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VOL 21(12M) • DECEMBER 1 9 9 9

Third International Veterinary Symposium on Fluoroquinolones

PROCEEDINGS
SUPPLEMENT TO COMPENDIUM ON CONTINUING EDUCATION FOR THE PRACTICING VETERINARIAN ®

PHARMACOLOGY/
MICROBIOLOGY

DERMATOLOGY

RESPIRATORY TRACT
INFECTIONS

URINARY TRACT
INFECTIONS

PERIODONTAL
DISEASE

SMALL MAMMALS/
EXOTICS

SEVILLE, SPAIN
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VOL 21(12M) • DECEMBER 1 9 9 9

Third International Veterinary Symposium on Fluoroquinolones

PROCEEDINGS
SUPPLEMENT TO COMPENDIUM ON CONTINUING EDUCATION FOR THE PRACTICING VETERINARIAN ®

Seville, Spain
March 11–12, 1999
Guest Editor
Richard B. Ford, DVM, MS

This symposium was held in cooperation with:

The Spanish Association for Veterinarians
Specializing in Small Animals
Spain
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Bayer Corporation
9009 West 67th Street
Shawnee Mission, Kansas 66202
U.S.A.

Library of Congress No. 99-75828

ISBN 1-884254-48-9

Copyright © 1999, Bayer Corporation and Bayer AG Leverkusen

All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or

transmitted in any form or by any electronic or mechanical means, by photocopying
or recording, or otherwise without the prior permission of the copyright owner.

The views expressed in this publication represent those of the authors and do not
necessarily reflect those of Bayer or Bayer subsidiaries.

This manual is intended primarily as an overview of a scientific topic, as dosages are

cited for several pharmacologic agents that may not be the same as those stated on
their data sheets in a given country.

In addition, dosages are included for pharmacologic products that may not be
licensed for veterinary use in a given country.

Veterinary practitioners/surgeons should consult their local data sheet or equivalent

for licensing/prescribing conditions in their particular country.

Queries relating to the enclosed information should be addressed to the Animal

Health Business Group of Bayer in each individual country.

Printed in U.S.A.
Designed and published by Veterinary Learning Systems, a division of MediMedia
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Bayer AG
Business Group Animal Health
51368 Leverkusen
Germany

Library of Congress No. 99-75828

ISBN 1-884254-48-9

Copyright © 1999, Bayer Corporation and Bayer AG Leverkusen

All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or

transmitted in any form or by any electronic or mechanical means, by photocopying
or recording, or otherwise without the prior permission of the copyright owner.

The views expressed in this publication represent those of the authors and do not
necessarily reflect those of Bayer or Bayer subsidiaries.

This manual is intended primarily as an overview of a scientific topic, as dosages are

cited for several pharmacologic agents that may not be the same as those stated on
their data sheets in a given country.

In addition, dosages are included for pharmacologic products that may not be
licensed for veterinary use in a given country.

Veterinary practitioners/surgeons should consult their local data sheet or equivalent

for licensing/prescribing conditions in their particular country.

Queries relating to the enclosed information should be addressed to the Animal

Health Business Group of Bayer in each individual country.

Printed in U.S.A.
Designed and published by Veterinary Learning Systems, a division of MediMedia
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Contents

4 Preface 57 Use of Systemic Antimicrobials in

Canine Bacterial Otitis
5 Introduction: A Decade of Fluoroquinolone John M. MacDonald, MEd, DVM
Therapy in Small Animal Medicine

6 Foreword RESPIRATORY TRACT INFECTIONS

60 Management of Bacterial Bronchitis and
PHARMACOLOGY- Pneumonia in Small Animals
Lesley G. King, MVB, MRCVS
MICROBIOLOGY
7 Overview of the Pharmacokinetic URINARY TRACT INFECTIONS
Properties of Fluoroquinolones in
Companion Animals 65 Therapy of Canine and Feline Urinary Tract
M. Kietzmann, Prof Dr med vet Infections with Enrofloxacin
David J. Polzin, DVM, PhD
12 Comparative Pharmacokinetics of
Enrofloxacin and Difloxacin as Well as 73 Diagnosis and Treatment of Canine Bacterial
Their Main Metabolites in Dogs Prostatitis
Ernst Heinen, Dr med vet Walter R. Threlfall, DVM, PhD,
Dennis J. Chew, DVM
19 Bactericidal and Inhibitory Activity of
Enrofloxacin and Other Fluoroquinolones
in Small Animal Pathogens PERIODONTAL DISEASE
F. Pirro, Dr med vet, M. Edingloh, Dr med vet,
N. Schmeer, Prof Dr med vet 88 Clinical Experience with an Enrofloxacin-
Metronidazole Combination in the
26 Antimicrobial Movement into Tissues: The Treatment of Periodontal Disease in Dogs
Impact of Antimicrobial Accumulation by and Cats
Phagocytes David Nielsen, DVM
Dawn Merton Boothe, DVM, PhD, Albert Boeckh, DVM,
Scott Wilkie, BS, Harry W. Boothe, DVM, MS SMALL MAMMALS/EXOTICS
32 Serum and Tissue Concentrations of 95 Treatment of Bacterial Infectious Diseases in
Enrofloxacin in Dogs Pet Rabbits and Other Small Mammals
Dawn Merton Boothe, DVM, PhD, Albert Boeckh, DVM, Thomas Göbel, Dr med vet
Scott Wilkie, BS, Harry W. Boothe DVM, MS
107 Use of Enrofloxacin (Baytril®) in Psittacine
40 Time Course of Enrofloxacin and Its Active Birds
Metabolite in Peripheral Leukocytes of Dogs Keven Flammer, DVM
Albert Boeckh, DVM, Dawn Merton Boothe, DVM, PhD,
Scott Wilkie, BS 110 Pharmacokinetics of Enrofloxacin in Reptiles
Mark G. Papich, DVM, MS
DERMATOLOGY 115 Practical Antibiotic Selection in Avian
44 German Shepherd Dog Pyoderma: An Patients
Overview and Antimicrobial Management Don J. Harris, DVM, Vanessa Koehler, CRA
Peter J. Ihrke, VMD, Terese C. DeManuelle, DVM

50 Comparison of Enrofloxacin Skin

Concentrations in Normal Dogs and in Dogs
with Pyoderma
Terese C. DeManuelle, DVM, Peter J. Ihrke, VMD
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Preface
The evolution of Western medicine is a fascinating account of our successes and failures in attempting to understand and
treat disease. It is a history based largely on the ravages of epidemic infections in which millions of people died and entire
nations were threatened. It was and continues to be a story of discovery and of how one success, often emerging after years
of frustration and failure, served as the critical link to what we now regard as a major milestone in treating disease. From vac-
cines to insulin, scores of medical discoveries stand out today as milestones in the war against disease and premature death.
Yet one of the most historically significant medical discoveries was the production of an antibacterial compound that, unique-
ly, was capable of killing the agents of infection without harming the host. Today, armed with hundreds of such compounds,
antimicrobial therapy remains the cornerstone of treatment in the battle against infectious disease.
Yet, despite the incredible contributions antimicrobials have made to human and animal health, the history of antimicro-
bial therapy is relatively brief. In fact, the search for effective antimicrobial compounds did not even intensify until the begin-
ning of the 20th century. Results of initial studies were particularly discouraging, as most compounds were found to be equal-
ly toxic to microbes and patients.
The first substantial breakthrough in antimicrobial therapy came in 1932 and is credited to a German scientist, Gerhard
Domagk. While working in the “dye-stuff” industry in the Bayer laboratories, Domagk discovered that one of the dyes he
worked with, called prontosil red, destroyed hemolytic streptococcal infections in mice without (remarkably!) killing the mice.
Subsequent studies in children with so-called puerperal fever substantiated these antimicrobial properties and eventually
revealed that the antibacterial property of prontosil red was linked to a substance called sulfanilamide. Subsequent research
yielded a variety of analogues; eventually, a new class of drugs, the sulfonamides, emerged. The success of these compounds
in treating pneumonia, meningitis, and puerperal fever led to rapid manufacture and widespread use. Even though penicillin
had been discovered some years before, the sulfonamides were the very first antimicrobials to be used in clinical practice.
Today, as we are about to enter the 21st century, physicians and veterinarians have at their disposal an impressive spec-
trum of choices in antimicrobial drug therapy. Among them, the class of antimicrobials called the fluoroquinolones predomi-
nates as a milestone in the legacy of antimicrobial therapy. Ten years ago the first fluoroquinolone, enrofloxacin, was intro-
duced into veterinary medicine as Baytril® (Bayer). It is important to note that in veterinary medicine, Baytril® continues to be
acknowledged in a global marketplace as the leading antimicrobial in companion animal medicine.
The manuscripts published in these proceedings of the Third International Veterinary Symposium on Fluoroquinolones are
testimony to the fact that enrofloxacin has become the most thoroughly studied antimicrobial developed exclusively for use
in veterinary medicine. Of particular importance is the fact that, after 10 years, new information and clinical applications are
still being identified and new therapeutic opportunities are still being realized.
As chairperson of this Symposium, I would like to acknowledge each of the distinguished participating authors for the time
and effort they have put into advancing the body of knowledge of enrofloxacin. Just as with the two previous symposia on
fluoroquinolones, the information presented herein will have immediate and important application in the clinical setting.
Also, I wish to acknowledge the Bayer Corporation for its support of veterinary medicine and its unprecedented commit-
ment over the past 10 years to understanding the pharmacology and clinical applications of fluoroquinolones and, particu-
larly, Baytril®. Information and discovery are very much a part of the Baytril® experience … one that is expected to persist well
into the 21st century.

Richard B. Ford, DVM, MS

Chairman

4 Third International Veterinary Symposium on Fluoroquinolones Proceedings

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Introduction: A Decade of Fluoroquinolone

Therapy in Small Animal Medicine
Veterinary medicine, traditionally focused on livestock, has changed enormously in the past 20 years. Radical alterations in
the structure of society, such as increasing urbanization, social isolation, and lack of communication, have led people to seek
alternatives to human partnership in their social environment. Within the last few years a phenomenon called the “human-
animal bond“ has developed. Dogs and cats are no longer valued solely for their practical benefits, such as hunting, guard-
ing, herding, or, in the case of cats, rodent control. Dogs and cats have become social partners, especially for single persons
and the elderly, surrogates for children, and fully established family members.
It is obvious that owners expect the same level of care for their pets as for any human member of the family. This is one
reason for the dramatic development of small animal medicine in the last two decades. The diagnostic and therapeutic pos-
sibilities of modern veterinary medicine now closely shadow those of human medicine.
This also applies to options in drug therapy. Whereas once veterinary practitioners had to use products registered for
humans or livestock to treat small animals, an increasingly sophisticated and demanding companion animal sector has led to
the development of drugs specifically for the treatment of dogs and cats. Today, a large armamentarium of effective thera-
peutic agents is tailored to the needs of the small animal practitioner.
An important example involves the quinolones, the most recently developed class of antiinfectives for human and veteri-
nary medicine. Accidentally discovered as a byproduct of antimalarial research by George Lesher in 1962, this new class of
active anti-microbial developed quickly. The first agents for therapeutic use in humans, such as nalidixic and oxolinic acids,
however, had serious disadvantages, such as poor antimicrobial activity, inferior pharmacokinetic properties, and numerous
side effects. The introduction of a fluorine atom at position 6 of the core structure, common to all quinolones, led to a marked
increase in antibacterial efficacy and to a substantial improvement in the pharmacokinetics of these drugs. Of this group, nor-
floxacin, introduced to human medicine in 1983, was the first fluorinated quinolone.
In 1980 Bayer researchers Grohe and Peterson synthesized a new compound that became the first quinolone for veterinary
use. Ten years ago this product was first launched in The Netherlands, Sweden, and New Zealand under the brand name of
Baytril® to treat infectious bacterial disease in dogs and cats.
Today this fluoroquinolone is firmly established in the antiinfective segment of small animal medicine. It is the standard
fluoroquinolone worldwide and the leading antiinfective in many countries. The vast amount of scientific information and clin-
ical experience relating to this product has been recorded in more than 1,000 international publications, and that number is
constantly increasing.
Few antimicrobials have had the same impact on small animal medicine as Baytril. Many of the facts that we know about
fluoroquinolones today are based on experimental studies performed with this molecule. Although Baytril is the best docu-
mented quinolone in small animal medicine worldwide, new questions must be answered and many possibilities wait to be
uncovered. We have learned much already, but we wish to know more.
In light of this quest for knowledge, during the past 10 years Bayer has undertaken a commitment to continuing educa-
tion of the veterinary profession whereby the latest information on quinolones is collated and presented every few years at
our fluoroquinolone symposia to a gathering of internationally renowned scientists and practicing veterinarians who are
authorities in their fields.
Seville, a town so rich in history by any standards and influenced by many cultures, was the venue for our Third Interna-
tional Veterinary Symposium on Fluoroquinolones. During the 2 days of the symposium, speakers of international reputation
shared their knowledge with a truly international gathering of veterinary practitioners and scientists from around the world,
with a valuable exchange of knowledge and experiences.
Bayer is especially grateful to our symposium chairman and guest editor Richard Ford for his valuable input and for the
review of the papers presented at this symposium.
I would also like to thank all the speakers, who have given so much time and effort to sum up the current state of knowl-
edge in their fields and who readily share that knowledge with the veterinary community.
Finally, we are especially grateful to the AVEPA, the Spanish Association for Veterinarians Specializing in Small Animals, and
in particular to Dr. Francisco Florit and Dr. Javier Vilamore, for their invaluable help in organizing the conference.

Gert R. Daube, Dr med vet

Bayer AG Germany

Supplement to Compendium on Continuing Education for the Practicing Veterinarian, Vol. 21, No. 12(M), 1999 5
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Foreword
In the 10 years since the introduction of Baytril®, knowledge about the role of enrofloxacin in treating infectious diseases
has continued to be accumulated at a rapid speed. Bayer has sponsored two other international symposia to help disseminate
this information to the practicing veterinarian. Providing this forum for leading scientists from around the world to share their
knowledge is only one of the ways Bayer expresses its commitment to the veterinary profession.
The papers presented at the Third International Veterinary Symposium on Fluoroquinolones serve to illustrate the sustain-
ing role of enrofloxacin, the first fluoroquinolone approved for use in veterinary medicine, in clinical practice. Of particular
interest is the fact that several of the distinguished faculty address new studies on the exceptional pharmacology and micro-
biology of enrofloxacin compared to other fluoroquinolones available to veterinarians today. These papers provide new insight
into the antimicrobial activity of enrofloxacin and serve to bridge the gap between the research laboratory and clinical prac-
tice. In addition, this section of the symposium includes previously unpublished information on not only the extracellular dis-
tribution of enrofloxacin in companion animal species but also discusses the intracellular distribution of enrofloxacin in phago-
cytes and peripheral leukocytes in dogs.
Five additional sections of the symposium are dedicated to new clinical applications and indications pertinent to the use of
enrofloxacin. Specific emphasis has been placed on such important disorders as German Shepherd pyoderma and bacterial
otitis externa. Also included are presentations on the role of enrofloxacin in treating dogs and cats diagnosed with lower res-
piratory infection. Furthermore, various specialists discuss the role of enrofloxacin in treating lower urinary tract infections and
bacterial prostatitis. One paper described experience using enrofloxacin in combination with metronidazole in the manage-
ment of chronic periodontal disease in dogs and cats. The concluding section of the proceedings uniquely centers around clin-
ical applications of enrofloxacin in treating a variety of infections in small mammals, including rabbits, and birds. Never previ-
ously addressed, the symposium included one presentation on the pharmacokinetics of enrofloxacin in a wide variety of
reptiles, also presented here.
Clearly, the papers presented at this conference, the Third International Veterinary Symposium on Fluoroquinolones, rep-
resent the unique spectrum of therapeutic applications of enrofloxacin in veterinary medicine as well as the fact that new indi-
cations are still being discovered 10 years following its introduction into the marketplace.
It is a great honor for the Spanish Association for Veterinarians Specializing in Small Animals (AVEPA) to participate in the
Third International Veterinary Symposium on Fluoroquinolones. We believe that the choice of Spain, Andalusia, and particu-
larly Seville with its unquestionable charm contributed to make this international event of great scientific content one to be
remembered with great satisfaction for many years to come.
A large number of the veterinary profession’s elite gathered at this congress to study and discuss the most recent advances
in the control and treatment of infectious disease and the role of fluoroquinolones. As was shared at this meeting, new infor-
mation and new therapeutic applications for enrofloxacin are still being discovered.
On behalf of the AVEPA and all Spanish veterinarians, I would like to acknowledge Bayer Corporation for its ongoing com-
mitment to the veterinary profession.

Francisco Florit, DVM

President
AVEPA (Asociación de Veterinarios Españoles Especialistas en Pequeños Animales)

6 Third International Veterinary Symposium on Fluoroquinolones Proceedings