include multidrug-resistant < 1%
(MDR; resistance to ≥3 antimicrobial 1 to < 5%
classes) Pseudomonas, Salmonella and 5 to < 10%
Streptococcus, and extended spectrum 10 to < 25%
ß-lactamase (ESBL) and AmpC produc-
25 to < 50%
ing E. coli and Klebsiella. For example,
fluoroquinolone resistant, ESBL and ≥ 50%
AmpC producing E. coli have been found No data reported or
in 5-10% of faecal and environmental less than 10 isolates
samples from veterinary hospitals in the Not included
UK.

Liechtenstein
Luxembourg
Malta
Figure 2 - Proportion of MRSA human isolates in Europe in 2014 (source: European Centre for
Meticillin-resistant staphylococci (MRSA) Disease Prevention and Control, ECDC).

472 473
Relevance of multidrug-resistant infections for
the veterinary professional

It is therefore not surprising that the two than animals with community acquired ESBL and AmpC E. coli can be isolat-
main risk factors for infection or coloni- 100 wounds and infections. ed from 5-10% of ward floor, table and
mecA
sation with antibiotic resistant bacteria 90
MDR staph keyboard samples.
in animals are contact with veterinary 80
MDR E. coli
Studies have shown that 7-13% of vet-
environments and multiple antibiotic 70 ESBL E. coli erinary staff are colonised with meti- It is therefore likely that most colonisa-
courses. Studies of antimicrobial use 60 cillin-resistant staphylococci, and that tion and infection with antibiotic resist-
in veterinary practices show that some
50 these isolates reflect their area of work. ant bacteria is associated with veter-
25% of dogs and 17% of horses receive
40
Meticillin-resistant staphylococci can inary contact and treatment. The risks
antimicrobials, with broad-spectrum drugs
30
also be isolated from up to 10% of en- of this can be reduced by adopting re-
20
the most commonly prescribed antimi- vironmental samples in veterinary prac- sponsible antimicrobial use policies and
10
crobials in both species. Systemic anti- 0
tices, particularly hand touch sites, and adhering to strict infection control.
SYNOPSIS

SYNOPSIS
Before End of Month 1 Month 2
microbial treatment in dogs increases treatment treatment
the prevalence of antimicrobial resist- Figure 3 - Prevalence of antimicrobial resis- Key professional responsibilities
ance among commensal staphylococci tance (%) among commensal staphylococci Veterinarians must exercise great-
and E. coli, and the effects generally last and E. coli in dogs treated with systemic
antibiotics (MDR, mecA, ESBL). Data from er antimicrobial stewardship. Recent
for three months after the end of treat-
Dr Vanessa Schmidt and Dr Nicola Williams, studies found that only 3.5% of small
ment (Figure 3). However the evidence The University of Liverpool School of Veteri- animal practices and 0.8% of equine
that specific antimicrobials particularly nary Science.
practices in the UK had an antimicrobi-
select for resistance is less clear.
al use policy. These are key to helping
veterinarians use these drugs less often
and more effectively, thereby preserving
Where do animals become colonised and infec- their efficacy for the future. A variety of
antimicrobial use guidelines have been
ted? produced (see further resources) for
Antibiotic resistance genes are natural Clinically significant antimicrobial resist- practice use. Similarly, improving hand
and widespread in the environment. ant bacteria are much less common in hygiene and infection control measures
Antibiotic resistant bacteria can also healthy community based animals. ESBL E. have reduced colonisation and infection
be isolated from healthy animals in the rates in human and veterinary health- Regular clinical audit is essential to monitor
coli are only carried by 6.3% of horses and trends in antimicrobial resistance and iden-
community. For example, nearly 40% of 4% of dogs, and AmpC E. coli, MRSA and care. It is essential that veterinary prac- tify potential problems.
healthy horses and 18-29% of healthy MRSP by less than 1% of animals. Coloni- tices adopt and adhere to strict infection
dogs carry MDR E. coli, and 29% of sation with antimicrobial resistant bacteria control guidelines. Guidance to help and improving measures to counter these.
horses and 6-40% of dogs carry meticil- increases with veterinary contact, particu- veterinary practices develop their infec-
lin-resistant coagulase-negative staph- larly hospitalisation, surgery and systemic tion control measures is available from Responsible antimicrobial use is now
ylococci (MR-CoNS). The clinical sig- antimicrobials. Animals that have had mul- several sources (see further resources). considered a professional responsibili-
nificance of these isolates is uncertain; tiple antibiotic courses and/or have post-op- Regular clinical audit to monitor trends ty by the UK Royal College of Veterinary
they are rarely isolated from infections erative or nosocomial (healthcare-associ- in antimicrobial resistance and hospital Surgeons (RCVS). Effective infection
although they may act as reservoirs of ated) infections are significantly more likely acquired infections is vital in identifying control is also a key part of the RCVS
resistance genes. to have antimicrobial resistant infections potential problems in infection control Practice Standards Scheme. While most

474 475
Relevance of multidrug-resistant infections for
the veterinary professional

practices will encounter occasional anti- However, practices that do not adopt ap-
microbial resistant infections, wound propriate antimicrobial use guidelines
breakdowns, and/or hospital acquired and infection control measures or that
infections it is unlikely that these would cannot document this could be consid-
be regarded as negligent provided that ap- ered negligent with all the consequenc-
propriate measures have been taken and es that this entails. n
adherence to these can be documented.

Antibiotic resistance is a clear threat to modern veterinary


SYNOPSIS

SYNOPSIS
healthcare. New drugs are not the answer; if we do
not learn to use antimicrobials more wisely we will at
best merely push the problem forward for a few years.
We can help by improving infection control, reducing antimicrobial use,
and using these drugs more effectively. We should encourage owners to
expect less antibiotic treatment and to follow instructions carefully when
they are prescribed. Finally, we can work with policy makers to develop
effective guidelines and regulation to further responsible antimicrobial
use without compromising animal welfare.

Further resources for antimicrobial stewardship and infection control

• British Veterinary Association -


www.bva.co.uk/public/documents/bva_antimicrobials_poster.pdf
• British Small Animal Veterinary Association -
www.bsava.com/Advice/PracticePack/PROTECTPoster/tabid/1500/Default.aspx
www.bsava.com/Resources/MRSA.aspx
• British Equine Veterinary Association - www.beva.org.uk/useful-info/Vets/Guidance/AMR
• Responsible Use of Medicines in Agriculture (RUMA) - www.ruma.org.uk
• Federation of European Companion Animal Veterinary Associations (FECAVA) - www.fecava.org
• International Society for Companion Animal Infectious Diseases (ISCAID) – www.iscaid.org
• Bella Moss Foundation - www.thebellamossfoundation.com
• Infection control guidelines - www.thebellamossfoundation.com/practice-guidelines/
• Antibiotic treatment support materials and other resources -
www.itsinfectious.co.uk
• Antibiotic Action and Antibiotic Guardian campaigns -
http://antibiotic-action.com/ and http://antibioticguardian.com/

476 477
Tables comparing existing
guidelines

Disorder Summary Europe (FECAVA) UK (BSAVA) Denmark (SvHKS) France (AFVAC) International (ISCAID) Vet. Rec. 2013

Skin and ear disorders


1st choice:
Cytology, Culture & Lincosamides
sensitivity testing (clinda or linco). 1st choice:
if possible. 1GC 1GC (cefalexin,
Cyto, C&ST (cefalexin, cefadroxil). cefadroxil). Amoxi-clav
C&ST
Topical AS if possible. Amoxi-clav. Lincosamides
Cyto, C&ST in case of failure
(chlorhexidine…). Topical AS (clinda or lincomycin).
if possible. Topical AS: 1. Topical AS 1st or 2nd choice:
Topical AB chlorhexidine. generally suffice for (no consensus). 3GC
Superficial Clinda, (shampoo).
SYNOPSIS

SYNOPSIS
(fusidic acid, SF). superficial pyoderma 3GC (cefovecin,
pyoderma or cefalexin or TMPS. Topical AB, 2. Amoxi-clav,
Systemic ABs fusidic acid, SF. 1. Clinda. (cefovecin, cefpodoxime)
cefalexin (BID) or
(different according 2. Cefalexin (cefa- cefpodoxime). can be 1st choice AB
General fusidic acid.
to countries). droxil), amoxi-clav, 2nd choice: if administration
antibiotherapy: 3. Clinda or TMPS proves difficult.
1st choice: 1GC amoxi-clav, cefalexin, TMPS, doxy. (after 1st choice and
(cefalexin, cefadroxil), cefadroxil, clinda, C&ST). 2nd choice:
amoxi-clav, TMPS, cefovecin Tetracyclines (doxy), FQ (enro, marbo, orbi,
clinda. (if compliance chloramphenicol, pradofloxaxin)
2nd choice: problems). FQ (enro, marbo, or 3GC
FQ (enro, marbo, orbi, pradofloxaxin), (cefovecin,
FQ (2nd intention). aminosides (genta or cefpodoxime).
prado…), aminosides,
TC (doxy). MRSA, MRSI: amikacin), ± TMPS, ± 3rd choice:
depending on C&ST Cyto + C&ST. lincosamides (clinda).
No consensus on 3GC aminosides, azithro,
Cyto, C&ST. or chlorhexidine, 1. Clinda. Topical AS + 3rd choice: clarithro, ceftazidime,
(cefovecin). fusidic acid, Amoxi-clav,
Cefalexin 2. Cefalexin (if 1st and 2nd choice chloramphenicol,
Deep AB reserved for doxy, TMPS. (cefadroxil), cefalexin (BID), fusidic inappropriate florfenicol,
human medicine: (while awaiting acid, clinda or TMPS.
pyoderma C&ST results). amoxi-clav, and after C&ST). thiamphenicol,
not recommended. TMPS, doxy, In case of failure AB reserved for rifampicin,
In case of MRSA or and after C&ST, FQ. human medicine: piperacillin,
MRSI: alternative AS, 3. FQ or 3GC
(cefovecin). linezolide, ticarcillin, imipenem.
fusidic acid… teicoplanin,
vancomycin.

478 479
Tables comparing existing guidelines

Disorder Summary Europe (FECAVA) UK (BSAVA) Denmark (SvHKS) France (AFVAC) International (ISCAID) Vet. Rec. 2013

Skin and ear disorders


Cyto (+ C&ST in case
Cleaning and of surgical
disinfection of complication and/or
wounds, in general suspicion of ESBL,
without topical AB. MRSA, MRSI). Topical
Wound, AB not routinely
Systemic ABs not Amoxi-clav. As above
abscess, recommended.
recommended if no or 1GC (cefalexin) (deep pyoderma)
soft tissue general clinical signs Cleaning and or FQ (2nd choice). if AB necessary.
SYNOPSIS

SYNOPSIS
infection (fever) or severe disinfection of the
infection. wounds.
AB if necessary: In case of fever or
see above. severe infection,
systemic AB.

Cyto + C&ST
Ceruminous otitis: if possible.
Topical: fusidic Otitis due to cocci
No systemic ABs. Cyto without C&ST. acid, framycetin, (or mixed infections):
Topical AS or AB Systemic ABs not genta; marbo, orbi, Fusidic acid and
If cocci: fusidic acid needed. polymyxin B, framycetin, or genta.
or other. miconazole Otitis due to bacilli
Topical AS or fusidic + cleaning.
Otitis externa If bacilli: polymyxin B, (except
acid (cocci), or
FQ, or aminosides Suppurative otitis: Pseudomonas):
polymyxin B (bacilli).
(genta). Topical: FQ or polymyxin B, genta
Anti-Malassezia Anti-Malassezia or marbo.
aminoside.
ttm+ corticoids. ttm+ corticoids. Pseudomonas:
idem + FQ or genta by
systemic route if
severe infection.

480 481
Tables comparing existing guidelines

Disorder Summary Europe (FECAVA) UK (BSAVA) Denmark (SvHKS) France (AFVAC) International (ISCAID) Vet. Rec. 2013

Skin and ear disorders


Wounds with Skin surgery
granulation tissue. (mass excision)
Deep or superficial without major
pyoderma. reconstruction.
Systemic AB not Hyperseborrheic Dermatitis due to
recommended skin disorder, Malassezia,
Otitis externa, pruritus,
Uncomplicated desquamation,
SYNOPSIS

SYNOPSIS
wounds and lesions. nodules, crusts.
Cat-bite abscess.

Urinary disorders
Cyto + C&ST
Cystitis Cat/Dog: Dogs (no C&ST if
(if recurrence). Cyto + C&ST Amoxi or TMPS
Amoxi-clav or TMPS. Cyto + C&ST. uncomplicated):
Lower urinary Amoxi-clav or TMPS (if recurrence).
amoxi-clav, cefalexin (while awaiting
UTI often not Cat/Dog: Amoxi or
tract infection Cat: non-infectious Amoxi-clav or TMPS or TMPS. C&ST results if
infectious in cats. TMPS (while awaiting
(cystitis or UTI) UTI: AB not (while awaiting complicated
Struvite dogs: C&ST results). Cats according infection).
recommended C&ST results).
Amoxi-clav or TMPS. to C&ST.
(or after C&ST).
Cyto + C&ST Cyto + C&ST
(cystocentesis). (cystocentesis). TMPS (and C&ST in Cyto + C&ST Cyto + C&ST
Upper urinary Amoxi-clav, TMPS Amoxi-clav or chronic cases). (cystocentesis). (cystocentesis). Pyelonephritis:
tract infection, or FQ while awaiting FQ while awaiting Suspicion of Amoxi-clav or Amoxi-clav, FQ while awaiting
Pyelonephritis C&ST results. C&ST results. Leptospira: ampi, FQ while awaiting FQ, TMPS, C&ST results.
In case of general In case of general amoxi, peni G, doxy. C&ST results. nitrofurans.
signs, see sepsis. signs, see sepsis.
Subclinical Antibiotic prevention
No ABs recommended AB not
bacteria, Urinary in case of catheter is
if no clinical signs. recommended.
catheterism contra-indicated.
Urinary incontinence.
Systemic AB not Feline urolithiasis.
Feline urolithiasis.
recommended Metabolic disease
(polyuria/polydipsia…).

482 483
Tables comparing existing guidelines

Disorder Summary Europe (FECAVA) UK (BSAVA) Denmark (SvHKS) France (AFVAC) International (ISCAID)

Genital disorders
Castration.
Orchitis and Castration. Amoxi-clav or TMPS.
epididymitis Amoxi-clav or TMPS. (+ Brucellosis
serology).

C&ST if possible. FQ or TMPS. C&ST if possible.


Prostatitis FQ or TMPS + C&ST in Enro or TMPS FQ, TMPS. FQ, TMPS.
SYNOPSIS

SYNOPSIS
+ Castration. chronic cases + Castration.

C&ST if possible.
Amoxi-clav. C&ST if possible.
Mastitis Amoxi, amoxi-clav
or TMPS. Amoxi.
or TMPS.

C&ST if possible. C&ST if possible.


In case of general
Acute metritis In case of general signs: amoxi-clav In case of general
signs: amoxi-clav or TMPS. signs: amoxi-clav
or TMPS. or TMPS.

C&ST if possible.
C&ST if possible.
1. TMPS or Amoxi-clav
Endometritis 1. TMPS
amoxi-clav or TMPS.
2. Enro
2. FQ.

Medical treatment
Medical treatment
(aglepristone and Pg)
(aglepristone and Pg) Surgical treatment. and in severe cases:
and in severe cases:
Pyometra In severe cases, FQ. Amoxi-clav or TMPS. TMPS or enro.
TMPS or FQ.
Surgical treatment
Surgical treatment
with perioperative AB
with perioperative AB.
(ampicillin IV).

Juvenile vaginitis,
Systemic AB not Balanoposthitis,
recommended Prostatic hyperplasia
(or cysts).

484 485
Tables comparing existing guidelines

Europe UK Denmark Europe UK Denmark


Disorder Summary Disorder Summary
(FECAVA) (BSAVA) (SvHKS) (FECAVA) (BSAVA) (SvHKS)
Respiratory diseases Respiratory diseases
AB not Cyto + C&ST
recommended. (thoracocentesis).
AB not Except chronic Drainage and Cyto + C&ST
recommended. purulent rhinitis: If necessary lavage of the (thoracocentesis).
Except chronic (doxy). pyothorax. Drainage and
Rhinitis Amoxi-clav. 1. Doxy. Cyto + C&ST
purulent rhinitis: No C&ST, but In case of cocci: lavage of the
doxy or amoxi/ 2. Amoxi. amoxi-clav (or pyothorax. (thoracocentesis).
look for the (non Dog: Ampi + FQ,
amoxi-clav. infectious) cause ampi IV) or other. Drainage and
SYNOPSIS

SYNOPSIS
In case of cocci: clinda + FQ, lavage of the
of the chronic Pyothorax In case of bacilli, amoxi-clav metronid + FQ. pyothorax.
purulent rhinitis. FQ (while waiting q8 hours. Cat: Amoxi-clav.
for the C&ST FQ (enro) + Ampi
No AB unless results). In case of bacilli (IV route).
In severe cases: AB if FQ (while waiting
fever. Association to
AB not amoxi-clav, doxy complication for the C&ST
In case of recommended. or OTC. (fever): large spectrum results).
Acute complication: AB (FQ +…) while
No C&ST In case of my- 1. doxy (active
bronchitis doxy or waiting for the
(commensal coplasm: azithro, against
amoxi-clav. C&ST results.
flora). doxy or OTC mycoplasm).
In case of (dogs). 2. Amoxi. Kennel cough,
mycoplasm: doxy.
Systemic AB Chronic
C&ST is difficult bronchitis,
not
(BAL). No C&ST Viral disease,
(sampling is recommended
Amoxi-clav/ Dog: aminosides C&ST viral rhinitis and
ampi IV route (or difficult, BAL). + metronid, amoxi cat flu.
recommended.
cefalexin, doxy…) Doxy, cefalexin, + FQ, amoxi
+ metronid, doxy 1. Amoxi-clav (or
Pneumonia ± metronid. amoxi-clav (TID).
or OTC ampi IV route).
In severe cases In severe cases:
Cat: amoxi-clav 2. FQ (enro)
(large spectrum): FQ + Peni G/
or doxy. + ampi (IV route).
FQ + Peni G/ amoxi/ ampi (IV
amoxi/ ampi (IV route).
route).

486 487
Tables comparing existing guidelines

Europe UK Denmark Europe UK Denmark


Disorder Summary Disorder Summary
(FECAVA) (BSAVA) (SvHKS) (FECAVA) (BSAVA) (SvHKS)
Digestive, hepatic and oral diseases Digestive, hepatic and oral diseases
No AB. Prednisolone Prednisolone Prednisolone
alone. alone. alone.
No AB. C&ST
recommended Chronic If necessary: If necessary: If necessary:
Oral infection In case of No AB. Ampi, amoxi, in case of AB association association association
systemic signs enteropathy
(gingivitis, In case of amoxi-clav. therapy. with tylo with tylo with tylo
stomatitis, (fever…): clinda, clinda, spira (or failing that, (or failing that, (or failing that,
systemic signs In case of
spira + metronid, + metronid. TC or metronid). TC or metronid). TC or metronid).
periodontitis) ampi/ amoxi/
(fever…): clinda. systemic signs
(fever…): clinda
SYNOPSIS

SYNOPSIS
amoxi-clav. No systemic AB.
(second choice: No AB. No AB.
amoxi/clav). In case of severe
In case of severe In case of severe
infection: Topical
Anal gland infection: infection:
No AB if no cyto + C&ST treatment.
Acute No AB unless abscess cyto + C&ST cyto + C&ST
clinical signs + TMPS or
complicated C&ST. + TMPS (while Amoxi-clav. + TMPS (while
(see sepsis). amoxi-clav while
diarrhoea: waiting for the waiting for the
C&ST if waiting for the
Specific amoxi-clav or C&ST results). C&ST results).
suspicion of C&ST results.
gastro-enteritis cefalexin. Salm. or
(culture). Gastro-enteritis Campylob. or Cyto + C&ST
Campylob: with blood:
Liver infection
No AB toxigenic Clost. (if possible, Cyto + C&ST Ampi, amoxi, Cyto + C&ST
macrolides metronid (cholecystitis, biopsy or FNA). (if possible, (if possible,
if no Campylob: amoxi-clav.
(FQ ?). + (amoxi-clav or cholangitis, biopsy or FNA). biopsy or FNA).
clinical signs erythro or tylo. Ampi/ amoxi/ cefalexin,
Cl. difficile: cefalexin) ± FQ cholangio- metronid.
(see sepsis). Cl. difficile: amoxi-clav/ Doxy or cefalexin. Doxy or cefalexin.
Gastro- metronid. or aminosides hepatitis) cefalexin or doxy.
C&ST if against Gram metronid.
enteritis Cl. perfringens: suspicion of negative agents. Cl. perfringens:
tylo or metronid. Salm. or
Campylob.: tylo or metronid.
Salm. after Campylob. or
enro or erythro. Salm. after
C&ST. toxigenic Clost.
Helicobacter C&ST.
Gastritis
gastritis: Gastritis
resistant to
amoxi + metronid, resistant to other
other treatments
azithro + tindizole, treatments:
(Helicobacter):
clarithro + metronid omeprazole,
omeprazole,
(+ antiulcer amoxi + metronid
amoxi + metro
treatment). (or clarithro).
(or clarithro).

488 489
Tables comparing existing guidelines

Europe UK Denmark Europe UK Denmark


Disorder Summary Disorder Summary
(FECAVA) (BSAVA) (SvHKS) (FECAVA) (BSAVA) (SvHKS)
Digestives, hepatic and oral diseases Sepsis and general diseases
Chronic Cyto + C&ST
inflammatory (paracentesis). Cyto + C&ST Amoxi-clav, ampi
enteropathy. (paracentesis). + FQ or genta or
While waiting
Anal sacculitis for the C&ST FQ + Peni G/ cefotaxime,
without abscess. Peritonitis results, large amoxi/ ampi (IV) Or clinda + enro.
Parodontal spectrum: FQ while waiting + metronid if
disease. Acute diarrhoea + ß-lactams/ for the C&ST
Systemic AB anaerobes
Viral or vomiting, clinda/ metronid results. suspected.
SYNOPSIS

SYNOPSIS
not gastroenteritis (if anaerobes).
(parvo), Chronic
recommended
gastroenteritis. Cyto + C&ST
Gastroenteritis Cyto + C&ST on
due to (several blood Cyto + C&ST on
several blood
Salmonella, samples). Amoxi-clav + FQ, several blood
samples.
Campylobacter While waiting ampi + FQ samples.
or Cl. difficile. Sepsis FQ + Peni G/ or genta
for the C&ST Enro + ampi (IV)
Routine dental amoxi/ ampi (IV) or cefotaxime,
results, large while waiting
descale. while waiting clinda + enro.
spectrum: FQ for the C&ST
for the C&ST
+ ß-lactams/ results.
results.
clinda.
Mild neutropenia:
No AB.
Severe
neutropenia
without clinical
signs:
Neutropenia See UK.
TMPS.
Severe
neutropenia with
clinical signs:
1GC (cefalexin)
+ FQ.
Amoxi-clav
+ enro
Endocarditis See UK.
or amoxi-clav
+ metronid.

490 491
Tables comparing existing guidelines

Europe UK Denmark Europe UK Denmark


Disorder Summary Disorder Summary
(FECAVA) (BSAVA) (SvHKS) (FECAVA) (BSAVA) (SvHKS)
Sepsis and general diseases Eye diseases
Hemobartonellosis: Topical
No systemic AB cloxacillin,
doxy or FQ. Anaplasma spp.: Topical.
Topical AS or AB. fusidic acid,
Anaplasma spp.: 1. doxy; Cat, if
Conjunctivitis Cat, if genta.
1. doxy; 2. rifampicin Chlamydophila,
2. rifampicin or enro. Chlamydophila: Cat, if
doxy.
Vector-borne or enro doxy (± FQ). Chlamydophila,
Hemobartonellosis: Ehrlichiosis:
doxy or enro.
diseases Ehrlichiosis: doxy or FQ. 1. doxy;
1. doxy; 2. imidocarb. Topical.
SYNOPSIS

SYNOPSIS
2. imidocarb. Blepharitis, No systemic AB.
Borreliosis: 1. Fusidic acid.
1. doxy; non-ulcerative
Borreliosis: See Denmark. 2. Chloram-
1. doxy; 2. amoxi. keratitis
phenicol.
2. amoxi.
No systemic AB. If necessary,
Healthy animals Dacryocystitis chloramphenicol
Cardiovascular See Denmark. eye drops.
without contact
disease.
Systemic AB to sick animals. If ulcer with risk
not Metabolic
Viral disease of perforation:
disease
recommended (FeLV, FIV...) chloramphenicol
(polyuropolydipsia,
or non-infectious (drops)
weight loss).
disease. + amoxi-clav
Corneal ulcer See Denmark. (per os).
Melting ulcers:
FQ (cipro) and
amoxi-clav
per os.
AB if necessary
(depending on
Uveitis See Denmark. diagnosis).
Chloramphenicol
eye drops.
C&ST
Retrobulbar recommended
and eye See Denmark. Clinda while
infection waiting for the
C&ST results.

492 493
Tables comparing existing guidelines

Europe UK Denmark Europe UK Denmark


Disorder Summary Disorder Summary
(FECAVA) (BSAVA) (SvHKS) (FECAVA) (BSAVA) (SvHKS)
Bone and joint diseases Surgery
Cyto + C&ST Cyto + C&ST Cyto + C&ST Risk ASA 1-2 with
(FNA of the (FNA of the (FNA of the clean surgery:
No antibiotics. Routine dental
synovial fluid or synovial fluid synovial fluid
Examples: descale,
Septic biopsy). or biopsy). Amoxi-clav or or biopsy).
Routine dental caesarean
arthritis Joint lavage. Joint lavage. 1GC (cefalexin). Joint lavage.
descale, section,
Clinda, or Clinda, or Clinda, castration, laparotomy,
cefalexin, or cefalexin, or or cefalexin, caesarean Routine surgical
Surgery not excision of Risk ASA 1-2
amoxi-clav. amoxi-clav (TID). or amoxi-clav. section, castration,
SYNOPSIS

SYNOPSIS
non-infected with clean
requiring laparotomy, skin surgery
tumours, clean surgery:
X-ray and C&ST perioperative fxcision of (mass excision)
(non-infected) No antibiotic
(bone biopsy). X-ray and C&ST X-ray and C&ST AB non-infected without major
orthopaedic prophylaxis.
(bone biopsy). (bone biopsy). tumours, clean reconstruction
Look for the surgery < 90 min,
(non-infected)
underlying cause Look for the Look for the orthopaedic reconstructive
(e.g. implant…). underlying cause Amoxi-clav or underlying cause surgery < 90 min, skin surgery on
Osteomyelitis
Clinda, (e.g. implant…). 1GC (cefalexin). (e.g. implant…). reconstructive healthy tissue,
amoxi-clav, Clinda while Clinda while skin surgery on neurosurgery.
cefalexin while waiting for the waiting for the healthy tissue,
waiting for the C&ST results. C&ST results. neurosurgery.
C&ST results. Most commonly: Only if risk ASA
AB required if: amoxi-clav or ≥ 3 or infected
Animal already 1GC (cefalexin), wounds, general
infected, immu- IV route. infection, ortho-
nodepressed, AB required if: paedic surgery.
long surgery long surgery If risk of skin
(> 90 min), invol- (> 90 min), involving infection
ving an implant an implant, sick (Staph and
Perioperative or dental disease. or immunode- Pasteurella):
AB 1. Amoxi-clav/ pressed animal, cefazolin (IV).
ampi (IV), digestive surgery
(genta or FQ), If risk of infection
cefalexin. via the digestive
parodontal
2. Digestive or disease or tract or the
uterine surgery: dental surgery uterus
FQ or genta. (+ metronid), (enterobact.,
3. Parodontal infected wounds enterococci,
disease: metronid. or pre-existing anaerobes):
infection. ampicillin (IV).

494 495
Part 4
Appendices
Appendices

496
Classifications and drug index

Principal pharmacological parameters of antibiotics Antibacterial spectrum of activity of selected


antibiotics
Distribution Elimination Use
ANTIBIOTICS during Aerobic Anaerobic
Skin 1
Lungs 2
Secretions Bone CSF 3
Main pathway pregnancy4 bacteria bacteria
Spectrum Gram + Gram - Gram + Gram - Examples
Amoxicillin ±
clavulanate ++ ++ ++ ++ +++
If infl.
Urinary Yes
Very broad Chloramphenicol

Ampicillin ++ ++ ++ + +++ Urinary Yes Very broad 3rd generation fluoroquinolones


If infl.

++ +++
Very broad 3rd and 4th generation cephalosporins
Cefalexin ++ ++ + If infl. Urinary Yes
Very broad Tetracyclines

Cefovecin* ++ ++ ++ ++ +++ If infl. Urinary Yes Broad Ampicillin, amoxicillin (± clavulanate)


Broad 1st generation cephalosporins
Appendices

Appendices
Clindamycin +++ + +++ +++ + Urinary Yes
Broad Trimethoprim - sulfonamides

Doxycycline ++ ++ ++ ++ - Mixed No Intermediate Aminoglycosides


Intermediate Macrolides, lincosamides
Fluoro-
quinolones* +++ +++ +++ +++ +++ Urinary No
Narrow Penicillins G (or M)

Gentamicin - +/- +/- + - Urinary No Narrow Nitroimidazoles (metronidazole)


Narrow Colistin
With
Metronidazole + + +++ ++ +++ Mixed
precautions For more information, see recommendation R.13.

Spiramycin + ++ +++ +++ ++ Biliary Yes Excellent activity Limited activity


Tetracycline Moderate activity No or negligible activity
Oxytetracycline ++ ++ ++ ++ - Mixed No

Trimethoprim -
sulfonamides ++ ++ +++ + +++ Urinary No
If infl.: in case of inflammation
* In bold: critically important antibiotics.

Notes:
1. Note that tissue diffusion in the skin is poor in case of abscesses.
2. Lungs and other well-irrigated tissue.
3. Cerebrospinal fluid.
4. Based on information established in human medicine and the benefit/risk ratio for veterinary medicine.

498 499
Classifications and drug index

Categorization of systemic antibiotics

Use category Definition and guidance for use Examples Use category Definition and guidance for use Examples

• 1st line antibiotics are antibiotics that • Penicillins • 3rd line antibiotics are antibiotics that
Primary/ are well established with good evidence • 1st generation are of great importance to animal and
of high efficacy and safety. Ideally, they cephalosporins human health especially for the
1st line
should be narrow-spectrum. They are • Amoxicillin±clavulanate treatment of multidrug resistant
Licensed for as potent as 2nd and 3rd line drugs used • Trimethoprim bacteria, and where resistance is more
companion in the appropriate circumstances. sulfonamides likely to occur following use and/or
animals • They should be used wherever • Tetracyclines is of great concern in veterinary and
appropriate and possible. human healthcare. Many of these
• Lincosamides
drugs are not licensed for companion • 3rd and 4th generation
animals, and therefore data on clinical cephalosporins
• 2nd line antibiotics are often Tertiary/ break points, efficacy and safety other than cefovecin
broad-spectrum antibiotics that are may be lacking.
Appendices

Appendices
3rd line • Rifampicin
important for animal and human • They must only be used where there
health, and in which resistance is more Narrow spectrum: • Fosfomycin
is culture evidence to show that 1st or
likely to occur following use and/or • Aminoglycosides 2nd line antibiotics will not be effective
is of greater concern in veterinary • Metronidazole and where topical therapy has been
Secondary/
and human healthcare. • Macrolides ineffective or is not feasible.
2nd line • Critically important antibiotics should • The use of 3rd line drugs must be
Licensed for only be used where C&AST results Broad spectrum: supported by AST, although these
companion or good clinical and epidemiological • Chloramphenicol drugs may be started in life-threatening
evidence indicate that 1st line antibiotics conditions while waiting for the culture
animals will not be effective. Critically important ABs: results.
Wherever possible, the use of 2nd line • Fluoroquinolones
drugs should be supported by C&AST. • Cefovecin (3GC) • Glycopeptides:
• Some antibiotics are classified as vancomycin,
2nd line due to their toxicity, teicoplanin
but not due to their activity • Carbapenems and
(e.g. aminoglycosides). Restricted, • These drugs are vitally important to monobactams
voluntarily human health so should never be used • Oxazolidones:
For more information, see recommendation R.17. in animals. lineazolid
prohibited
• Lipopeptides:
daptomycin
• Riminofenazines:
clofazime
For more information, see recommendation R.17.

500 501
Classifications and drug index

Index of the main antibiotics available in companion


animal medicine
Dosage forms Special warnings/ Dosage forms Special warnings/
Family Antibiotic (companion Recommendations in Family Antibiotic (companion Recommendations in
animals) specific conditions animals) specific conditions
Injectable Risk of cartilage alterations
Benzylpenicillin
ß-lactams solution (IM) in growing dogs (in particu-
Tablets,
Penicillin G Risk of ß-lactam allergy. lar large and giant breeds)
Enrofloxacin Inj. sol. (SC)
Benzylpenicillin + Risk of retinal toxicity in
Inj. sol. (IM/SC)
dihydrostreptomycin cats in case of overdosage.
Fluoro-
quinolones* Critical antibiotics.
Ampicillin Tablets, Risk of cartilage alterations
Marbofloxacin
Risk of ß-lactam allergy. Inj. sol. (SC, IV) in growing dogs (in particu-
Tablets,
Amoxicillin lar large and giant breeds).
Appendices

Appendices
Inj sol. (IM/SC) Tablets,
ß-lactams Pradofloxacin Critical antibiotics.
oral solution
Amino- Risk of ß-lactam allergy.
penicillins Adding clavulanate Risk of calcium binding in
Amoxicillin Tablets Tetracyclines Doxycycline Tablets
(ß-lactamase inhibitor) teeth and bone.
+ clavulanate Inj sol. (SC)
is justified in case of
Spiramycin +
ß-lactamase producing Macrolides Tablets
dimetridazole
pathogens. (+ nitro- See metronidazole.
imidazoles) Spiramycin +
ß-lactams Tablets
metronidazole
1st generation Tablets,
Cefalexin Risk of ß-lactam allergy. Tablets,
cephalosporins Inj sol. (IM)
(1GC) Lincosamides Clindamycin Capsules,
Oral solution.
ß-lactams
3rd generation Risk of ß-lactam allergy. Risk of liver toxicity or
Cefovecin Inj. sol. (SC) Nitro- central nervous system
cephalosporins Critical antibiotic. Metronidazole Tablets
(3GC)* imidazoles toxicity in case of
overdosage.
Risk of keratoconjunctivitis
sicca (KCS) and Gentamicin Inj. sol.
Sulfonamides +/- Tablets,
Trimethoprim nephrotoxicity.
diamino- Inj. sol. (IV, IM, Amino- Neomycin Capsules Risk of kidney toxicity if
sulfonamides Schirmer tear testing is
pyrimidines SC) glycosides administered by injection.
recommended if Framycetin
use > 3 weeks. Tablets
(+ sulfaguanidine)
* In bold: critically important antibiotics.
For more information, see the Synopsis chapters.
* In bold: critically important antibiotics.

502 503
Classifications and drug index

Classification of antibiotics according to


their mechanism of action
Bactericidal antibiotics Bacteriostatic antibiotics

Concentration-dependent Time-dependent Time-dependent


Aminoglycosides Penicillins Macrolides
Fluoroquinolones Cephalosporins Lincosamides
Colistin Nitro-imidazoles Tetracyclines
Sulfonamides
Diaminopyrimidines
Phenicoles
For more information, see the Synopsis chapters.

Classification of bacteria according to


Appendices

Appendices
their GRAM staining
Bacteria that cannot
GRAM positive GRAM negative
be stained by Gram*
Aerobic organisms Aerobic organisms Mycoplasma
Corynebacterium spp. Bordetella spp.
Listeria spp. Brucella spp. Intracelullar organisms*
Staphylococcus spp. Campylobacter spp. Rickettsia
Streptococcus spp. Escherichia coli Chlamydia
Haemophilus spp.
Anaerobic organisms* Klebsiella spp.
Actinomyces spp. Leptospira spp.
Bacteroides spp. Neisseria spp.
Clostridium spp. Pasteurella spp.
Fusobacterium spp. Pseudomonas spp.
Salmonella spp.

Anaerobic organisms*
Borrelia

Intracelullar organisms*
Ehrlichia
* In order to be identified by the laboratory, these bacteria generally require specific sampling, transport and
culture conditions.

504 505
Glossary
1GC 1st generation cephalosporins (e.g. cefalexin, cefadroxyl) AUIC Area Under the Inhibitory Curve: the part of the AUC for which the
3GC 3rd generation cephalosporins (e.g. cefovecin) plasma concentration is above the MIC of the target pathogen.
AUIC = AUC/MIC.
AB Antibiotic(s) (synonym: antimicrobial)
For bactericidal concentration-dependent antibiotics the AUIC ratio
ADM Agar Dilution Method should be at least 125, which corresponds to maintaining plasma
AM Antimicrobial (synonym: antibiotic) concentrations five times higher than the MIC for 24 hours.
AMK Amikacin Area Under the

Concentration (mg/l)
Amoxi-clav / AMC Amoxicillin + clavulanate Inhibitory Curve
Amoxi / AMX Amoxicillin
Ampi / AMP Ampicillin AUIC
AMR Antimicrobial resistance MIC
AMS Antimicrobial susceptibility
AMT Antimicrobial therapy Time
AMU Antimicrobial use Azithro Azithromycin
AS Antiseptics B. fragilis Bacteroides fragilis
Appendices

Appendices
ASA American Society of Anesthesiologists, which defined a widely BALF Bronchoalveolar Lavage Fluid
used classification of anaesthetic risk BID Twice daily (bis in die)
AST Antibiotic Susceptibility/Sensitivity Testing Bioavailability Amount (or fraction F, in %) of an administered dose of drug that
AUC Area Under the Curve: the area under the plasma or blood reaches the systemic circulation. By definition, if a medication is
concentration-time curve, i.e. the total drug expose over time. administered intravenously, its bioavailability is 100%. Bioavailability
It is proportional to the amount of active substance absorbed. is calculated by the AUC between two subsequent administrations.
It is expressed in µg x h / ml or µg /ml x h. Absolute bioavailability is compared to the AUC for IV administration,
e.g. AUCIM/AUCIV.
Area Under the Curve Relative bioavailability compares the AUC to that of another,
Concentration (mg/l)

non-intravenous route, e.g. AUCoral sol. /AUCtablet.


The relative bioavailability between two similar galenic forms is
sometimes based on the Cmax rather than the AUC, e.g.
Cmaxoral sol./Cmaxtablet. Bioavailability also covers the speed with
AUC which the drug reaches the blood (see Cmax and Tmax).
(Clinical) Breakpoint: the concentration of an antibiotic which defines
Time breakpoints whether a species of bacteria is susceptible or resistant to the
antibiotic. If the MIC is less than or equal to the susceptibility
AUC24h AUC for the first 24 hours. breakpoint the bacteria is considered susceptible to the antibiotic.
AUCIV, AUCIM, These are the AUC obtained depending on the route of If the MIC is greater than this value the bacteria is considered
AUCSC, AUCoral administration (see next page for the calculation of the intermediate or resistant to the antibiotic.
bioavailability). For the results of antibiotic sensitivity testing to be predictive of
the therapeutic outcome, clinical breakpoints have been
established according to dosages, pharmacokinetic data,

506 507
Glossary
resistance mechanisms, MIC distributions, zone diameter CLSI Clinical and Laboratory Standards Institute
distributions and pharmacodynamics and epidemiological Cmax/Tmax Cmax: maximum (peak) plasma concentration after administration
cut-off values (ECOFFs). of the antibiotic. The Cmax is reached at a time after administration
C. difficile Clostridium difficile called Tmax (usually between 15 minutes and 6 hours, depending
C&(A)ST Culture and (Antibiotic) Sensitivity/Susceptibility Testing on the formulation and the route of administration).
Cmax and Tmax indicate the speed of absorption in the blood.
CA Companion Animals
They do not apply to intravenous administration, for which
Cascade use Use outside the indications or target species as approved in the absorption is immediate and complete.
SPC
Cmax
CEF Cefalotin Plasma

Concentration (mg/l)
CFF Ceftiofur concentrations
CFO Cefovecin
CFU Colony Forming Units: the number of identified colonies, and is a
measure of viable bacterial cells in the sample. Results are given
as CFU/ml for liquid, CFU/g for solid samples.
CFZ Cefazolin
Appendices

Appendices
Tmax Time
CHL Chloramphenicol Colonisation Development of bacteria in an infected animal, without showing
CIA Critically Important Antibiotic. See also recommendation R.16. clinical signs linked to the infection.
CIP /Cipro Ciprofloxacin CVMP Committee for Medicinal Products for Veterinary Use: committee at
CKD Chronic Kidney Disease the European Medicines Agency.
Cl Clearance: the volume of plasma completely cleared of a Cyto Cytology
substance (antibiotic), per unit of time. The unit is ml/min. Total DCD Defined Course Dose (dosage required for a full course)
body clearance is expressed in ml/min/kg. DDD Defined Daily Dose (assumed average dose per day for a drug
For a substance to be cleared completely after its first passage in used for its main indication)
the circulation, the clearance value equals that of the cardiac flow,
DDM Disk Diffusion Method
which is the maximum clearance value. Different organs can
eliminate the antibiotic, allowing the calculation of several Dose or Antibiotics whose bactericidal activity is linked to the concentration,
difference clearance types: plasma clearance (formerly: body concentration- i.e. to the dose administered. Predictive criteria of concentration
or total clearance), renal clearance, hepatic clearance. dependent dependent antibiotics are the inhibitory quotient (IQ≥8) and the
Renal clearance (Clr) is equivalent to plasma clearance for antibiotics AUIC (≥125).
antibiotics that are completely eliminated via the kidneys.
CFU/mL Concentration-dependent activity
Hepatic clearance (Clh), also called extrarenal clearance (Clnr) is (log10)
2.5 Plasma concentration curves
calculated by subtracting the renal from the total clearance. 2
Control IQ or AUIC
In cattle, this extrarenal clearance also includes elimination in the 9
1 mg/l 1.5
milk and saliva. 2 mg/l 1
7
CLA Clavulanic acid / clavulanate 4 mg/l
0,5
5 8 mg/l
Clarithro Clarithromycin 0
0 20 40 60
CLI/Clinda Clindamycin 3 Time (h) Time (h)
0 2 4 6 24

508 509
Glossary
DOXY / doxy Doxycycline FNA Fine Needle Aspiration
DS Disinfectants FOX Cefoxitin
DSH Domestic Short Hair FOX / CFT Cefoxitin/Cefotetan
E. coli Escherichia coli FQ Fluoroquinolone
ECOFFs Epidemiological cut-off values (ECOFFs) separate bacterial isolates FRA Framycetin
with a high MIC value (with a resistance gene) from susceptible FVE Federation of Veterinarians of Europe
isolates (no resistance gene).
GEN / Genta Gentamicin
40
Sensitive (wild-type) Intermediate Resistant HAI Healthcare-Associated Infections
35 population population population
HPLC High-Performance Liquid Chromatography
30
HPLC / MS High-Performance Liquid Chromatography with Mass Spectrometry
25 EPIDEMIOLOGICAL CLINICAL
Number of CUT-OFF VALUE BREAKPOINT IM intramuscular
20
isolates Infection Animal infected by a pathogen, showing clinical signs related
15 to that infection.
10 IQ Inhibitory Quotient (or inhibitory rate): denoted as the maximum
Appendices

Appendices
5 plasma concentration divided by the minimum inhibitory
0
concentration (Cmax/MIC). For bactericidal concentration-dependent
antibiotics, the IQ should reach 8-10.
02

03

06

13

25

16

32

64

6
0,

12

25
0.

0.

0.

0.

0.

MIC (mg/l) ISB Index of Surviving Bacteria: this indicator measures the bactericidal
EMA European Medicines Agency speed during the early phase, between 0 and 6 hours, based on
bactericidal kinetics measured in vitro. It compares the bactericidal
ENR / Enro Enrofloxacin
AUC to that of the inoculum on a semi-logarithmic scale. The
EPR Electronic Patient Record smaller the ISB (%), the greater the bactericidal action. An ISB
ERT Ertapenem of 0% reflects an intense, dose-dependent bactericidal action,
ERY / Erythro Erythromycin while an ISB of 80% reflects a non-concentration dependent effect.
ESBL Extended-spectrum ß-lactamases (resistance to last generation ISCAID International Society for Companion Animal Infectious Diseases
cephalosporins, including 3GC) IV Intravenous
ESCMID European Society of Clinical Microbiology and Infectious Diseases KAN Kanamycin
ESGAI ESCMID Study Group on Anaerobic Infections KCS Keratoconjunctivitis sicca
ESVAC European Surveillance of Veterinary Antimicrobial Consumption LC/MS Liquid Chromatography with Mass Spectrometry
EUCAST European Committee on Antimicrobial Susceptibility Testing LEX Cefalexin or cephalexin
Extra-label Use other than those described in the SPC, in particular regarding LIN / Linco Lincomycin
drug use indications (cascade use), dosage regimen, contra-indications or LUTD Lower Urinary Tract Disease
warnings.
MAR / Marbo Marbofloxacin
FA Fusidic acid
MBC Minimum Bactericidal Concentration: the lowest concentration
FDA Food and Drug Administration of an antibiotic required to kill 99.99% of the initial bacterial
FLUTD Feline Lower Urinary Tract Disease population after 24 h. The calculation is made in broth.

510 511
Glossary
MDR Multi-drug resistance MRCoNS Meticillin-resistant coagulase-negative staphylococci
MET Meticillin MRS Meticillin-resistant staphylococci
METZ / Metronid Metronidazole MRSA Meticillin-resistant Staphylococcus aureus
MIC Minimal Inhibitory Concentration: the lowest concentration of an MRSI Meticillin-resistant Staphylococcus intermedius
antibiotic that will completely (100%) inhibit the growth of a MRSP Meticillin-resistant Staphylococcus pseudintermedius
microorganism. It is measured in µg/ml and is generally
MRT Mean Residence Time: the average amount of time that each of the
determined in a liquid (stock solution) environment by subsequent
antibiotic molecules persist in the organism. This average
dilutions. MIC values generally follow a geometric evolution:
persistence is a statistical approach (based on probabilities).
0.125 - 0.25 - 0.5 - 1.0 - 2.0 - 4.0 - 0.8 - 16 µg/ml etc.
It is usually expressed in hours.
For a single antibiotic, the collection of MICs for different bacterial
strains of the same species provides a statistical estimate of the MSSP Meticillin-susceptible Staphylococcus pseudintermedius
concentration that inhibits 50% (MIC50) and 90% (MIC90) of bacterial NA Nalidixic acid
isolates. MIC can also be calculated on agar dilution plates. NCT Non-randomised controlled clinical trials
The method is simple but requires prior calibration. For a
NEO Neomycin
bactericidal antibiotic, the MIC is very close to the MBC.
NIT Nitrofurantoin
MIC50 or MIC90 Lowest concentration of antibiotics that inhibits at least half (MIC50)
Appendices

Appendices
or 90% of the tested isolates. NOV Novobiocin
MLST Multi Locus Sequence Typing NSAID Nonsteroidal anti-inflammatory drug
modal MIC The most common MIC for the pathogens tested. ORB / Orbi Orbifloxacin
MPC Mutant Prevention Concentration: this corresponds to a higher OTC Oxytetracycline
concentration than the MIC90. The MPC inhibits the so-called low OXA Oxacillin
(or first) level resistance, and is defined as the lowest concentration P. aeruginosa Pseudomas aeruginosa
of an antibiotic that will inhibit the growth (in vitro) of a colony of
resistant mutant strains. PAE Post-Antibiotic Effect: persistent suppression of bacterial growth
after exposure even though antibiotic concentrations have
Wild-type dropped below the MIC. It usually lasts 1-4 hours for most
population C B A
antibiotics. It has mainly been assessed for macrolides and
Susceptible bacteria fluoroquinolones.
Resistant mutant
pAmpC Plasmidic AmpC ß-lactamases
C max PEN Penicillins
Concentration (mg/L)

Peni G Benzylpenicillin or penicillin G


MPC
Mutant PK/PD Pharmacokinetics/pharmacodynamics of a drug reflect the relation
selection between pharmacokinetic (PK) parameters such as the AUC and
window
MIC the Cmax, and pharmacodynamic (PD) parameters such as the MIC.
AUIC, IQ and t>MIC are so-called “dual” PK/PD indicators as they
Time (h) take into account both pharmacokinetic and pharmacodynamic
T max properties.
PO Per os (by mouth)
POLB Polymixin B

512 513
Glossary
Ppb Parts per billion (1 ppb = 1 ng/g = 1 µg/kg) distribution. Clearance is a parameter that is more difficult to
Ppm Parts per million (1 ppm = 1 µg/g = 1 mg/kg) understand, but it provides a better representation of the drug
elimination capacity. Elimination half-life (sometimes called t1/2ß)
Prado Pradofloxacin
corresponds to the half-life during the elimination phase.
PRI Pristinamycin The term absorption half-life is sometimes used to describe the
RCT Randomised controlled clinical trial absorption of drugs into the blood stream.
RIF Rifampin, rifampicin TET Tetracycline
S. aureus / SA Staphylococcus aureus TID Three times daily (tris in die)
S. epidermis Staphylococcus epidermis TIG Tigecycline
S. haemolyticus Staphylococcus haemolyticus Time-dependent Antibiotics for which the bactericidal (or bacteriostatic) activity is
S. intermedius Staphylococcus intermedius antibiotics unrelated to the concentration. To increase the efficacy, it is
necessary to prolong the exposure. The predictive criterion of
S. pseudinter - Staphylococcus pseudintermedius
efficacy is the t>MIC.
medius /
S. pseudint. / SP CFU/mL
SC / SQ Subcutaneous (log10) Time-dependent activity 2.5 Plasma concentration curves
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Appendices
SDR Single drug resistance 9 Control 2

SF Sulfonamide 0,032 mg/l 1.5 T>MIC


7 0.063 mg/l
SIG Staphylococcus intermedius group 0.125 mg/l 1

5 0.25 mg/l
SPC Summary of Product Characteristics: the document approved by the 0,5
1 mg/l
medicines agencies and authorities, describing the drug and the 0
3 Time (h) 0 20 40 60
use approved by the authorities, in particular regarding indications, 0 2 4 6 24
Time (h)
dosage regimen, warnings, precautions and contraindications.
Spira Spiramycin
TMP/SMX Trimethoprim-sulfamethoxazole
SSI Surgical Site Infection
TMPS Trimethoprim sulfonamide
STR Streptomycin
TMS Trimethoprim+sulfonamide, trimethoprim-sulfamethoxazole
t>MIC The time the plasma concentration of an antibiotic remains above
Tylo Tylosin
the MIC. It is expressed in time (hours) or in a percentage of the
interval between two administrations (generally 12 or 24 hours in UTI Urinary Tract Infection
animals). For time-dependent antibiotics, the percentage should be VAN Vancomycin
as high as possible, i.e. at least 70%. Vd Apparent volume of distribution: the theoretical volume that
t1/2 Half-life: the time it takes for the plasma concentration to be would be necessary to contain the total amount of an administered
halved. During the so-called elimination phase, this value is drug at the same concentration that is observed in plasma in case
independent of the concentration; the same amount of time is of a uniform distribution. It is generally expressed in L/kg. Colistin
required for the plasma concentration to go from 2 to 1 µg/ml and aminoglycosides are examples of antibiotics that do not
as from 0.5 to 0.25 µg/ml. This criterion, which is easy to distribute well throughout the organism; colistin does not pass
understand as an elimination rate constant or persistence of the phospholipid membranes and aminoglycosides have an
antibiotic in the body, should be interpreted with care. Indeed, the extracellular distribution. Their distribution volumes are relatively
half-life does not only depend on the elimination but also on low, between 0.6 and 1 L/kg.

514 515
Glossary
By definition, distribution volumes cannot be lower than the plasma
volume in the organism (around 0.2 L/kg). Antibiotics that readily
pass through phospholipid membranes and even accumulate
inside cells will have distribution volumes exceeding 1L/kg,
generally 2 to 4 L/kg. However, distribution volumes do not predict
antibiotic tissue concentrations.
VRE Vancomycin-resistant Enterococcus spp.
WHO World Health Organisation
WOAH/OIE World Organisation for Animal Health
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516 517
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