IMPACT Guideline

Reducing bacterial resistance with IMPACT –
Interhospital Multi-disciplinary Programme on Antimicrobial

ChemoTherapy
This guideline is available for download at:
HKU Centre of Infection

http://www.hku.hk/hkucoi/impact.pdf
DH Centre for Health Protection

http://www.chp.gov.hk/files/pdf/reducing_bacterial_resistance_with_impact.pdf
HA intranet
http://ha.home/ho/ps/impact.pdf
IMPACT Third Edition (Version 3.0) 1

Editors: PL Ho and SSY Wong
Third Edition 2005

Version 3.0
Second edition: 2001 (ver 2.0), 2002 (ver 2.1), 2003 (ver 2.2)
First edition: 1999
All rights reserved. No part of this publication may be reproduced,
stored in a retrieved system, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, and recording or
otherwise, without the prior approval from IMPACT
We seek to improve the quality of this document. If you have

comments or suggestion on this draft, please email to
plho@hkusua.hku.hk or hkumicro@hkucc.hku.hk
NOTICE
This publication contains information relating to
general principles of medical care, which should not be
construed as specific instructions for individual patients.
Manufacturers' product information and package inserts
should be reviewed for the latest information,
including contraindications, dosages and precautions. The editors, the
working group and publisher are not responsible for errors or
omissions or for any consequences from the application of the
information in this document and make no warranty, express or
implied, with respect to the currency, accuracy, or completeness of the
contents of the publication. Application of this information in a
particular situation remains the professional responsibility of the
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may not be available in their instutues.

IMPACT Working Group
Co-chairpersons
Dr. Raymond Wai Hung, Head, Infection Control Branch,
YUNG Centre for Health Protection,
Department of Health
Dr. Dominic Ngai Chong, Consultant Microbiologist,

TSANG Department of Clinical Pathology
Queen Elizabeth Hospital
Members (alphabetical
order)
Dr. S Anandaciva Consultant

Department of Anaesthesiology and
Intensive Care Unit
Tuen Mun Hospital
Dr. Kin Sang, CHAN Chief of Service

Department of Pulmonary Medicine
Haven of Hope Hospital
Dr. Wai Ming, CHAN Consultant

Intensive Care Unit
Queen Mary Hospital
Dr. Sik To, LAI Consultant

Department of Medicine
Princess Margaret Hospital
Dr. Wai Man, LAI Chief of Service

Department of Microbiology
Prince of Wales Hospital
Dr. Patrick CK, LI Chief of Service

Dr. Wei Kwang, LUK Senior Medical Officer

Department of Clinical Pathology
Tseung Kwan O Hospital

Dr. Tak Keung, NG Consultant Microbiologist
Princess Margaret Hospital
Dr. Tak Lun, QUE Consultant Microbiologist

Tuen Mun Hospital
Dr. Loletta KY, SO Senior Medical Officer

Pamela Youde Nethersole Eastern
Hospital
Dr. Wing Kin, TO Senior Medical Officer

Yan Chai Hospital
Dr. Kwan Keung, WONG Chief of Service

North District Hospital
Dr. Sai Hung, YEUNG Consultant

Department of Orthopaedic Surgery
Hospital
Dr. Wai Chun, YIP Chief of Service

Department of Surgery
Kwong Wah Hospital
Mr. Pak Wai, LEE Chief Pharmacist

Hospital Authority Head Office

Academic advisors
Professor Robert MT, CHAN Professor of Infectious Diseases

University of British Columbia
Vancouver, Canada
Dr. Pak Leung, HO Associate Professor and Honorary

Consultant
Division of Infectious Diseases,
Department of Microbiology &
Centre of Infection
The University of Hong Kong
Professor Margaret IP Professor

Department of Microbiology
Chinese University of Hong Kong
Professor Allan R. RONALD Distinguished Professor Emeritus

(Internal Medicine,
Medical Microbiology and
Community Health Sciences)
University of Manitoba
Canada
Professor Kenneth WT, TSANG Professor and Honorary Consultant

Queen Mary Hospital
Professor Kwok Yung, YUEN Chair Professor in Infectious Diseases

Division of Infectious Diseases,
Department of Microbiology &
Centre of Infection
The University of Hong Kong

Secretaries
Dr. Cindy WS, TSE Associate Consultant
Kwong Wah Hospital
Dr. Alan KL, WU Medical Officer

Hospital
Dr. Tak Chiu, WU Associate Consultant


Contents
List of tables ......................................................................................9
Foreword .........................................................................................10
Preface.............................................................................................11
Part I: Antibiotic resistance- local scenario ..................................12
Methicillin-resistant Staphylococcus aureus......................................16

Vancomycin-resistant enterococci .....................................................17
ESBL-producing Enterobacteriaceae .................................................17
Enterobacter spp. .............................................................................19
Part II: Antimicrobial stewardship programme .............................21
Antimicrobial stewardship program: summary .................................22

Classification of therapy...................................................................34
Part III: Guidelines for selected antimicrobials use ......................37
Vancomycin .....................................................................................38
Quinupristin/dalfopristin and linezolid ............................................43
Ceftazidime......................................................................................45
Imipienem/meropenem/ertapenem ..................................................48
Once daily aminoglycosides..............................................................50
Summary of selected antifungal agents ............................................54
Part IV: Recommendation for the empirical therapy of common

infections .......................................................................................59
Musculoskeletal infections ...............................................................60

Skin and soft tissue infections .........................................................61
Central nervous system infections....................................................62
Intra-abdominal and GI system infections ........................................63
Cardiovascular infections.................................................................64
Gynaecological infections .................................................................65
Head and neck infections .................................................................65
Urinary tract infections ....................................................................65
Respiratory tract infections ..............................................................66
Guidelines on the use and choice of antibiotics in severe acute
pancreatitis .....................................................................................71
Management of community-acquired pneumonia .............................74
General considerations and principles..............................................74

Part V: Guidelines for known pathogen therapy ...........................81
Part VI: Guidelines for surgical prophylaxis..................................88
Antibiotic prophylaxis in clean operations ........................................90

Antibiotic prophylaxis in clean-contaminated operations ..................92
Antibiotic prophylaxis in contaminated-infected operations ..............94
Part VII: Cost and recommended dosage of commonly-used

antimicrobial agents ......................................................................95
Preparation and recommended dosing regimens for antibiotics .........96

Cost comparison of selected IV antibiotics ......................................100
Cost comparison of systemic antifungal agents...............................102
Dosage of antimicrobial agents for CNS infections ..........................103
Intra-peritoneal antibiotic dosing recommendations for patients with
CAPD peritonitis ............................................................................104
Reference List ................................................................................105

Abbreviations.................................................................................123

List of tables
Table 1. Top ten isolates from clinical specimens in 2004 (data from a
regional hospital in Hong Kong). .......................................... 14
Table 2. Intrinsic and associated resistance to antimicrobial agents
among five nosocomial pathogens. ....................................... 15
Table 3. Methods to implement antimicrobial control......................... 28
Table 4. Potential barriers to reaching the strategic goals .................. 29
Table 5. Summary of published data on antimicrobial strategies as an
intervention to reduce ESBL resistance................................ 33
Table 6. Strategies for optimization of antimicrobial therapy .............. 36
Table 7. Dosage table for vancomycin................................................ 41
Table 8. Calculation of vancomycin dose for morbidly obese patient... 42
Table 9. Comparison of linezolid and quinupristin/dalfopristin.......... 44
Table 10. Hartford Hospital once-daily aminoglycoside normogram for
gentamicin and tobramycin ................................................. 53
Table 11. General patterns of antifungal susceptibility ...................... 54
Table 12. Comparison of susceptibility of selected fungi to the azoles 55
Table 13. Mechanisms of antifungal action........................................ 56
Table 14. Comparison of selected pharmacokinetic parameters for the
azoles and caspofungin ...................................................... 57
Table 15. A suggested scheme for systemic antifungal agents ............ 58
Table 16. Criteria for severity assessment of acute pancreatitis ......... 72
Table 17. Prophylactic use of antibiotic in acute pancreatitis ............. 73
Table 18. Comparative activities of commonly used beta-lactams
against Streptococcus pneumoniae with different levels of
penicillin susceptibility....................................................... 80

Foreword
Antibiotics are one of the essential armaments for management of infections.
Antimicrobial resistance results in increased morbidity, mortality, and costs of
health care. It is becoming a global problem. Prevention of the emergence of
resistance and the spread of resistant microorganisms will reduce these adverse
effects and their attendant costs. Promoting appropriate use of antibiotic has
shown to be an effective means to control antimicrobial resistance.
In Hong Kong, our long-term battle against antibiotic resistance continues and
antimicrobial guideline is an essential tool to promote rational use of
antimicrobial agents with better application of existing knowledge and adherence
to good practice.
The IMPACT was developed in 1999 as a first step towards better control of the
growing problem of antimicrobial resistance in Hong Kong. Developed with a
multidisciplinary approach with inputs from different specialties and institutions,
the IMPACT took into account the local data on prevalence of different pathogens
and antimicrobial resistance patterns.
Now into its third edition, the IMPACT has incorporated constructive comments
from clinicians and other colleagues as part of an on-going effort to keep abreast
of new antibiotics, changing resistance patterns and literature. This specifically
developed guideline for practitioners in Hong Kong provides evidence-based
principles focused on situations in which antimicrobial therapy could be
curtailed without compromising patient care.
The third edition of the IMPACT is a timely update to coincide with the launching
of the Antibiotic Stewardship Programme by the Hospital Authority which
includes optimal selection, dose and duration of treatment, as well as control of
antibiotic use. The IMPACT constitutes an essential element along with other key
elements of education, user-feedback, regular updates, clinical audits and
process evaluation in this comprehensive Programme.
I thank the many individuals and organizations who have contributed to the
compilation of IMPACT and look forward to your continued support and
partnership in our Antibiotic Stewardship Programme.
Dr Cheung Wai-lun
Director
Professional Services and Operations
Hospital Authority

Preface
The “IMPACT” programme is a collaborative effort by recognized

authorities in the areas of clinical microbiology and infection,
infectious diseases, public health medicine, hospital epidemiology,
intensive care medicine, respirology, surgery, orthopaedics and
traumatology, and clinical pharmacology. The IMPACT working group
recognizes the challenges from drug-resistant organisms and believes
that the adverse impact of antimicrobial resistance could be reduced
through a better and more judicial use of the existing agents. The
document is intended to be of interest and value to colleagues who
practise in institutional settings and prescribe or evaluate
antimicrobial agents.
This new edition updates and revises all the information in the
previous edition. The document is now organized into eight parts. Part
1 and II covers the background information. Part III provides
guidelines on the use of six classes of antibiotics. They are discussed
separately because they represent new agents (linezolid, quinupristin-
dalfopristin), agents in which usage has a strong link to development
of multidrug-resistant organisms (glycopeptides, ceftazidime, and
carbapenems) or that the dosing and monitoring are complicated
(aminoglycosides). Several new sections have been added:
antimicrobial stewardship programme, severe acute pancreatitis,
antifungal agents, and antibiotic dosing for CAPD peritonitis. The font
size and the print-out size have been increased to enhance readability.
A full list of tables and a quick reference are added to facilitate the use
of this book.
The editors are grateful to the contributions by our experts in the

working group. The secretaries are skillful and meticulous in their
attention to the compilation of the document. On behalf of the working
group, we thank the Infection Control Branch of the Centre for Health
Protection for providing administrative support, the Chief Pharmacist
Office in the Hospital Authority for the generous support in printing
the hard copies and all colleagues who have provided us with their
valuable opinions in the preparation of this document.
PL Ho
SSY Wong
November 2005

Part I: Antibiotic resistance – local scenario
Part I: Antibiotic resistance- local scenario

Background: the problem of antimicrobial resistance in

Hong Kong
1. The emergence of resistance has threatened the successful
treatment of patient with infections (1-5).
2. Antimicrobial resistance increases drug costs, length of stay and

adversely affects patient’s outcome (6).
3. Resistance to all classes of antibiotics has developed to various

extents among the common and important nosocomial pathogens
(Tables 1 and 2).

Table 1. Top ten isolates from clinical specimens in 2004 (data from a regional hospital in Hong
Kong).
Blood Respiratory specimens Urine
n=1801 n=366 n=6303 n=1669 n=9201 n=232
Organism Non- ICU rank Organism Non- ICU rank Organism Non- ICU rank
ICU/HDU (%) ICU/HDU (%) ICU/HDU (%)
rank (%) rank (%) rank (%)
E. coli 1 (24%) 2 (10%) P. aeruginosa 1 (12%) 3 (8%) E. coli 1 (40%) 2 (21%)
Coagulase-negative 2 (15%) 1 (38%) S. aureus 2 (8%) 1 (9%) Enterococci species 2 (11%) 3 (13%)
staphylococci
K. pneumoniae 3 (9%) 5 (7%) H. influenzae 3 (6%) - Klebsiella species 3 (11%) 4 (11%)
Bacillus species 4 (8%) 3 (9%) Klebsiella 4 (4%) 2 (9%) Candida species 4 (8%) 1 (32%)
species
S. aureus 5 (7%) 6 (5%) S. pneumoniae 5 (4%) - Proteus species 5 (5%) 6 (3%)
Enterococcus species 6 (3%) 4 (9%) A. baumannii 6 (4%) 6 (4%) P. aeruginosa 6 (5%) 5 (7%)
A. baumannii 7 (2%) 9 (1%) M. catarrhalis 7 (3%) - Coagulase negative 7 (3%) 7 (2%)

staphylococci
P. aeruginosa 8 (2%) 7 (2%) E. coli 8 (3%) 7 (4%) S. aureus 8 (2%) 8 (2%)
B. fragilis group 9 (2%) 10 (1%) Enterobacter 9 (2%) 5 (5%) S. agalactiae 9 (2%) -

species (Lancefield gp B)
P. mirabilis 10 (2%) - S. maltophilia 10 (2%) 4 (5%) M. marganii 10 (2%) -
(Percentage omitted if number of isolates is less than 30)

Table 2. Intrinsic and associated resistance to antimicrobial

agents among five nosocomial pathogens.
INTRINSIC ASSOCIATED
BACTERIA RESISTANCE RESISTANCE
MRSA All beta-lactams, beta- Common: erythromycin,
lactam/beta-lactamase clindamycin,
inhibitor combinations aminoglycosides,
cotrimoxazole,
fluoroquinolones
VRE All cephalosporins, Common: ampicillin,
cotrimoxazole, imipenem, meropenem,
clindamycin, vancomycin, high level
aminoglycosides aminoglycoside
resistance
ESBL-producing All cephalosporins Common:
Enterobacteriaceae including fourth fluoroquinolones,
(CTX-M, SHV-, TEM- generation gentamicin,
derived) cephalosporin (7), all cotrimoxazole
penicillins, aztreonam
Derepressed AmpC-type First, second and third Common:
mutant among E. generation fluoroquinolones,
cloacae, C. freundii, S. cephalosporins, most gentamicin,
marcescens beta-lactam/beta- cotrimoxazole
lactamase inhibitor
combinations, cefoxitin
A. baumannii Ampicillin, first and Third generation
second generation cephalosporins,
cephalosporins fluoroquinolones,
aminoglycosides, (r
imipenem, meropenem)
(8)

Methicillin-resistant Staphylococcus aureus

On the basis of the patient history and epidemiological analysis,
Methicillin-Resistant Staphylococcus aureus (MRSA) may be
categorized into healthcare-associated or community-associated.
Healthcare-associated MRSA (HA-MRSA)
This type of MRSA is endemic in the local healthcare environment

including hospitals, extended care facilities and old age homes since
the mid-1980s (3;4;9). The HA-MRSA tends to be isolated in
patients who are hospitalized for more than 48 hours. Since MRSA
carriage may persist for many months after a previous acquisition,
HA-MRSA also include those isolates that are found at admission
(or within 48 hours) from patients who possess risk factors for their
carriage including hospitalization in the previous 1 year, recent
surgery, old age home residence, renal dialysis and exposure to
invasive devices and employment in a healthcare institute (10;11).
In Hong Kong, 30-50% of all hospital S. aureus isolates are

currently resistant to methicillin. The proportion of MRSA increased
to 70-80% among isolates from intensive care units (ICU). In 1999,
a study involving ICUs in 11 public hospitals showed 12% of the
patients were MRSA carriers at ICU admission and that new
acquisition of MRSA occurred in about 12% of the patients who
were non-carriers initially (12).
Most HA-MRSA also encode a battery of other resistance genes, they

are thus multiresistant to drugs in other antibiotic classes including
aminoglycosides, macrolides, fluoroquinolones and clindamycin
(3;12).
Community-associated MRSA (CA-MRSA)
1. Patients infected with CA-MRSA do not have the usual risk factors
associated with HA-MRSA. In overseas countries, CA-MRSA were
found to be more common among certain populations: children with
chronic skin condition, prisoners, military personnel, aboriginals,
injection drug users, the homeless and contact sports athletes (13-
16); but such associations have not been observed among the CA-
MRSA cases in Hong Kong.

2. This organism often remains susceptible to antibiotic classes other

than beta-lactams, including clindamycin, aminoglycosides,
tetracyclines and fluoroquinolones.
3. The genotypes of CA-MRSA are different from the local nosocomial

strains. Most CA-MRSA strains in Hong Kong represent members in
clonal cluster 30, similar to the situation in the Southwest Pacific
region (17).
4. CA-MRSA possesses novel types of methicillin-resistance cassette

elements: type SCCmec IV or V, which are rare among the HA-
MRSA strains.
5. CA-MRSA is more likely to encode the virulence factor, Panton-

Valentine leukocidin (PVL) toxin, which is associated with skin/soft
tissue infections and severe necrotizing pneumonia (18).
Vancomycin-resistant enterococci
VRE here refers to E. faecium and E. faecalis with resistance to
glycopeptides (vancomycin MIC t8 Pg/mL or teicoplanin MIC t16
Pg/mL). The incidence of VRE in Hong Kong is low at present. The first
isolate of VRE (E. faecium) in Hong Kong was imported in 1997. In the
subsequent 3 years, a few sporadic cases were identified in five
hospitals including a small cluster recently in TMH. By the end of
March 2001, about 10 cases of VRE have been detected, including
both vancomycin-resistant E. faecium (vanA and vanB) and E. faecalis
(vanA) (19). In a multicentre surveillance of 1600 consecutive patients
hospitalized in >10 ICUs in 1999, the prevalence was found to be
<0.1%.
ESBL-producing Enterobacteriaceae
1. Extended-Spectrum Beta-Lactamases (ESBLs) are any bacterial
enzymes that are capable of inactivation of third generation
cephalosporins. The term is most commonly used to refer to a
group of bacterial enzymes that are derived from the classical
beta-lactamases TEM-1, TEM-2 and SHV-1. In recent years, the
“CTX-M” type of ESBL is also emerging in several Asian countries
including China and Hong Kong SAR (20-22).

2. ESBL may lead to therapeutic failures despite apparent

susceptiblity to some third generation cephalosporins in
conventional antibiotic sensitivity testing methods. The ESBLs
confer variable levels of resistance to cefotaxime, ceftazidime,
other broad-spectrum cephalosporins, and to monobactams such
as aztreonam, but had no detectable activity against the
carbapenems (such as imipenem, ertapenem and meropenem).
3. If antibiotic therapy is indicated (colonization do not need any

treatment other than infection control), serious infections by
ESBL-producers should be regarded as clinically resistant to all
the cephalosporins (including cefepime).
4. The ESBLs are usually encoded on genes in plasmids and

because of the ready transmissibility of the responsible plasmids,
dissemination of the resistance genes to other micro-organisms
occur readily. Since genes encoding resistance to multiple
antibiotics are often present in the same plasmid, co-transfer of
multiple resistance to non-beta-lactam drugs, such as
aminoglycosides, cotrimoxazole, chloramphenicol, and
tetracycline is common.
5. At present, the prevalence of ESBLs among Enterobacteriaceae

isolated in many tertiary hospitals around the world is over 10-
15%. In Hong Kong, a survey of four hospitals in 1997/98 (1200
non-duplicate clinical isolates) revealed rates of 6-23% for
Klebsiella pneumoniae and 9 -14% for E. coli. (23).
6. Numerous outbreaks due to ESBL-producing bacteria have been

reported. Known risk factors for colonization and/or infection
with organisms harbouring these enzymes include admission to
an intensive care unit, recent surgery, instrumentation,
prolonged hospital stay and antibiotic exposure, especially
exposure to third generation cephalosporins.
7. Incidence of ESBLs can decrease after changes in antibiotic

policy (mainly reducing the use of third generation
cephalosporins) and enforcement of barrier precautions (Table 5).
8. Most CTX-M, TEM- and SHV-derived ESBLs are susceptible to

inhibition by the beta-lactamase inhibitors and theoretically beta-
lactam/beta-lactamase inhibitor combinations should be active
against these isolates. It must be remembered that production of
ESBL doesn't preclude other mechanisms of resistance. In a
recent survey, it was found that 40-70% of the ESBL-producing

Enterobacteriaceae were resistant to amoxicillin-clavulanate,

ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin-
tazobactam and cefoperazone-sulbactam (20).
Enterobacter spp.
1. De-repression of AmpC beta-lactamase occurs most frequently
among Enterobacter spp. De-repressed mutants are resistant to
all the first, second and third generation cephalosporins.
2. AmpC-mediated resistance usually cannot be reversed by the

currently available beta-lactamase inhibitors. Hence, most de-
repressed mutants are also resistant to ampicillin-sulbactam,
amoxicillin-clavulanate, piperacillin-tazobactam, ticarcillin-
clavulanate, and cefoperazone-sulbactam.
3. It should be noted that resistance may develop in 20-40% of

serious Enterobacter infections during treatment with a second or
third generation cephalosporin (refer to Part V for treatment
recommendations).
4. In Hong Kong, a recent study found AmpC de-repression in 23%

of all Enterobacter spp. (21). It was also found that ESBL of the
CTX-M type may be emerging in some Enterobacter spp., such as
E. hormaechei. Therefore, laboratories should pay attention to
speciation of Enterobacter and be alert to the possibility of ESBL
production in this genus.
Multidrug-resistant Pseudomonas aeruginosa

1. Pseudomonas aeruginosa, a saprophyte widely distributed in nature
and moist habitats (e.g. sinks, respiratory equipment, antiseptic or
detergent solutions found in hospitals), is being increasingly
recognized as a nosocomial pathogen, especially among critically ill
or immunocompromised patients. Cross transmission or acquisition
among patients likely occurs through hands of healthcare workers,
or via contaminated fomites.
2. Under increasing antibiotic selection pressure, P. aeruginosa could

acquire increasing drug resistance, leading to emergence of multi-
drug-resistant phenotype (MRPA). By definition, MRPA isolates
exhibit beta-lactam multiresistance (piperacillin, piperacillin-

tazobactam, ceftazidime, cefepime, carbapenems), along with

resistance to aminoglycosides and quinolones (24-26); underlying
mechanisms include enhanced production and dissemination of
novel beta-lactamases, decreased outer membrane permeability,
and presence of drug efflux pumps (27;28).
3. During the past 10 years, there have been numerous reported

outbreaks of MRPA worldwide (29-33). According to the recent
global SENTRY surveillance conducted in 1997-1999, the rates of
MRPA (defined as being resistant to piperacillin, ceftazidime,
imipenem, and gentamicin) occurrence were as follows: Latin
America, 8.2%; Europe, 4.7%; United States, 1.2%; Asia Pacific,
1.6%; and Canada, 0.9% (34). More recent reports indicate that the
overall prevalence of MRPA continues to be on the rise, especially in
tertiary care institutions (35;36). The exact prevalence of MRPA in
Hong Kong is currently not known.
4. In patients suffering from chronic chest conditions (e.g. cystic

fibrosis), MRPA infection occurs after chronic airway colonization
(37); other patients appear to acquire the infection after
hospitalization. MRPA is predominantly isolated from respiratory
samples (35;38). Risk factors for nosocomial MRPA acquisition and
infection included: old age; severe underlying disease and / or being
bedridden (39); having maxillary sinusitis; high lung injury score
and / or need for prolonged mechanical ventilation (40;41); various
forms of instrumentation (e.g. urinary catheters and nasogastric
feeding tubes (39;39), long dwelling central venous catheters (41).
Prolonged use of antipseudomonal antibiotics such as beta-lactams,
carbapenems, and fluoroquinolones is also important risk factor
(38-41).
5. Treatment of MRPA infections is extremely difficult (42;43), because

MRPA can be resistant to all the currently available anti-
pseudomonal antibiotics, and may necessitate the use of unlicensed
and potentially toxic drugs such as colistin and polymyxin B, or
experimental combinations (44-46). Unfortunately, the new
antibiotics (such as glycylcyclines and ketolides) in the pipeline are
not active against MRPA. In view of this, MRPA infected or colonized
patients should be nursed in single rooms whenever feasible and
that all attending staff should practise hand hygiene for every
patient contact and other necessary standard and contact
precautions.

Part II: Antimicrobial stewardship programme

Antimicrobial stewardship program: summary

The present summary is based on an article in the Hong Kong
Medical Journal (47).
Antimicrobial drug resistance is now an important public health

threat because it endangers our ability to effectively treat infections.
A multi-faceted approach involving the continuous application of a
package of interventions should be implemented at regional and
international levels. In healthcare settings, the recommended
measures include infection prevention, effective diagnosis and early
treatment, using antimicrobials wisely and breaking the chain of
transmission (Centers for Disease Control and Prevention, 2003). In
the local settings, studies have found that there are rooms for
optimization of antimicrobial prescriptions in the hospitals.
Research conducted in the recent years further indicates that
improvement in the pattern of prescriptions is feasible and can be
implemented by means of antimicrobial stewardship programme
(ASP) in a safe, scientific and professional manner. As antibiotic-
resistant bacteria become more widespread, such initiatives will be
assuming increasingly important roles. Therefore, the Scientific
Committee on Infection Control in the Centre for Health Protection
recently come up with a document on “Optimizing antimicrobial
prescriptions in hospitals by antimicrobial stewardship programme
in Hong Kong: consensus statement”. The present text summarizes
the document under six broad questions:
1. What is the definition for optimal antimicrobial use?
Optimal antimicrobial use (prudent prescribing) has been defined as

“the cost-effective use of antimicrobials which maximizes their
clinical therapeutic effect, while minimizing both drug-related
toxicity and the development of antimicrobial resistance” (48;49).
This implies usage in the most appropriate way for the treatment or
prevention of human infectious diseases, having regard to the
diagnosis, evidence of clinical effectiveness, likely benefits, safety,
cost, and propensity for the emergence of resistance. Therefore,
optimal antibiotic use means both “less” use (i.e. less unnecessary
use), and “appropriate” use (i.e. not only the right antibiotic but also
the right dose, route and duration to effect a cure while minimizing
side effects and development of resistance according to the up-to-
date knowledge).

2. What is the rationale for optimizing antimicrobial use?
There are growing concerns about antimicrobial resistance. As

antimicrobial resistance increases, many previously time-honored,
first-line therapies are rapidly losing their efficacies and are
becoming obsolete (49). Antimicrobial resistance adds substantially
to our already rising healthcare costs, prolongs periods during
which individuals are infectious, increases morbidity, increases
length of hospital stay, and even mortality.
In developed countries, studies have found that 30-40% of

hospitalized patients were treated with antimicrobial agents. When
antimicrobial usage was studied, there are large variations in the
pattern of usage (50;51) and half of the usage could be classified as
suboptimal using recommended quality indicators (52;53). It is clear
that suboptimal use not only adversely affects patient outcome
(54;55), but also increases the risk of developing antimicrobial
resistance (52;53;56;57).
Currently, the issue of antimicrobial resistance is complicated

further by an insecure supply of new agents (58-60) and a
dwindling number of companies investing in antimicrobial agents
(61). Despite the dramatic rise of antimicrobial resistance in the
past five years, only two new classes of antibiotics were approved
since 2000: oxazolidinones (linezolid) and the cyclic lipopeptides
(daptomycin). In 2004, there are few novel antibacterial agents in
the pipeline. Thus, improving the use of existing antibiotics by all
clinicians is imperative.
3. What is antimicrobial stewardship programme? Who are the

advocacies? (Table 3)
The term antimicrobial stewardship is defined as the optimal

selection, dosage, and duration of antimicrobial treatment that
results in the best clinical outcome for the treatment or prevention
of infection, with minimal toxicity to the patient and minimal impact
on subsequent resistance (62). In practice, this involves prescribing
antimicrobial therapy only when it is beneficial to the patient,
targeting therapy to the desired pathogens and using the
appropriate drug, dose, and duration. Thus, ASP should not be
viewed simply as reduced use or a strategy for cost containment.
Instead, by minimizing exposure to drugs, performing dose
adjustments, reducing redundant therapy and targeting therapy to
the likely pathogens, such activities can be viewed as a strategy to

enhance patient safety.
ASP involves a multidisciplinary, programmatic, prospective,

interventional approach to optimizing the use of antimicrobial
agents. The multidisciplinary team typically includes clinical
microbiologists, infectious diseases specialists, infection control
practitioners, and clinical pharmacists. Having members from other
medical specialties, such as surgery and paediatrics, is also
recommended. Multiple approaches have been employed to enforce
hospital policies to limit or control antimicrobial use (Table 3).
Under the auspice of ASP, several behavioural methods have been
used successfully to effect changes, including problem-based
education, consensus guidelines, peer review, concurrent review,
data feedback, computer-based reminders, financial incentives, and
the use of opinion leaders (63;64).
Many professional societies and public health guardians including

the World Health Organization, Infectious Diseases Society of
America (IDSA), Alliance for the Prudent Use of Antibiotics (APUA),
Food and Drug Administration (FDA), Centers for Disease Control
and Prevention (CDC), National Institutes of Health (NIH) are
supportive of programmes that promote optimal antimicrobial use
(65;66). A few have even gone a step forward with action plans
(48;65-67).
4. Is there evidence that ASP is beneficial? How did people

document the benefits of the programme? Is there any evidence
that it leads to better and more optimal antibiotic use in the
hospital setting?
Most studies found this strategy effective in reducing the usage of

targeted antibiotics and in controlling antimicrobial expenditures. In
terms of its impact on antimicrobial resistance, programmatic
interventions in hospitals have yielded mixed results (68;69). The
reason for this is that the factors promoting resistance are complex
and multiple. It is clear that strong relationship exists between
certain antibiotic classes and multi-drug resistant pathogens such
as vancomycin with VRE; third generation cephalosporins with
ESBL; and fluoroquinolones with MRSA and MRPA. At an
institutional level, programmes designed to limit utilization of
agents that exert greater effect on the above were successful in
reducing the specific resistance rates.
Measurement and monitoring is an essential part of the programme.

After an initial implementation of a restricted formulary and
antimicrobial approval system as part of an antimicrobial control
programme, the team should meet regularly to review and update
the formulary, assess its effectiveness, provide and coordinate
ongoing physician education, and analyze antimicrobial utilization
data within the hospital. The programme should be dynamic, and
continually reassessed, adding new components or deleting
unsuccessful components over time.
To allow for accurate intra- and inter-institutional comparison,

confounding differences in expenditure related to acquisition costs
and variations in the amount of individual antibiotic used for
individual patients should be corrected by appropriate
standardization using the defined daily dose (DDD) and rates
calculated in terms of DDD per 1,000 admissions and DDD per
1,000 bed-days.
5. Is this the right time for Hong Kong to introduce ASP? Are we
too early, or are we too late, and why?
In Hong Kong, few would dispute the threat from antimicrobial

resistance and the needless expenditures associated with excessive
antimicrobial use (70). Recent surveys show that suboptimal
antimicrobial prescriptions may be commonplace in our hospitals
(71), and that they could be improved. In the two university
hospitals, one prospective study in 2003 found that 76% of
antibiotic prescriptions for patients hospitalized for exacerbation of
chronic obstructive pulmonary disease were unjustified according to
the prevailing Global Initiative for Chronic Obstructive Lung Disease
(GOLD) guidelines (71). In 2004, real-time audit of “big gun”
antibiotics in two hospitals have revealed that 20-25% of the
prescriptions were not justified or suboptimal. The most common
problems include treatment of colonization, narrower and equally
effective alternative or less toxic alternatives not being used and
inappropriate duration (Seto WH, personal communication). In
another prospective study of antibiotic combinations over a six-
month period, it was found that one of the agents was redundant in
80% of 200 prescription episodes (71).
More actions are required in areas where the antimicrobial

resistance problem is most serious. In Hong Kong, there is evidence
that antibiotic resistance in some important nosocomial pathogens
is worse than in many other parts of the world (72). In the United
States, a “Public health action plan to combat antimicrobial
resistance-action plan” was developed in 1999. In the United
Kingdom, significant progress has been made in optimizing the
clinical use of antimicrobials since 2000 in terms of governmental
directives, strategy and action plan (67;73). Recently, similar
initiatives have been launched in Taiwan and South Korea at a
national level. It is, therefore, definitely not premature to introduce
such a “universal” and “continuous” programme to the public
hospitals in Hong Kong.
Many studies have found that optimization of antibiotics in

hospitals was feasible, safe and effective. A diversity of approaches
have been reported and the experience accumulated so far indicates
a multi-faceted “stewardship” and “immediate concurrent feedback”
approach has clear advantages (62;74-81).
6. What are the disadvantages for having ASP? What problems

have been reported? Are there any arguments against having ASP
in the literature? Is there a role for an alternative mechanism?
(Table 4)
ASP involves proactive monitoring and feedbacks. One alternative

approach is “no control” (i.e. only by passive means). Such an
approach relies heavily on the distribution of national guidelines. As
discussed in detail in an international workshop, such a strategy
has not worked in the past (82). Guidelines are seldom studied
thoroughly by clinicians, and even if they are read, they rarely are
incorporated into everyday practice. On the other hand, there are
barriers and concerns to ASP that need to be addressed (Table 4).
The perception of “threatened physician autonomy” can be a
significant impediment to the effort. Previous studies and local
experiences have indicated that this is often an “emotional”
response that can be resolved by immediate concurrent feedback,
consensus building, involvement of institutional opinion leaders,
and attention to process measures (83-85). In fact, similar
programmes have been launched successfully in some Hospital
Authority hospitals for the other drugs, including the statins,
calcium channel blockers and acid suppressive agents.
Another impediment is the incorrect perception that

antimicrobial stewardship programmes are solely cost-driven
and that patient safety may be at risk. In this regard, recent
reports have emphasized the inclusion of quality indicators such as

time to reception of appropriate empirical antibiotics. Other
suggested indicators include: (a) clinical outcomes of bacteraemia
due to Gram-negative organisms (86), (b) mortality for all patients,
for those treated with antimicrobials, and for those suffering from
infections, (c) duration of hospital stay for all patients and for those
treated with antimicrobial drugs, and (d) re-hospitalization rate
within 30 days after discharge for all patients and those treated
with antimicrobial drugs (81). As in any quality improvement
programme, a financial incentive is important to secure support by
the hospital management. This is no exception for antimicrobial
stewardship programme. Good leadership and effective
communications are essential to keep members, prescribers and
patients to the appropriate focus. This could be enhanced by having
a multidisciplinary steering committee, and by regular use of data
feedback on the patterns of usages, patient outcomes, and
antimicrobial resistance data. In principle, member in the
committee should have a strong sense of commitment and
cooperation. The composition of the multidisciplinary steering
committee may be unique to each institute.
Conclusion
Considering the broader perspective, working targets are needed

and the programmes should be regularly evaluated. For a start,
each hospital will need to form a steering group and to lay down the
institutional priorities. In the literature, programme models are
available for optimizing the uses of aminoglycosides, vancomycin,
broad-spectrum antibiotics, antibiotic combinations, and for
switching therapy from intravenous to oral. It is clear that a multi-
faceted approach incorporating immediate concurrent feedback is
most likely to be successful. In order to safeguard health care
quality, the use of quality indicators and timely feedback of data are
essential. Our fight against antimicrobial resistance is going to
continue. Hence, a major challenge will be how to keep the
programmes viable and sustainable within our system in the longer
terms.

Table 3. Methods to implement antimicrobial control

1. Written hospital guidelines.
2. Educational efforts aimed at changing prescribing practices of
physicians.
3. Providing consultation from clinical microbiologist/infectious
diseases specialist.
4. Restriction of hospital formulary through the Drug and
Therapeutics Committee.
5. Utilization review with guidelines for rational and appropriate
usage.
6. Ongoing monitoring and analysis of antimicrobial agents
usage.
7. Ongoing surveillance of antimicrobial susceptibility.
8. Monitoring adherence to advice on choice of antimicrobial
agents.
9. Usage feedback to physicians.

Table 4. Potential barriers to reaching the strategic goals

Barrier Countermeasures and improvement
strategies
Ownership and accountability
1. Lack of ownership and 1. Designate responsibility and

accountability for recognizing and accountability for the process.
reporting trends. 2. Set up a multi-disciplinary team to
2. Failure to integrate work of develop a collaborative system and
laboratory, infection control, monitor results.
medical, nursing, and intensive
care-unit staffs.
Staff knowledge and practice
1. Lack of time for the laboratory 1. Ensure adequacy of laboratory and

and/or infection control staff to infection-control staffing and prioritize
generate and analyze data. activities of staff so that data can be
2. Lack of time for healthcare generated and analyzed.
providers to examine and discuss 2. Report data in an easy-to read/interpret
data and inconsistent or format and, when appropriate, include
erroneous interpretation of data data interpretation in the report.
by staff.
Physician attitudes
1. Lack of trust in the hospital 1. Use a data-driven approach to cultivate
administration trust; e.g. communicate regularly with
physicians about trends in antimicrobial
usage, cost, and resistance; feedback to
individual physicians their performance
results.
Expertise
1. Lack of expertise in biostatistics 1. Ensure availability of consultants,
(e.g. presenting trends and especially when designing analytic
analyzing data). strategy and interpreting trend data.
Reference (82)

State-of-the art: Limiting antimicrobial resistance

1. US surveys: 22-65% usage of antibiotics in the hospitals is
inappropriate.
2. Outbreaks of multi-resistant bacteria, including those that

persist despite apparently adequate infection control measures,
can be limited effectively by antibiotic programme directed at
judicious use of antibiotics.
3. While restriction of an individual antibiotic (such as cefotaxime or

ceftazidime) has been reported to be useful in controlling
outbreaks of drug-resistant bacteria, the general consensus is
that the main focus should be directed at the rational use of all
classes of antibiotics rather than merely restricting the use of
individual drugs (6;86-96).
Over-prescription of third generation cephalosporins and

vancomycin
Experience from several overseas centres suggests that over-
prescription of third generation cephalosporins and glycopeptides are
closely associated with the selection and dissemination of ESBL-
producing Enterobacteriaceae, de-repressed AmpC-type mutant among
Enterobacter cloacae, Citrobacter freundii, Serretia marcescens, MRSA,
and VRE.
1. Cephalosporin use has been identified as a risk factor for

enterococcal colonization and superinfection, as well as for
antibiotic-associated diarrhea, the main reason for oral
vancomycin (97;98).
2. Significant risk factors for colonization or infection with VRE were

prior antibiotic use (p=0.04), the previous use of third-generation
cephalosporins (p=0.03), and the previous use of parenteral
vancomycin (p=0.002). This data was obtained from 7 hospitals
including primary and tertiary care facilities (200-700 beds) (99).
3. In the Cornell University Medical College, New York, it was found

that the duration of hospitalization, intrahospital transfer
between floors, use of antimicrobials (i.e. vancomycin and third
generation cephalosporins), and duration of vancomycin use (t7

days) were independently associated with VRE infection or

colonization (100).
4. Ten weeks after the introduction of cefotaxime, resistant

Enterobacter cloacae could be isolated from stool cultures in an
increasing proportion of patients and septicaemia developed in 6
cases (101).
5. In 6 US hospitals, previous administration of third-generation

cephalosporins was more likely to be associated with multi-
resistant Enterobacter isolates in an initial positive blood culture
(69%) than was administration of antibiotics (20%) that did not
include a third-generation cephalosporins (p<0.001) (102).
6. Resistance to third generation cephalosporins among

Enterobacter spp, Citrobacter freundii, Morganella morganii,
Serratia marcescens and Providencia spp. has become widespread
both locally within hospitals and nationally. This trend has been
shown to correlate closely with the extent of usage of some third
generation cephalosporins (1;103).
Decreased antibiotic resistance after changes in

antibiotic use
No simple answer exists on the control of multi-drug resistant
bacteria. The traditional approach slanted heavily on infection control
measures, which are obviously important but can be difficult to
implement. When audited, compliance with hand hygiene measures
has been consistently low (<40%) (104). Outbreaks of multi-drug
resistant bacteria have continued despite apparent adherence to
“standard” hygienic measures. In recent years, there has been renewed
interest on the strategic use of antibiotics as a measure for prevention
or control of antimicrobial resistance (94). In fact, several studies have
demonstrated that strategic use of antibiotics (so far, only class
restriction of the cephalosporins have been evaluated to a significant
extent) can lead to:
1. Less multi-resistant de-repressed AmpC-type Enterobacter spp.

An outbreak of infections by multi-resistant Enterobacter spp.
disappeared after use of cefotaxime was discontinued in the unit.
2. Less ESBL-producing Enterobacteriaceae. Literature on

antimicrobial strategies as an intervention to reduce ESBL-
producing K. pneumoniae was summarized in Table 5. In a case-
control study, the use of beta-lactam/beta-lactamase inhibitor

combination was shown to be a protective factor (105).
3. Less vancomycin-resistant enterococci. Two studies reported on

the successful control of VRE outbreaks by changing antibiotic
usage (92;106). In one medical centre (92) , the antibiotic
formulary was altered by restricting the use of cefotaxime and
vancomycin and adding beta-lactamase inhibitors to replace
third-generation cephalosporins. After 6 months, the average
monthly use of cefotaxime, ceftazidime, vancomycin, and
clindamycin had decreased by 84%, 55%, 34% and 80%
respectively (p<0.02). The point prevalence of faecal colonization
with VRE decreased from 47-15% (p<0.001). In another
haematologic unit (106), acquisition of VRE paralleled the use of
ceftazidime as empirical therapy for neutropenic fever. Phase 1:
ceftazidime as empirical therapy, VRE carriage rate was 57%.
Phase 2: piperacillin-tazobactam replaced ceftazidime as
empirical therapy, VRE carriage decreased to 8%. Phase 3:
ceftazidime re-introduced as empirical therapy, VRE carriage
increased to 36%. Those who are interested in the experimental
data that might explained this observed relation between VRE,
cephalosporins and BLBLI should refer to a recent review by Rice
et al (107).

Table 5. Summary of published data on antimicrobial strategies as an intervention to reduce

ESBL resistance.
Year period (Ref) Setting (type of study) Intervention/result Outcome Other observations
199499 (108) Epidemic rise in ESBL in K. Minimize use of ceftazidime ESBL rate remain
pneumoniae from 6-28% within 1 (marked and sustained p); <10% next 4 years
year in a medical centre addition of piperacillin-
(intervention study) tazobactam to formulary (usage n)
199398 (109) Spread of VRE in one institute Use of BLBLI emphasized and the Mean incidence of Cefotaxime-resistant
continued despite infection control use of 3GCs, vancomycin and CRKP p by 34% Acinetobacter n by
measures (intervention study). clindamycin restricted; addition of >100%
ampicillin-sulbactam and
piperacillin-tazobactam to
formulary.
198990 (110) Outbreak of CRKP in one medical Ceftazidime was replaced by CRKP p from >30%
centre. Use of ceftazidime n 600% in imipenem. to <10%
the 2 years before outbreak
(intervention study).
199395 (111) A clonal outbreak of ESBL- Restriction of 3GC (usage p by ESBL carriage p from
producing K. pneumoniae in an ICU 87% after intervention). 33 to 40% to 0%.
(intervention study).
199596 (112) An outbreak of ESBL-producing K. Class restriction of cephalosporins CRKP ESBL p by Imipenem-resistant
pneumoniae in a hospital since (usage p by 80% after 44%. P. aeruginosa n by
1990 (intervention study). intervention). Usage replaced by 69%
imipenem.
1996 (113) Clonal outbreak of CRKP in hospital Physician education on Hospital A: CRKP p % KP resistant to
A. Polyclonal outbreak of CRKP in association of p ceftazidime use from 22 to 15%. BLBLI also p (36 to
hospital B (intervention study). and p CRKP. Use of ceftazidime p Hospital B: CRKP p 19% in A and 22 to
by 71% (hospital A) and 27% from 10 to 5%. 14% in B)
(hospital B).
3GC, third generation cephalosporins; BLBLI, beta-lactam/beta-lactamase inhibitor; CRKP, ceftazidime-resistant K. pneumoniae.

Classification of therapy
Empirical therapy
In the clinical situation of “empirical use”, the antimicrobial(s) is/are
used as initial therapy directed to eradicate the most likely pathogens.
Before initiation of antimicrobials, appropriate specimens for stains
and culture of microorganisms should be obtained. Results of
identification and susceptibility of microorganisms are likely to be
available in the following 48 to 72 hours. The use of broad-spectrum
antibiotics or combination therapy is usually necessary to cover the
different organisms capable of causing an infection. In general, the use
of agents in this situation should not extend beyond the time required
to obtain results of cultures and susceptibility.
Choice of agent(s): based upon adequate coverage of the potential
pathogens of the potential infection sites and the anticipated
antimicrobial susceptibility patterns of the bacterial isolates.
Recommendations of empirical therapy for some common infections
are outlined in Part IV.
Known-pathogen therapy
In the clinical situation of known pathogen use, the antimicrobial(s) is
/are used when the microbiology laboratory has identified the micro-
organism causing the infection and the susceptibility pattern is
known. If during empirical use, the patient is started on combination
therapy or broad spectrum antibiotics, the antimicrobial spectrum
should be narrowed to cover the micro-organisms identified as the
aetiologic agent. Streamlining from broad-spectrum to specific, narrow
spectrum antimicrobials helps to avoid colonization with resistant
organisms and superinfections. In the absence of allergy or other
contraindications, the agent (appropriate for the site and type of
infection) with the narrowest spectrum in a group or a list of candidate
drugs should be used.
It should be noted that the skin and mucous membrane surface of the
hospitalized patient are often colonised with nosocomial bacteria (such
as MRSA, E. coli, Klebsiella spp, etc.), systemic antimicrobial therapy
(both IV and PO) should not be administered in an attempt to
eradicate these micro-organisms.

Switch therapy-conversion from IV to PO

In the clinical situation of switch therapy use, PO antimicrobials
replace IV usage for completion of therapy. IV is almost always
employed in serious infections to ensure maximal serum/tissue levels.
With few exceptions such as meningitis, infective endocarditis, the
majority of patients with infections do not require completion of the
antimicrobial course with IV therapy. The following criteria have been
developed for transition from IV to PO antimicrobial (114;115):
1. Patient with no clinical indication for IV therapy.
2. Patient is afebrile for at least 8 hours.
3. The WBC count is normalizing (falling towards or <10x109/L).
4. Signs & symptoms related to infection are improving.
5. Patient is not neutropenic (neutrophil count >2 x109/L).
6. Patient is able to take drugs by mouth (non-NPO).
7. Patient with no continuous nasogastric suctioning.
8. Patient with no severe nausea or vomiting, diarrhea,

gastrointestinal obstruction, motility disorder.
9. Patient with no malabsorption syndrome.
10. Patient with no pancreatitis or active gastrointestinal bleeding or

other conditions that contraindicated to the use of oral medications.

Table 6. Strategies for optimization of antimicrobial therapy

Stages in the management of infection Strategies for optimization
Empirical therapy (ET)
x Document the presence of infection x Education
x Likely pathogens? x Collection and analysis of local
x Likely susceptibility pattern data
x Community- or hospital-acquired x Pocket reference guide
infection?
x Monotherapy or combination therapy?
When culture and susceptibility results are available
Known-pathogen therapy (KPT)

x Narrowest spectrum according to x Cascade reporting of sensitivity
laboratory results x Daily review of prescription of
x Follow guidelines on the judicious use of “big gun” antibiotics by ASP
ceftazidime, imipenem/ertapenem/ team.
meropenem, vancomycin/teicoplanin/ x Daily reporting of deviations
linezolid from guidelines to clinical
microbiologist/ID physician
x ASP team to give daily
immediate concurrent feedback
(ICF) to prescribers.
Switch therapy (116;117)
x A switch from intravenous to oral therapy x Daily review of patients on IV
x Criteria for switch therapy “big gun” antibiotics by ASP
x Clinical diagnosis compatible with oral team
therapy x Daily recommendation for
x Patient has functioning gastrointestinal “switching” by ASP team
tract
x Patient is afebrile (for >24h)
x Signs and symptoms related to infection
are improving or resolved
x The WBC count is normalizing
Stop therapy
x Type of infection z Education
x Clinical responses
x Follow-up culture results where
appropriate

Part III: Selected Antimicrobial agents
Part III: Guidelines for selected antimicrobials use

Vancomycin
Situations in which the use of vancomycin/teicoplanin is
appropriate (6;83)
1. Treatment of serious infections caused by beta-lactam resistant
Gram-positive bacteria (e.g. MRSA, coagulase-negative
staphylococci).
2. Treatment of infections caused by Gram-positive bacteria in
patients who have serious allergies to beta-lactam antimicrobial
agents (e.g. anaphylactic reaction, Stevens-Johnson syndrome).
3. When Clostridium difficile colitis fails to respond to metronidazole
therapy or is severe and life-threatening.
4. As prophylaxis for endocarditis following certain procedures in-
patients at high risk for endocarditis; according to
recommendation from the American Heart Association. (e.g. as
prophylaxis for genitourinary or gastrointestinal procedures in
moderate or high-risk patients allergic to ampicillin/amoxicillin).
5. As prophylaxis for major surgical procedures involving the
implantation of prosthetic material or devices in known carriers
of MRSA. For elective procedures, daily washing of skin and hair
with a suitable antiseptic soap (e.g. 4% chlorhexidine liquid soap)
and topical treatment of the anterior nares with nasal mupirocin
ointment (for 5 days) are recommended before the procedures.
Vancomycin may be less effective in preventing surgical wound
infection due to methicillin-sensitive staphylococci (118).
Situations in which the use of vancomycin/teicoplanin are not

advised
1. Treatment of MRSA nasal carriage or colonization at other sites
such as the isolation of MRSA from
x Surface swab of superficial wounds
x Surface swab of chronic ulcers
x Surface swab of pressure ulcers
2. Routine surgical prophylaxis other than in a patient who has
serious allergy to beta-lactam antimicrobial agents.
3. Routine empirical antimicrobial therapy for neutropenic fever
(except as recommended by the IDSA 2002 guidelines for the use
of antimicrobial agents in neutropenic patients with unexplained
fever).

4. Treatment in response to a single blood culture positive for

coagulase-negative staphylococci, if other blood cultures taken
during the same time frame are negative.
5. Continued empirical use of presumed infections in patients
whose cultures (blood, joint fluid, peritoneal fluid, pus, etc), are
negative for beta-lactam-resistant Gram-positive bacteria (e.g.
MRSA).
6. Systemic or local (e.g. antibiotic lock) prophylaxis against
infection (or colonization) of indwelling (central or peripheral)
intravascular catheters.
7. As routine prophylaxis, before insertion of Hickman/Brovac
catheter or Tenckhoff catheter.
8. As part of the regimen for selective digestive tract
decontamination.
9. Primary treatment of Clostridium difficile colitis, except when it is
severe and life-threatening.
10. Routine prophylaxis for patients on continuous ambulatory
peritoneal dialysis or haemodialysis.
11. Treatment (e.g. chosen for dosing convenience) of infection
caused by beta-lactam-sensitive Gram-positive bacteria in
patients who have renal failure.
12. Use of vancomycin solution for topical application (e.g. to burn
wound, ulcers) or irrigation (e.g. of T-tube, drains).
Vancomycin dosage in special situations and therapeutic drug

monitoring
1. In adults, the standard recommended dose of vancomycin is 30
mg/kg/day (IV 1 g q12h or IV 0.5 g q6h in a normal 70 kg
person).
2. Therapeutic drug monitoring (TDM)
Vancomycin exhibits time-dependent killing. Efficacy can usually
be assumed if the trough concentration is sufficiently above the
MIC of the infecting organism (i.e. best if vancomycin levels at
site of infection are maintained above MIC throughout the dose
interval). MIC of most susceptible organisms (e.g. MRSA) ranges
1-2 Pg/mL.
Routine TDM is not indicated in most patients because
vancomycin pharmacokinetics are sufficiently predictable that
safe and effective vancomycin dosage regimens (giving trough
levels 5-10 Pg/mL and peak levels <40 mg/mL) can be

constructed on the basis of patient's age, weight and estimated
renal function.
Indications for TDM
(a) Renal impairment (rapid change/unstable renal function
making it difficult to estimate dose)
(b) ICU patients co-treated with dopamine and/or dobutamine
(119)
(c) Severe burn (120)
(d) Morbid obesity (121)
(e) Spinal cord injury (122)
When TDM is indicated, check only trough level. There is no solid
data to support the widely referenced trough range of 5-10 Pg/mL
and accordingly, serum concentrations have been selected
somewhat arbitrarily, based on pharmacology, retrospective
studies, case reports and personal opinions. Due to the poor
penetration of vancomycin to certain lung tissues, the 2005 ATS
guideline recommend trough levels of 15ï20 Pg/mL for treatment
of MRSA hospital-acquired pneumonia (123). Current literature
does not support peak concentration measurement (124).
3. Dosage table/nomogram in patients with impaired renal function
(Table 7)
x An initial single dose of 15 mg/kg should be given to achieve
prompt therapeutic serum concentration. Subsequent daily
maintenance dose is to be determined according to dosage
table/nomogram.
x The dosage table/nomogram is not valid for functionally
anephric patients on dialysis. For such patients, the dose
required to maintain stable concentrations is 1.9 mg/kg/day
(~130 mg/day for a 70 kg person).
x For patients with marked renal impairment, it may be more
convenient to give maintenance doses of 0.25 g to 1 g every 3-7
days.

Table 7. Dosage table for vancomycin

Creatinine clearance ( mL/min) Vancomycin dose (mg/24 h)
100 1,545
90 1,390
80 1,235
70 1,080
60 925
50 770
40 620
30 465
20 310
10 155
Adapted from vancomycin package insert July 2004 .
4. Vancomycin in morbidly obese patients (121;125) (Table 8)

x Serum clearance of vancomycin in morbidly obese patients
was 2.3-2.5 times higher than that observed in non-obese
subjects (121;126).
x In a study of 24 morbidly obese patients, the mean (±SD)
vancomycin dose required to achieve steady state peak 25-35
Pg/mL and trough 5-10 Pg/mL were 1.9 g (±0.5 g) q8h.

Table 8. Calculation of vancomycin dosage for morbidly obese

patient
Scenario: Female/30yr,
body weight 200 kg,
Steps Calculation
height 1.8 m, serum
creatinine 80 Pmol/L
Determine if the patient is TBW/IBW ratio: 200/70.7 = 2.8
morbidly obese
0.81.25 = normal
>1.251.9 = obese
>1.9 = morbid obesity
Determine dose of 30 mg/kg TBW/day 6 g per day if normal
vancomycin renal function.
(administer as IV 2 g q8h;
infuse each 2 g dose over
at least 2 h)
Estimate creatinine Cockcroft-Gault formula
clearance (CrCl) not accurate in morbidly
obese patients. The
Salazar-Corcoran
equation appears to give
the least biased estimate
of CrCl
Monitor trough level Target trough at 5-10 Adjust dosing interval
Pg/mL according to trough level
Equations:
1. Ideal body weight (IBW)
x IBW for male = 50 kg + 0.9 kg for each cm over 152 cm (2.3 kg for each
inch over 5 feet)
x IBW for female = 45.5kg + 0.9 kg for each cm over 152 cm (2.3 kg for
each inch over 5 feet)
2. Salazar-Corcoran equation (for estimate of creatinine clearance in morbidly
obese patients):
Male patient, calculate CrCl as follows:
(137age in years) u (TBW in kg u 0.285) + (12.1 u height in meter)
0.58 u serum creatinine in Pmol/L
Female patient, calculate CrCl as follows:

(146age in years) u (TBW in kg u 0.287) + (9.74 u height in meter)
0.68 u serum creatinine in Pmol/L
a TBW, total body weight

Quinupristin/dalfopristin and linezolid
1. Indications for linezolid (Zyvox) or quinupristin/dalfopristin

(Synercid):
a. Infections by vancomycin-resistant enterococci (VRE) or S.

aureus with reduced susceptibility to vancomycin (e.g. VISA)
b. Infections by methicillin-resistant Staphylococcus aureus in the

case of vancomycin failure (e.g. unexplained breakthrough
bacteraemia) and/or serious allergy. In these complicated
circumstances, the opinion of a specialist (microbiologist or ID
physician) should be sought.
2. Most VRE (n=11) identified in Hong Kong so far are susceptible to

linezolid (both E. faecalis and E. faecium) at d4 Pg/mL and
quinupristin/dalfopristin (E. faecium only, at d1 Pg/mL) (19).

Table 9. Comparison of linezolid and quinupristin/dalfopristin

Linezolid Quinupristin/dalfopristin
FDA Yes/2000 Yes/1999 (for serious infections
approval/year associated with vancomycin-
resistant E. faecium)
Registration in Yes No
Hong Kong
Formulary IV/PO. Bioavailbility of PO Only IV
linezolid is ~100%.
Usual dose IV/PO 600 mg q12h IV 7.5 mg/kg q8h (infuse over 1
h in D5)
Central venous No Yes
catheter for
administration
Activity vs. VRE both vancomycin-resistant Only vancomycinresistant E.

E. faecalis and E. faecium faecium a
Effect on Nil (No effect on 1A2, 2C9, Inhibit 3A4 isoenzyme strongly,
cytochrome P450 2C19, 2D6, 2E1, 3A4) hence interactions with
midazolam, nifedipine,
astemizole, terfenadine,
cyclosporin (must monitor
level), tacrolimus
Monoamine Yes (a weak, reversible, Nil (No effect on MAO).

oxidase (MAO) nonselective MAO inhibitor),
inhibition hence potential for
interactions with adrenergic
and serotonergic drugs.
Side effects Thrombocytopenia (related Phlebitis (high incidence if
to duration of treatment; administered via peripheral
incidence 0.3-10%; need vein); arthralgia/myalgia (dose
monitoring if treated for >7d) related; incidence 1.3-33%)
General Compatible with both D5 Form precipitate with saline.
compatibility and saline. DO NOT flush with saline or
heparin after quinupristin/
dalfopristin administration.
Renal No adjustment in dose No adjustment in dose required

impairment required in pt. with renal in pt. with renal impairment or
impairment. Give dose after undergoing dialysis.
HD.
Data from package insert of Zyvox and Synercid.
a
All E. faecalis isolate (including vancomycin-resistant E. faecalis) are intrinsically
resistant to quinupristin/dalfopristin.

Ceftazidime
Indications for using ceftazidime (Fortum) (127)
1. Empirical therapy of neutropenic fever, either as monotherapy or
in combination with an aminoglycoside (128).
2. Therapy of infection by Burkholderia pseudomallei infection
(melioidosis).
x Probable case (compatible chest X-ray plus a melioidosis titre
of t 1/640) or definite case (isolation of B. pseudomallei).
3. Known pathogen therapy of documented infection by susceptible
Pseudomonas aeruginosaa, such as:
(a) Bacteraemia with isolation of Pseudomonas aeruginosa from
blood culture.
(b) Deep-seated infection with isolation of Pseudomonas
aeruginosa from normally sterile body site or fluid (CSF,
peritoneal fluid, pleural fluid, joint fluid, tissue, pus, etc) a.
(c) Nosocomial pneumonia, as defined by CDC guidelines
(appendix), with isolation of Pseudomonas aeruginosa in a
significant quantity, from a suitably obtained, good quality
respiratory tract specimenb.
Footnotes
a For serious P. aeruginosa infection, an anti-pseudomonal beta-lactam should be
given in combination with an aminoglycoside such as gentamicin given once daily
for the initial 3 to 5 days to achieve synergistic killing. For susceptible isolates;
anti-pseudomonal beta-lactams in decreasing order of preference: piperacillin or
piperacillin-tazobactam or ticarcillin-clavulanate > cefoperazone or cefoperazone-
sulbactam or cefepime or ceftazidime > imipenem or meropenem.
b Colonization of the respiratory tract by P. aeruginosa, especially in mechanically
ventilated patients is common. Antimicrobial therapy of colonization is not
indicated. Isolation of P. aeruginosa at the indicated quantity and specimen type is
suggestive of infection rather than colonization (in descending order of clinical
significance):
1. 102-103CFU/mL or moderate/heavy growth for protected specimen brush.
2. 103-104 CFU/mL or moderate/heavy growth for bronchoalveolar lavage.
3. Moderate/heavy growth for tracheal/endotracheal aspirate specimens with ++
to +++ white cells and absent/scanty epithelial cells.
4. Expectorated sputum (as defined by the American Society for Microbiology)
with >25 WBC/low power field and <10 epithelial cells/low power field.

Situations/conditions in which ceftazidime is not advised

1. Treatment of colonization by Pseudomonas aeruginosa such as
the isolation of these organisms from
2. Empirical or continued treatment of suspected or confirmed
infection by S. pneumoniae including bacteraemia, pneumonia
and meningitis.
x Infection outside the central nervous system by both penicillin-
susceptible and penicillin-non-susceptible (MIC <4 Pg/mL), the
drugs of choice are penicillin G (standard or high dose) or
amoxicillin or cefotaxime or ceftriaxone (refer to known-
pathogen therapy chart).
3. Empirical or continued treatment of infection by
Enterobacteriaceae such as E. coli and Klebsiella spp. susceptible
to other antimicrobial agents.
x For susceptible isolates the beta-lactam of choice in
descending order of preference are as follows: ampicillin or
amoxicillin > ampicillin-sulbactam or amoxicillin-clavulanate >
cefuroxime > ceftriaxone or cefotaxime.
4. Empirical therapy of community-acquired pneumonia, including
patients hospitalized in the ICU for serious pneumonia and
patients with structural disease of the lung (adapted from
Infectious Disease Society of America 1998).
x Other agents with activity vs. P. aeruginosa and S. pneumoniae
preferred because ceftazidime (while active vs. P. aeruginosa) is
not useful vs. penicillin-non-susceptible S. pneumoniae.
5. Empirical or continued treatment of anaerobic or mixed infection
in the head and neck, biliary, pancreatic, gastrointestinal,
peritoneal, pelvic or peritoneal regions.
x Ceftazidime has virtually no activity against most of the
medically important anaerobes.
6. Empirical or continued treatment of patients with colonization or
infection by Enterobacteriaceae such as E. coli, Klebsiella spp.
and Enterobacter spp. known to produce ESBL.
x Applies irrespective of whether ceftazidime was tested or not
and also irrespective of the apparent in vitro susceptibility of
the isolate to ceftazidime.

7. Empirical or continued treatment of infection by S. aureus (both
MSSA and MRSA).
8. Empirical or continued treatment of infection by all enterococci
such as E. faecalis and E. faecium.
9. Empirical treatment for community-acquired meningitis.

Imipienem/meropenem/ertapenem
Indications for using imipenem/meropenem/ertapenem
1. Therapy of infections attributed to ESBL-producing bacteria
(such as E. coli or Klebsiella spp. ) such as:
x Bacteraemia with isolation of ESBL-producing bacteria from
blood culture.
x Deep-seated infection with isolation of ESBL-producing
bacteria from normally sterile body site or fluid (CSF,
peritoneal fluid, pleural fluid, joint fluid, tissue, pus, etc).
x Nosocomial pneumonia, as defined by CDC guidelines, with
isolation of ESBL-producing bacteria in a significant quantity,
from a suitably obtained, good quality respiratory tract
specimensa
2. Empirical therapy of neutropenic fever in high risk patients. (As
Ertapenem has no anti-pseudomonal activity, it should not be
used as empirical therapy for neutropenic fevers or for treatment
of presumed/confirmed infections by the non-fermenters such as
Pseudomonas aeruginosa and Acinetobacter.)
Footnotes
a Colonization of the respiratory tract by ESBL-producing bacteria, especially in
mechanically ventilated patients is common. Antimicrobial therapy of colonization
is not indicated. Isolation of ESBL-producing bacteria at the indicated quantity
and specimen type is suggestive of infection rather than colonization (in
descending order of clinical significance):
1. 102-103 CFU/mL or moderate/heavy growth for protected specimen brush.
2. 103-104 CFU/mL or moderate/heavy growth for bronchoalveolar lavage.
3. Moderate/heavy growth for tracheal/endotracheal aspirate specimens with
++ to +++ white cells and absent/scanty epithelial cells.
4. Expectorated sputum (as defined by the American Society for Microbiology)
with >25 WBC/low power field and <10 epithelial cells/low power field.

Situations/conditions in which imipenem/meropenem/ertapenem

is not advised
1. Treatment of colonization by ESBL-producing bacteria such as
the isolation of these organisms from.
2. Empirical therapy of most community-acquired infections
including pneumonia, appendicitis, cholecystitis, cholangitis,
primary peritonitis, peritonitis secondary to perforation of
stomach, duodenum or colon, skin/soft tissue infections, etc.
3. As known-pathogen therapy for infections caused by organisms
susceptible to other beta-lactams.

Once daily aminoglycosides

1. Once daily aminoglycoside (ODA) dosing is as effective as
multiple-daily dosing in most clinical settings. The former dosing
probably results in a lower risk of nephrotoxicity than the latter.
With ODA, any differences in the relative nephrotoxicity of the
aminoglycosides are likely to be small. Nonetheless, there is
considerable confusion on the dose and how to monitor serum
aminoglycoside levels when using ODA dosing.
2. Dosing to be based on actual body weight unless the patient is
morbidly obese (i.e. 20% over ideal body weight, IBW).
Aminoglycoside dosing weight for morbidly obsess

patient
= ideal body weight + 0.4 (actual body weight - IBW).
Formula for calculation of ideal body weight is as follows:
Ideal body weight for male = 50 kg + 0.9 kg for each cm
over 152 cm (2.3 kg for each inch over 5 feet)
Ideal body weight for female = 45.5 kg + 0.9 kg for each cm
over 152 cm (2.3 kg for each inch over 5 feet)
3. For patient with impaired renal function, give the first dose
according to body weight as above. Subsequent frequency of
administration (of the same dose) to be based on the estimated
creatinine clearance of the patient according to the following
table.
Cockcroft-Gault formula
To estimate creatinine clearance, calculate as follows
Creatine clearance for male patient (mL/min) = (140-age) x
1.2 x ideal body weight (kg) /serum creatinine (Pmol/L)
(Female: 0.85 u above value)
(Unit conversion for serum creatinine: mg/dL x 88.4 =
Pmol/L)

a
CrCl Initial dosing interval
(mL/min)
!60 q24h
40-60 q36h
20-40 q48h
<20 Follow serial levels to determine time of
next dose (level <1 Pg/mL)
a
At present, the dosage of aminoglycoside to use in a ODA strategy
has not been clearly determined. Dosages for gentamicin, tobramycin
and netilmicin have ranged from 3 to 7 mg/kg, and amikacin dosages
have ranged from 11 to 30 mg/kg. On the basis of local experiences
and a recent consensus meeting, the following doses are recommended
for initial therapy in local Chinese: for gentamicin and tobramycin, 3.5
mg/kg; netilmicin, 4.4 mg/kg and amikacin, 15 mg/kg (129).
4. Therapeutic drug monitoring (TDM) (130-132)

Routine TDM not indicated in patients under the following
conditions:
(a) Receiving 24-h dosing regimen,
(b) Without concurrently administered nephrotoxic drugs (e.g.
vancomycin, amphotericin B, cyclosporin),
(c) Without exposure to contrast media,
(d) Not quadriplegic or amputee,
(e) Not in the ICU,
(f) Younger than age 60 yr
(g) Duration of planned therapy less than 5 to 7 days.

If Therapeutic drug monitoring is indicated (e.g. due to impaired

renal function), check level and interpret the result as follows:
a) For once daily (extended-interval) dosing, obtain a single blood
sample after the first dose between 6-14 h after the start of the
infusion. Do not check pre- and post-dose.
b) Write down the time in number of hours after last dose in request
form (e.g. 8 h post-dose). This is essential for result
interpretation.
c) When result becomes available, plot the value on the Hartford
normogram (Table 10) and work out the appropriate dosing
interval by the following table. With this method, the size of each
dose need not be reduced.
Post-dose level Dosing interval

Level falls in the area Dose at an interval of every
designated q24h 24h
designated q36h 36h
designated q48h 48h
Level on the line Choose the longer interval
Level off the normogram at Stop the scheduled therapy,
the given time obtain serial levels to
determine the appropriate time
of the next dose

Table 10. Hartford Hospital once-daily aminoglycoside normogram

for gentamicin and tobramycin
The Hartford normogram has not been validated in the following
category of patients: paediatrics, pregnancy, burns (>20%), ascites,
dialysis, Enterococcal endocarditis (51).

Summary of selected antifungal agents

Table 11. General patterns of antifungal susceptibility
Fluconazole Itraconazole 5-Flucytosine Amphotericin B Voriconazole Caspofungin
C. albicans S S S S S S
(MIC 0.5 Pg/mL)
C. tropicalis S S S S S S
C. glabrata S-DD to R S-DD to R S S-I S S
C. krusei R S-DD to R I-R S-I S S
C. lusitaniae S S S S-R S S
(MIC 0.5 Pg/mL)
C. parapsilosis S S S S S less active
C. guillermondii S S S S S less active
MIC 2 Pg/mL)
Cryptococcus S S S S S R (MIC 32
neoformans Pg/mL)
Trichosporon S S ? I S R
Fusarium R Some spp. ? I to R + R in vitro

R in vitro (mean MIC 60-
70 Pg/mL)
Pseudallescheria ? + ? - ? S (mean MIC 1.3
Pg/mL)
Asperigillus – + + + ++ ++ (mean MIC
(mean MIC 0.1-0.15 Pg/mL)
0.4 Pg/mL)
Mucor R R NA + R R
S, susceptible; S-DD, susceptibility is dose-dependent; R, resistant

Table 12. Comparison of susceptibility of selected fungi to the azoles

Organism (no. of Range MIC that can MIC that can
isolates tested) (133- (Pg/mL) inhibit 50% of all inhibit 90% of all
135) tested isolates tested isolates
(Pg/mL) (Pg/mL)
C. glabrata (n=217)
Fluconazole 0.25ï128 16 64
Itraconazole 0.06ï8 1 4
Voriconazole 0.03ï8 0.5 2
C. krusei (n=33)
Fluconazole 8ï128 64 64
Itraconazole 0.12ï2 1 2
Fluconazole-
resistant C. albicans
(n=12)
Fluconazole 64ï128 >128 >128
Itraconazole 1ï8 >8 >8
Voriconazole 0.25ï8 >8 >8
A. fumigatus (n=284)
Amphotericin B 0.125ï1 0.25 0.5
Itraconazole 0.125ï4 0.5 1
Voriconazole 0.125ï2 0.25 0.5
Amphotericin-
resistant A.
fumagitus (n=15)
Itraconazole 0.25ï0.5 0.25 0.5
Itraconazole-
resistant A.
fumigatus (n=15)
Amphotericin B 0.25ï1 0.5 0.5

Table 13. Mechanisms of antifungal action.

Primary mode of Target
action
Azoles: (fluconazole, Inhibit ergosterol Fungal cytochrome P-450
itraconazole, biosynthesis dependent 14 D-sterol
voriconazole) demethylase
Caspofungin Inhibit fungal cell wall Fungal E-1,3-glucan
glucan synthesis synthase
Amphotericin B Bind to and make Fungal cell membrane
fungal cell membrane
‘leaky’

Table 14. Comparison of selected pharmacokinetic parameters for the azoles and caspofungin
Fluoconazole Itraconazole Voriconazole Caspofungin
Trade name Diflucan Sporanox Vfend Cancidas
Oral >80% Capsule: 30-55% 90% Only IV
bioavailability Solution: 60-80%
Cmax 10.2 0.2-0.4 mg/L after 2-4 h of 2 mg/L after 250 oral 10 mg/L end infusion
200 mg oral
Time to Cmax 2-4 4-5 1-2 -
(hr.)
CSF 50-94% <1% 20-50% Unknown (Very low)
penetration
Plasma half-life 22-35 24-42 6-24 9-11 (terminal half-life 40-50
(hr.) hours)
Tissue Widely Levels in body fluids/CSF Widely distributed into body Widely distributed; highest
distribution distributed in low; concentrations in lung, tissues & fluid including brain concentration in liver.
most tissues liver & bone 2-3 times > & CSF
including CSF. serum. High concentration
in stratum corneum due to
drug secretion in sebum.
Principal route Renal Hepatic Hepatic Hepatic
of elimination
Active drug in 80 <1 2% 1%
urine (%)
Dosage Oral or i.v. 50- 200-400mg/day Adult, oral, 200-400 mg 12- i.v. infusion of 70 mg loading,
400 mg/day [In life-threatening hourly for 24 h, then, 100-200 then 50 mg daily
depending on situations, a loading dose mg 12-hourly;
indications should be used whether i.v. 6mg/kg 12 hourly for 24 h,
given oral capsule or IV, then 4 mg/kg 12 hourly
e.g. 200mg PO tds for first
3 days]
Renal Reduce dose; Usual dose. At CFR <10 No dose adjustment need with No dose adjustment needed. Not
insufficiency removed by ml/min, some recommend oral voriconazole. Avoid iv removed by hemodialysis
haemodialysis decrease dose 50% voriconazole in renal failure.
Hepatic - avoid ? avoid Reduce dose to 35 mg daily (after
insufficiency the 70 mg loading dose) in
moderate (Child-Pugh score 7-9).
No data on usage in patient with
severe hepatic failure

Table 15. A suggested scheme for systemic antifungal agents

First-Line Alternative Comments
INVASIVE CANDIDIASIS
Neutropenic or critically Amphotericin B Fluconazole or caspofungin Consider agent other than
ill (if intolerant of caspofungin for serious infection
amphotericin B) due to C. guilliermondii & C.
parapsilosis (136)
Stable and Fluconazole Amphotericin B Evidence is mainly for C.
nonneutropenic albicans. It also works for C.
parapsilosis and C. tropicalis
INVASIVE ASPERGILLOSIS
Voriconazole Amphotericin B (1-1.5 Efficacy of voriconazole is clear
(documented invasive mg/kg) or caspofungin for for A. fumigatus. In the case of
aspergillosis) documented non-fumigatus non-fumigatus aspergillus,
aspergillosis. treatment response requires
confirmation with a larger data
set (137).
Note: The diagnosis and treatment of systemic fungal infection is complicated. The newer anti-fungal agents (e.g.
itraconazole, voriconazole, caspofungin) should be used at the specific advice of a specialist.

Part IV: Empirical therapy
Part IV: Recommendation for the empirical therapy of

common infections

Usual organisms Preferred regimens Alternatives Special considerations /

[usual duration of treatment]
Musculoskeletal
infections
Septic arthritis, S. aureus; IV cloxacillin + IV cefazolin x Urgent diagnostic tapping
adult Streptococci, N. ampicillin for gram stain to guide
gonorrhoeae therapy.
x If smear reveal Gram-
negative cocci or bacilli:
ceftriaxone or cefotaxime to
replace cloxacillin..
x Factors suggest N.
gonorrhoeae etiology:
sexually active
teenager/adult r rash..
Osteomyelitis, S. aureus IV cloxacillin IV cefazolin x Occasionally Salmonella
haematogenous, spp..
adult x Often vertebral.
x IVDU: S. aureus (vertebral);
P. aeruginosa (ribs,
sternoclavicular joint).

Diabetic foot
infection
(a) Previously S. aureus, beta- Ampicillin- Clindamycin or [14 days]
untreated, no haemolytic sulbactam (138) or cephalexin
osteomyelitis Streptococci amoxicillin-
clavulanate
(b) Chronic, Polymicrobial: PO levofloxacin/ Ticarcillin- Cultures from ulcers
recurrent, limb aerobes + ciprofloxacin + PO clavulanate or unreliable.
threatening anaerobes clindamycin or piperacillin- Early radical debridement to
ampicillin- tazobactam obtain tissue for culture; to
sulbactam (138) exclude nercotizing fasciitis
and for cure.
Ability to insert probe to bone
suggest concomitant
osteomyelitis.
Skin and soft tissue
infections
Erysipelas or Groups A, B, C, G (IV penicillin or IV Cephalexin or
cellulitis Streptococci (r S. ampicillin or PO amoxicillin-
aureus) amoxicillin) + IV/PO clavulanate or
cloxacillin ampicillin-
sulbactam
Necrotizing fasciitis Immediate surgical

(139) intervention essential.
1. Following Aeromonas IV fluoroquinolone + Urgent consult clinical
exposure to hydrophilia, A. IV amoxicillin- microbiologist.
freshwater; caviae; Vibrio clavulanate
seawater or vulnificus
seafood
2. Following cuts and Group A IV penicillin G + IV Add high dose IVIG (12 g/kg
abrasion; recent Streptococcus clindamycin for 1 dose) for streptococcal
chickenpox; IVDU; a
toxic shock syndrome (140)
healthy adults
3. Following intra- Polymicrobial: IV amoxicillin-

abdominal; Enterobacteriacea, clavulanate + IV
gynaecological or streptococci, fluoroquinolone
perineal surgery anaerobes
Bite wound (animal Streptococci, S. Amoxicillin- Penicillin V or x Risk of infection after cat
or human) (141) aureus, anaerobes, clavulanate or ampicillin + bite = 80%.
Pasteurella ampicillin- cloxacillin x Monotherapy with
multocida (cat), sulbactam penicillin, cloxacillin or first
Capnocytophaga generation cephalosporin
spp. (dog), inadequate.
Eikenella spp.
(human)
Central nervous
system infections
Brain abscess Usually Ceftriaxone + Cefotaxime + x Urgent consult
polymicrobial with metronidazole metronidazole neurosurgical.
aerobes and x Exclude primary focus in
anaerobes middle ear, mastoid,
paranasal sinuses, dental
and lung.
Meningitis S. suis, S. Ceftriaxone or Meropenem x If impaired cellular
(142;143) pneumoniae, N. cefotaxime immunity e.g. high dose
meningitides, steroid, add ampicillin to
group B cover Listeria spp..
Streptococcus x If rapid test (e.g. Gram
smear, antigen detection) or
other clues suggest S.
pneumoniae, add
vancomycin until sensitivity
data available. For pen-R S.
pneumoniae (MIC t2), 77%
and 5% are respectively
intermediate and resistant
to Ceftriaxone (56;144).
Intra-abdominal and
GI system infections
Secondary Enterobacteriacea, Cefuroxime + (Amoxicillin- x Surgical intervention
peritonitis (PPU, B. fragilis, other metronidazole + clavulanate or essential.
other bowel anaerobes, (gentamicin or ampicillin- x BL/BLI cover anaerobes
perforation, ruptured Enterococci netilmicin) sulbactam) + including B. fragilis.
appendicitis, (gentamicin or
diverticulitis) netilmicin)
Cholangitis, Enterobacteriacea, Amoxicillin- Ticarcillin- x Adequate biliary drainage
cholecystitis or Enterococci, clavulanate or clavulanate or essential.
other biliary sepsis Bacteroides ampicillin- (cefuroxime + x BL/BLIs covermost
sulbactam (r an metronidazole) Enterobacteriaceae,
aminoglycoside) enterococci and anaerobes.
Liver abscess Enterobacteriacea, Amoxicillin- Cefuroxime + x For all cases: serology for E.
(community-acquired) Bacteroides, clavulanate or metronidazole histolytica.
enterococci, ampicillin- x CT guided or open drainage
Entamoeba sulbactam + for large abscess.
histolytica metronidazole (for E.
histolytica)
Mild to moderate Food poisoning (B. Routine antibiotic Fluid and electrolytes
gastroenteritis cereus, S. aureus, therapy not replacement.
C. perfringens), recommended
Salmonella spp.,
E. coli,
Campylobacter
spp., Aeromonas
spp.

Moderate to severe Salmonella spp, Fluoroquinolone Fluoroquinolone resistance

gastroenteritis Campylobacter among Campylobacter
(presume bacterial)in spp. increasing. If symptoms not
persons with improving or worsening when
immunosuppresive diagnosis of campylobacter
disease (e.g. for HIV gastroenteritis is made; stop
+ve; high dose steroid fluoroquinolone and prescribe
when laboratory a course of oral macrolide for
results not available) 5-7 days.
Severe t6 unformed stool Fluoroquinolone Add metronidazole if severe

gastroenteritis /day, fever gastroenteritis after recent
(laboratory results t38.5qC; tenesmus; antibiotic therapy; replace
not available) blood or faecal fluid and electrolytes; avoid
WBC +ve antimotility agents.
Cardiovascular
infections
Subacute infective S. viridans, IV Ampicillin 2 g Obtain at least 3 sets of blood
endocarditis (CRHD, HACEK, q4h + gentamicin 1 cultures by 3 different
degenerative or Enterococci mg/kg q8h venepuncture over 24 h (label
congenital valvular “? IE” in laboratory form); then
diseases) (145;146) start IV antibiotics (147).
Acute infective S. aureus IV Cloxacillin 2 g IV Cefazolin 2 g x Usually tricuspid valve
endocarditis (IVDU) q4h + gentamicin 1 q8h infection r metastatic lung
(145;146) mg/kg q8h for the abscesses.
first 5 days x Blood culture q30min u 3
sets (label “? IE” in
laboratory form); then start
IV antibiotics immediately
(147).

Gynaecological
infections
Pelvic inflammatory N. gonorrhoeae, C. IV amoxicillin- IV Clindamycin Coverage of anaerobes
disease (or upper trachomatis, clavulanate or 600900 mg q8h important in tubo-ovarian
genital tract infection) Enterobacteriacea, cefoxitin 1-2 g q6h + gentamicin abscess, co-existing bacterial
(148) anaerobes + doxycycline vaginosis, HIV +ve (149).
Breast abscess Usually S. aureus IV/PO cloxacillin (+ Cefazolin or I & D essential; send pus for
(r anaerobes in PO metronidazole if amoxicillin- Gram smear and culture.
non-puerperal anaerobes likely) clavulanate or
abscess) ampicillin-
sulbactam
Head and neck
infections
Odontogenic or Oral anaerobes (IV Penicillin + PO Amoxicillin-
neck infection metronidazole) or clavulanate or
IV/PO clindamycin ampicillin-
sulbactam
Urinary tract
infections
Cystitis E. coli; S. PO Nitrofurantoin or PO Cephalexin or Encourage fluid intake
saprophyticus, b amoxicillin-
cotrimoxazole
group B clavulanate or
Streptococcus ampicillin-
sulbactamc
Acute Enterobacteriacea, IV Amoxicillin- (Ticarcillin- Blood culture and MSU
pyelonephritis Enterococcus, clavulanate or IV clavulanate or cultures, need to rule out
(Pseudomonas in ampicillin- piperacillin- obstructive uropathy.
catheter-related, sulbactam or PO/IV tazobactam if IV until afebrile 2448h, then
obstruction, fluoroquinolone suspect P. complete 14 days course with
transplant) aeruginosa) or oral drugs.
ceftriaxone 12g
q24h

Respiratory tract infections

Acute bacterial Respiratory IV/PO amoxicillin- Cefotaxime or a x Latest AACP/ACP-ASIM
exacerbation of viruses, S. clavulanate or new anti-Gram recommendation: antibiotic
COPD (AECB) (150- pneumoniae, H. ampicillin- positive is only indicated when all 3
152) influenzae, M. sulbactam e cardinal symptoms are
fluoroquinolone
d present: n sputum
catarrhalis for multi-
Appropriate use of resistant S. purulence, n sputum
antibiotics in AECB is pneumoniae with volume, n dyspnoea.
imperative to help penicillin MIC >2 x Penicillin-
control the emergence Pg/mL) intermediate/resistant S.
of multidrug resistant pneumoniae (MIC 0.12
organisms Pg/mL) can be treated by
high dose PO amoxicillin or
IV penicillin G (high dose
Amoxicillin-clavulanate if
co-infection by ampicillin-
resistant H. influenzae)
(152)
Acute bacterial P. aeruginosa PO Levofloxacin/ For P. aeruginosa,
exacerbation or (most) ciprofloxacin or IV fluoroquinolone should be
pneumonia in ticarcillin- given at high dose (e.g.
patient with clavulanate or Levofloxacin PO 500-750 mg
bronchiectasis piperacillin- qd; ciprofloxacin 500-750mg
tazobactam r an bd)(153;154)
aminoglycoside
Aspiration Oral anaerobes: (IV Penicillin G + PO Amoxicillin-
pneumonia Bacteroides, metronidazole) or clavulanate or
Peptostreptococci, PO clindamycin ampicillin-
Fusobacterium, S. sulbactam
milleri

Community-
acquired pneumonia
(CAP)
1. CAP, not S. pneumoniae, H. PO Amoxicillin- Meta-analysis of 127 studies
hospitalized influenzae, M. clavulanate or (n=33148): S. pneumoniae
pneumoniae, C. ampicillin- (73%); H. influenzae (14%); S.
pneumoniae, C. sulbactam r a aureus (3%); Gram-negative
psittaci (influenza macrolide rods (2%). In Hong Kong,
A, M. tuberculosis) or macrolide/azalide, tetracycline
PO amoxicillin + a or co-trimoxazole should not
newer macrolide be used alone for empiric
treatment of CAP. Locally,
5070% pen-S and pen-R S.
pneumoniae isolates (both
community and hospital
isolates) are multiply resistant
to these agents (5;155;156)
2. CAP, hospitalized As above IV/PO Amoxicillin- Cefotaxime or Modifying factors:
in general ward clavulanate or ceftriaxone r a bronchiectasis: either
(157) ampicillin- f (ticarcillin-clavulanate or
macrolides
sulbactam r a piperacillin-tazobactam or
f cefepime) + a macrolide; or
macrolides
fluoroquinolone + an
aminoglycoside
3. CAP, hospitalized As above + IV Piperacillin- Cefepime + a Ticarcillin-clavulanate and
in ICU for serious Enterobacteriaceae tazobactam or macrolide ceftazidime are not useful vs
pneumonia cefotaxime or penicillin-non-susceptible S.
ceftriaxone + a pneumoniae
macrolide

Hospital-acquired
pneumonia (HAP)
HAP, onset <4 days S. pneumoniae, H. IV/PO Ampicillin- Cefuroxime if
after admission + no influenzae, M. sulbactam or patient is
previous antibiotics catarrhalis, S. amoxicillin- penicillin-allergy
(158) aureus clavulanate (non-type I
hypersensitivity)
HAP, onset t4 days MRSA; P. IV Ticarcillin- Cefoperazone- x Refer also to guideline on
after admission + had aeruginosa, clavulanate or sulbactam or use of vancomycin.
antibiotics recently, Acinetobacter, piperacillin- cefepime r an
OR onset t5 days Klebsiella spp., tazobactam r an aminoglycoside
after admission OR Enterobacter spp. aminoglycoside
mechanical
ventilation (158)

Footnote
a
Classification and definition of group A streptococcal toxic shock syndrome (159)
Definite case = criteria IA + IIA + IIB; probable case = criteria IB + IIA + II B
Criteria IA: Isolation of group A streptococci (Streptococcus pyogenes) from a normally sterile site (e.g., blood,
cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, surgical wound).
Criteria IB: Isolation of group A streptococci (Streptococcus pyogenes) from a nonsterile site (e.g., throat, sputum,
vagina, superficial skin lesion).
Criteria IIA: Hypotension, systolic blood pressure d90 mm Hg in adults or <5th percentile for age in children, and;
Criteria IIB: t2 of the following signs:
(a) Renal impairment: creatinine t177 µmol/L for adults or >2u the upper limit of normal for age. In
patients with pre-existing renal disease, a t2-fold elevation over the baseline level.
(b) Coagulopathy: platelets d100,000/mm3 or DIC defined by prolonged clotting times, low fibrinogen
level, and the presence of fibrin degradation products.
(c) Liver involvement: alanine aminotransferase (ALT), asparate aminotransferase (AST), or total bilirubin
levels >2u the upper limit of normal for age. In patients with pre-existing liver disease a t2-fold
elevation over the baseline level.
(d) Adult respiratory distress syndrome defined by acute onset of diffuse pulmonary infiltrates and
hypoxaemia in the absence of cardiac failure, or evidence of diffuse capillary leak manifested by acute
onset of generalized oedema, or pleural or peritoneal effusions with hypoalbuminaemia.
(e) A generalized erythematous macular rash that may desquamate.
(f) Soft tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.
b
Avoid in patient with G6PD deficiency.
c
These agents preferred in patient with recent antimicrobial therapy.

d
Stratification schemes have been proposed to allow the physician to identify high risk patients for targeted
antimicrobial chemotherapy. One such scheme is as follows:
Group Criteria Pathogens

1. Acute tracheobronchitis No underlying structural disease Usually viral
2. Simple chronic bronchitis FEV1>50%, n sputum volume + H. influenzae, M. catarrhalis, S.

purulence pneumoniae
3. Complicated chronic As for group 2 + t1 of FEV1<50%, H. influenzae, M. catarrhalis, S.

bronchitis advanced age, significant co-morbidity pneumoniae
4. Chronic bronchial infection As for group 3 + continuous sputum Above + Enterobacteriaceae, P. aeruginosa
throughout year
e Caution required as unique groups of COPD patients appears to be the main reservoir of levofloxacin-resistant S.
pneumoniae (32). Suboptimal dose of levofloxacin has been associated with levofloxacin-resistant S. pneumoniae (32).
Ofloxacin and ciprofloxacin should not be used for treatment of pneumococcal infection. Levofloxacin is the L-isomer of
the racemate, ofloxacin. The MICs of most pneumococci in Hong Kong are close to the breakpoint of levofloxacin. In
patients with acute purulent exacerbation of chronic bronchitis, failures appeared to be common in those with
pneumococci (failures in 65%, 13/20) (16). The recommended dose for levofloxacin is 500 mg QD that for moxifloxacin is
400 mg QD. Opinion from clinical microbiologist suggested if use of fluoroquinolone is contemplated.
f
IV or PO erythromycin preferred. Alternatives for patients intolerant of erythromycin are clarithromycin and
azithromycin.

Guidelines on the use and choice of antibiotics in severe
acute pancreatitis
1. Criteria for severity assessment of acute pancreatitis (Table 16).
Most acute pancreatitis is mild. Severe acute pancreatitis (SAP)
occurs in about 5-13% of all patients. SAP is commonly defined as
having any of the following 4 criteria: (a) organ failure; (b) local
complication such as necrosis, pseudocyst, or abscess; (c) Ranson
score t3; or (d) at least 8 of the APACHE II criteria (160). Of all
markers available, CRP is the single most useful parameter in
predicting the severity of acute pancreatitis (161).
2. Infection risk. Pancreatic or peripancreatic infection occurs in 30-

40% patients who have >30% pancreatic necrosis in CT staging.
Infection usually occurs at least 10 days after the onset of SAP. In
patients with severe acute pancreatitis, the data suggests that
prophylactic antibiotic reduce infection and mortality (162-166).
3. Choice of antibiotics (Table 17): the agents should be able to

penetrate into pancreatic tissue. Good pancreatic tissue
concentrations have been documented for cefotaxime, piperacillin,
imipenem and metronidazole (167). In terms of activity, it seems
reasonable to provide coverage for the enteric Gram-negative bacilli
and anaerobes. Carbepenem group of antibiotic should be reserved
for the most severe form of disease (i.e. SAP with highly suspected
or documented pancreatic necrosis)
4. Duration of prophylactic antibiotics: 5 to 14 days depending on

disease severity and patient progress (162-169). Excessive and
prolonged antibiotic use in this setting is known to cause fungal
super-infection and emergence of antibiotic-resistant bacteria, and
should be avoided (170;171).
5. Work-up. Consider CT or USS guided-FNA of necrotic area for

culture if secondary pancreatic infection is suspected and if fever or
leukocytosis persist or develops beyond 7-10 days.

Table 16. Criteria for severity assessment of acute pancreatitis

Box 1. RANSON’S CRITERIA Box 2. ORGAN FAILURE
One point for each of: CVS: shock (SBP <90mmHg
At admission or mean arterial pressure
x Age > 55 yr <70mmHg or inotropic
x WBC >16,000/PL support)
x Glucose >11.1 mmol/L (>200 Resp: PaO2 <60 mmHg or
mg/dL) ventilator dependent
x LDH >350 IU/L Renal: Urea >7.4 mmol/L or
x AST >250 IU/L Creatinine >250 Pmol/L or
During initial 48 hours requiring renal replacement
x Haematocrit decrease >10% Gastrointestinal: bleeding
x BUN increase >1.8 mmol/L >500mL in 24 hours
(>5 mg/dL)
x Calcium <2 mmol/L (<8
mg/dL)
x PaO2 <60 mm Hg
x Base deficit >4 mEq/L
x Fluid sequestration >6 L

Table 17. Prophylactic use of antibiotic in acute pancreatitis
Acute pancreatitis
Severe
Mild
(Box 1 & 2)
Moderately severe Very severe

Only Ranson t3 Organ failure;
but no organ failure and CRP t150 mg/L;
CRP <150 mg/L CT proven pancreatic necrosis
Options
Options
1. Cefuroxime +
Carbapenem
metronidazole
2. Cefotaxime +
metronidazole
3. Piperacillin-
tazobactam

Management of community-acquired pneumonia

General considerations and principles
1. A number of guidelines on the management of community-

acquired pneumonia (CAP) were released or updated recently.
While these guidelines were drawn on the basis of the same set of
literature, patient stratification and specific suggestions still vary
quite a bit (157;172;173).
2. All agreed that S. pneumoniae is the most common pathogen in
CAP including those without an identifiable etiology. Hence, the
choice of agents for empirical therapy should consider the
regional data on prevalence and risk factors for drug-resistant S.
pneumoniae (DRSP).
3. Appropriate antimicrobial therapy should be initiated within 8
hours of hospitalization. Prior studies indicated that compliance
with this recommendation is associated with a significant
reduction in mortality (174).
4. Factors to be considered in choosing empirical therapy for
CAP:
(a) Place of therapy (outpatient, inpatient ward, or intensive
care unit).
(b) Role of atypical pathogens (e.g. Chlamydia pneumoniae,
Mycoplasma pneumoniae and Legionella spp.) is increasingly
being recognized. ATS guidelines even suggested that all
patients should be treated for the possibility of atypical
pathogen infections (173).
(c) Presence of modifying factors including risk factors for
DRSP (e.g. age >65 yr., beta-lactam therapy within past 3
months, alcoholism, multiple medical comorbidities,
exposure to a child in a day care centre), enteric Gram-
negatives (residence in a nursing home, underlying
cardiopulmonary disease, multiple medical comorbidities,
recent antibiotic therapy), and P. aeruginosa (e.g.
bronchiectasis).
5. Several antibiotics active against P. aeruginosa, including
cefepime, imipenem, meropenem, piperacillin, and piperacillin-
tazobactam are also highly active against DRSP. They can be
used for patients having specific risk factors for P. aeruginosa.
6. If a macrolide is relied upon for coverage of H. influenzae, the
newer macrolides (e.g. clarithromycin or azithromycin) should be
used instead of erythromycin.
7. For most patients, appropriately chosen initial antibiotic therapy
should not be changed in the first 72 h, unless there is marked
clinical deterioration.
8. Most patients with CAP will have an adequate clinical response
within 72 h. After the patient has met appropriate criteria, switch
from iv to oral therapy can be made.

Management of community-acquired pneumonia in the

era of pneumococcal resistance: conclusions from the
CDC working group
1. The current CLSI (NCCLS) categories for defining susceptibility
concentrations (i.e. penicillin G: sensitive for d0.06 Pg/mL;
intermediate for 0.1-1 Pg/mL and resistant for t2 Pg/mL) are not
clinically useful for treatment of patients with pneumococcal
pneumonia. Comparative studies of adults and children have
reported that pneumonia due to penicillin-nonsusceptible
pneumococci (most had MIC >0.1-1 Pg/mL) does not influence
the outcome of pneumonia treatment (175;176). At higher level of
resistance (penicillin MIC 2-4 Pg/mL), recent evidence suggests
that risk of mortality or suppurative complications were
increased (177;178). In one study (179), the observed increase in
mortality was confined to patients with pneumococcal isolates
with penicillin MIC of t4 Pg/mL.
2. For S. pneumoniae causing pneumonia (but not otitis media and
meningitis), the following revised categorization was suggested:
d1 Pg/mL, sensitive; 2 Pg/mL, intermediate; t4 Pg/mL resistant.
By modifying the breakpoints, it is hope that there will be
decreased use of broad-spectrum antimicrobial therapy in favour
of more narrow-spectrum therapy. Patients with pneumococcal
pneumonia caused by strains with penicillin MIC d1 Pg/mL can
be treated appropriately with optimal dosage of IV penicillin and
selected other PO/IV beta-lactams. Comparative anti-
pneumococcal activities of commonly used beta-lactams is shown
in Table 18.
3. Vancomycin is not routinely indicated for treatment of CAP or for
pneumonia caused by DRSP.
4. The CDC working group does not advocate the use of newer
fluoroquinolones for first line treatment of CAP. The reasons are:
(a) Most penicillin-nonsusceptible S. pneumoniae pneumonia
can be appropriately treated with a beta-lactam with good
anti-pneumococcal activity at optimal dosage.
(b) Concerns that resistance among pneumococci will rapidly
emerge after widespread use of this class of antibiotics.
(c) Their activity against pneumococci with high level penicillin
resistance (MIC t4 Pg/mL) makes it important that they be
reserved for selected patients with CAP.
5. Indications for use of fluoroquinolones in CAP

(a) Adults for whom one of the first line regimen has already failed.
(b) Allergic to alternative agents.
(c) Documented infection due to pneumococci with high level
penicillin resistance (penicillin MIC t4 Pg/mL).

Regional considerations for S. pneumoniae

(4;5;56;96;144;155;180-182)
1. In Hong Kong, reduced susceptibility to penicillin and resistance
to macrolides were high in both hospital (56;155) and community
settings (180;181) (50-70% and >70%, respectively).
2. Erythromycin resistant isolates are also resistant to the newer
macrolides/azalides such as clarithromycin and azithromycin
(183).
3. Globally, resistance to fluoroquinolones among the pneumococci
is low (<1-2%). Hong Kong is one of the rare exceptions in which
fluoroquinolone resistance (levofloxacin MIC t8 Pg/mL) is rapidly
emerging among the S. pneumoniae (56). The findings of two
recent multi-hospital studies were summarized below. Similar
findings have been reported from several recent international
surveillance studies (e.g. Alexander project). In local strains of S.
pneumoniae, fluoroquinolone resistance is associated with
resistance to penicillin and is a result of double mutations in
both targets (parC and gyrA) (156).
Percentage resistant to levofloxacin (MIC

t8 Pg/mL)
Year Penicillin- Penicillin- Overall Ref.
sensitive resistant
1998 0% 9.2% 5.5% (155)
2000 0% 28.4% 13.3% (56)
4. In view of the above, adherence to the CDC guidelines on the use

of the fluoroquinolones seems appropriate. Moreover,
tuberculosis is prevalent in Hong Kong and was reported to
account for ~10% of CAP in the elderly. Excess use of
fluoroquinolones in CAP may lead to: (1) delay in diagnosis of
tuberculosis; (2) increased fluororoquinolone resistance among
Mycobacterium tuberculosis (184;185). Hence, this class of
agents is not recommended as first line (or routine) therapy
in Hong Kong for CAP. In this regard, extra-care need to be
exercised in using fluoroquinolones in patients with risk factors
for fluoroquinolone-resistant S. pneumoniae (186):
x presence of COPD;

x nosocomial pneumococcal infection;
x residence in old age home; and
x past exposure to fluoroquinolones.
Ciprofloxacin and ofloxacin should not be used to treat
pneumococcal infection. Use of a suboptimal dose of
fluoroquinolone should be avoided (e.g. the dose/frequency
approved by FDA for levofloxacin in CAP is 500 mg qd). Use of
<500 mg and in divided doses should be avoided as these have
been showed to be associated with the emergence of
fluoroquinolone-resistant S. pneumoniae (156). If a respiratory
fluoroquinolone is indicated, there is evidence to suggest that the
more potent ones (e.g. gemifloxacin, moxifloxacin, gatifloxacin)
are less likely to lead to development of resistance.
5. Penicillin G (IV) or ampicillin (PO/IV) or amoxicillin (PO/IV) are
generally viewed as the beta-lactam drugs of choice for treating
infections with penicillin-susceptible and penicillin-intermediate
strains of S. pneumoniae. The following beta-lactams are not
recommended because of poor intrinsic activities against S.
pneumoniae: penicillin V, all first generation cephalosporins,
cefaclor, cefixime, ceftibuten, and loracarbef.
6. Lung infections involving strains with intermediate susceptibility
to penicillin (MIC 0.1-1 Pg/mL) may be treated with IV penicillin
G or oral amoxicillin (high dose).
7. Penicillins combined with beta-lactamase inhibitors (ampicillin-
sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam) are
active against beta-lactamase-producing organisms including H.
influenzae, M. catarrhalis, and methicillin-sensitive S. aureus.
Except in-patients with mixed infection, these drugs offer no
advantage over penicillin G or amoxicillin for the treatment of S.
pneumoniae pneumonia, including those due to penicillin-
resistant strains because beta-lactamase is not produced by S.
pneumoniae. The MIC of ampicillin, amoxicillin, piperacillin for
most local strains were similar to that of penicillin. However, the
MIC of ticarcillin is increased disproportionately among penicillin
non-susceptible strains.
8. Amoxicillin capsules taken together with standard Augmentin
(375 mg tablet) may be an acceptable alternative to high dose
Augmentin (1 g preparation) in some clinical situations. An
example of dosing for combinational use would be amoxicillin
(Amoxil) 250 mg tds + Augmentin 375 mg tds. While they are
expected to produce similar pharmacodynamic targets (T>MIC)
(187), no specific pharmacokinetic studies have been conducted
to demonstrate their bioequivalence.
Table 18. Comparative activities of commonly used beta-lactams

against Streptococcus pneumoniae with different levels of
penicillin susceptibility
Penicillin MIC
Sensitivea intermediate Resistant
d0.06 Pg/mL 0.121 Pg/mL 2 Pg/mL t4 Pg/mL
Year/type of study (ref.)
2000/hospital (56) 39.4% 11.7% 37.8% 11.1%
2000/community (181) 41.8% 32.1% 22.7% 3.4%
Agent
Penicillin V +++ +
Penicillin G +++ +++ ++ r
Ampicillin PO +++ ++ r
Ampicillin IV +++ +++ ++ r
Amoxicillin PO +++ ++ +
Piperacillin +++ ++ +
Ticarcillin ++ +
Cefotaxime +++ +++ ++ r
Ceftriaxone +++ +++ ++ r
Cefepime +++ ++ + r
Cefuroxime IV +++ ++ +
Cefuroxime PO +++ ++ r
Cefpodoxime +++ ++
Ceftazidime +++ +
Cefaclor +++
Cefixime +++
Imipenem/meropenem +++ +++ r
a interpreted according to current CLSI (NCCLS) recommendation (188).

Part V: Known pathogen therapy
Part V: Guidelines for known pathogen therapy

Guidelines for Known-Pathogen Therapy
DRUG OF CHOICE ALTERNATIVES REMARKS

Acinetobacter IV Ampicillin- Cefoperazone-sulbactam + an Sulbactam is highly active
baumannii sulbactam + an aminoglyoside (mixed infection against Acinetobacter,
aminoglyoside with P. aeruginosa) gentamicin added to prevent
Fluoroquinolone + an resistance and for synergy.
aminoglyoside (if allergic to The entry site for at least
penicillin) 50% of the Acinetobacter
bacteraemia in our hospitals
is infected intravascular
catheter. Removal of the
catheter r a short course of
antibiotic is usually
adequate treatment.
Combination therapy
recommended for all serious
infection except for
uncomplicated catheter-
related bacteraemia.
Clostridium PO metronidazole PO vancomycin (if metronidazole x Clinical efficacy:
difficile fails as documented metronidazole = PO
microbiologically) vancomycin. Relapse rate:
metronidazole = PO
vancomycin
x Metronidazole remains the
drug of choice for relapse.


Enterobacter x PO/IV x Carbapenem (for severe x Cefepime is highly active in
cloacae Levofloxacin/ infection and/or ESBL- vitro against almost all
complex ciprofloxacin for producing strain) Enterobacter isolates.
urinary tract x Emergence of AmpC
infection derepressed mutants emerge
x IV cefepime ( ± an in 20-40% of infections
aminoglycoside) treated with the second or
for severe third generation
infection cephalosporins. Use of these
agents (even in
combinations) for serious
infections (other than UTI) is
not recommended.
x One study in Hong Kong
found high prevalence of
ESBL production among E.
hormaechei (a member of the
E. cloacae complex) (21)
E coli x PO/IV ampicillin- x Cefuroxime (if resistant to
(ESBL -ve) sulbactam or amoxicillin-clavulanate), add
amoxicillin- metronidazole (if mixed
clavulanate (add infection with anaerobes likely).
an aminoglyoside x Piperacillin-tazobactam + an
if rapid aminoglyoside (if P. aeruginosa
bactericidal action or Acinetobacter are co-
desirable on pathogens)
clinical grounds)

Haemophilus x PO amoxicillin or x Fluorouinolones (if allergic to x Amoxicillin-clavulanate also

influenzae PO/IV ampicillin- penicillin) provides good coverage for
sulbactam or M. catarrhalis and S.
amoxicillin- pneumoniae.
clavulanate
Klebsiella x PO/IV ampicillin- x Cefuroxime (if resistant to x Ampicillin-sulbactam less
pneumoniae sulbactam or amoxicillin-clavulanate), add satisfactory because of poor
(ESBL -ve) amoxicillin- metronidazole (if mixed inhibitory activity of
clavulanate (add infection with anaerobes likely). sulbactam for SHV-1 beta-
an aminoglyoside x Piperacillin-tazobactam + an lactamase.
if rapid aminoglyoside (if P. aeruginosa
bactericidal action or Acinetobacter are co-
desirable on pathogens)
clinical grounds)
E. coli / K. x PO cotrimoxazole x Fluoroquinolone (add an x Carbapenem has been
pneumoniae or amoxicillin- aminoglyoside for serious shown to be effective
(ESBL +ve) clavulanate or PO infection and also if rapid clinically and is currently
nitrofurantoin or bactericidal effect is desirable the beta-lactam agent of
PO levofloxacin or clinically). choice for serious infection
ciprofloxacin for x Piperacillin-tazobactam + an by ESBL+ve E. coli /
urinary tract aminoglyoside Klebseilla spp. Data for beta-
infection lactam/beta-lactamase
x Carbapenem for inhibitor combinations
bacteraemia or limited and should be used
other serious cautiously.
infection


Pseudomonas IV Piperacillin or Cefoperazone-sulbactam + an Combination therapy
aeruginosa ticarcillin- aminoglyoside (mixed infection recommended (for
clavulanate or with Acinetobacter). synergism) for all serious
piperacilin- Levofloxacin/ciprofloxacin + an infection except for
tazobactam + an aminoglyoside (if allergic to uncomplicated catheter-
aminoglyoside penicillin). related bacteraemia.
Piperacillin-tazobactam used
instead of ceftazidime due to
rapid rise in AmpC type and
ESBL-producers in
Enterobacteriaceae.
In a parallel evaluation of
7000 P. aeruginosa isolates,
no difference was found in
the susceptibility between
piperacillin-tazobactam and
piperacillin i.e. 93.9% vs
93%

Methicilllin- PO/IV cloxacillin or x Cefazolin (if allergic to

sensitive S. amoxicillin- penicillin, but limited to those
aureus clavulanate or with minor allergy such as
ampicillin- rash alone)
sulbactam or first x Clindamycin (if allergic to
generation penicillin)
cephalosporin
Methicillin- IV vancomycin x Linezolid or teicoplanin (if x Cotrimoxazole, fusidic acid
resistant S. extensive rash, other than red- or rifampicin are useful
aureus man syndrome develop after adjuncts for deep-seated
vancomycin) infections (e.g. osteomyelitis)
but these agents should not
be administered as
monotherapy.
Stenotropho- PO/IV Cotrimoxazole + Cotrimoxazole + ticarcillin-

monas Cotrimoxazole + IV fluoroquinolone clavulanate is synergistic in
maltophilia ticarcillin- vitro. Cotrimoxazole is a key
clavulanate component in therapy.
Combination therapy
recommended for synergy
and to prevent resistance.

Streptococcus For infections x Beta-lactam/beta-lactamase x For pure pneumococcal

pneumoniaea outside the central inhibitor combination with the infection, penicillin G
nervous system: exception of cefoperazone- instead of amoxicillin-
x Penicillin- sulbactam (for mixed clavulanate is preferred,
sensitive: IV infections). switch therefore
penicillin G (4 to x Erythromycin or clindamycin recommended.
8 MU / day, q6h) (if allergic to penicillin). x >70% resistant to
x Penicillin- erythromycin. Cross-
intermediate: IV resistance to clindamycin
penicillin G (high very common.
dose, 12 to 18 x Resistance to erythromycin
MU/d; q4h)a = resistance to other newer
x Penicillin- macrolides (clarithromycin,
resistant: IV azithromycin,
cefotaxime or roxithromyxin).
ceftriaxone
a CLSI (NCCLS) MIC (Pg/mL) breakpoints for penicillin G: sensitive, d0.06; intermediate 0.12-1;
resistant t2.
These breakpoints were decided mainly for the relevance on meningitis. For pneumococcal pneumonia,
pharmacokinetic/dynamic data indicates that isolates with MIC of up to 1ï2 Pg/mL should be
considered “sensitive” to appropriate dose of penicillin, ampicillin and amoxicillin.

Part VI: Surgical prophylaxis
Part VI: Guidelines for surgical prophylaxis

General principles in surgical prophylaxis

1. Duration of prophylaxis: There is wide consensus that only a
single dose of intravenous antibiotic is needed for surgical
prophylaxis in the great majority of cases. Published evidence
showed that antibiotic prophylaxis after wound closure is
unnecessary and could lead to emergence of resistant bacteria. Most
studies comparing single- with multiple-dose prophylaxis have not
shown benefit of additional doses (189).
2. Timing: Antibiotic should be given in a sufficient dose within 30
minutes before incision. This can be facilitated by having the
anesthesiologist administer the drug in the operating room at
induction. The goal is to archieve a high antibiotic level at the time
of incision.
3. Antimicrobial dosing: The dose should be adequate based on the
patient’s body weight. An additional dose of antibiotic should be
given (intra-operatively) if the operation is still continuing after two
half-lives of the initial dose, as follows:
Suggested initial dose and time to re-dose for selected antibiotics

used for surgical prophylaxis
Antibiotic Standard Recommended
intravenous dose redosing interval (hr)
Cefazolin 12 g 25 hr
Cefuroxime 1.5 g 34
Clindamycin 600900mg 36
Amoxycillin-clavulanate 1.2 g 23
Ampicillin-sulbactam 1.5 g 23
Metronidazole 500 mg 68
Vancomycin 1 g over t 60 min 612
References for this section (189-192)

Antibiotic prophylaxis in clean operations

Type of Indications Recommended drugs
Operation
Cardiaca x Prosthetic valve x Cefazolin 1-2 g
x Coronary artery
bypass
x Pacemaker
implant
x Open-heart
surgery
Thoracica x Pulmonary x Cefazolin 1-2 g; or

resection x (Amoxicillin-
x Closed tube clavulanate 1.2 g or
thoracostomy for ampicillin-sulbactam
chest trauma 1.5 g)
Vascular x Abdominal aortic x Cefazolin 1-2 g

operations
x Prosthesis
x Groin incision
x Lower extremity
amputation for
ischaemia
Neurosurgical x Craniotomy x Cefazolin 1 g or

x V-P Shunt x Cotrimoxazole 960
mg
Orthopaedic a x Total joint Cefazolin 1-2 g

replacement (complete infusion of
x Internal fixation antibiotic before
of fractures inflation of a
tourniquet)
Ophthalmic Prevent post- x Multiple drops
operative endo- topically over 2 to 24
ophthalmitis hours gentamicin or
x Tobramycin or
x Neomycin-
gramicidin-
polymyxins and

x Cefazolin 100 mg
subconjunctivally at
the end of the
procedure
a
For hospitals or units with a high incidence of postoperative wound
infections by MRSA or MRSE, screening for MRSA may be indicated to
identify patients for additional preoperative measures such as
chlorhexidine bath, 2% mupirocin nasal ointment [Bactroban Nasal]
and/or the use of vancomycin as preoperative prophylaxis (see also
“Guidelines for prescribing vancomycin” section)(193).
b
For patients allergic to cefazolin or patients with high risk of MRSA /
MRSE infections, vancomycin 1 g infused over at least 1 h should be
given after premedication with an antihistamine. Rapid IV
administration may cause hypotension, which could be especially
dangerous during induction of anaesthesia.

Antibiotic prophylaxis in clean-contaminated operations
Type of operation Indications Recommended

drugs
Head and neck Entering oral cavity or x Cefazolin 1-2 g
pharynx x (Amoxicillin-
clavulanate 1.2 g
or ampicillin-
sulbactam 1.5 g or
clindamycin 600-
900 mg)
Ear Placement of x Gentamicin

tympanostomy tube (to eardrop
decrease incidence of
purulent otorrhoea)
Gastroduodenal High risk: x Cefazolin 1 g

x Obstruction
x Haemorrhage
x Gastric ulcer
x Malignancy
x H2 blocker
x Proton pump
inhibitor
x Morbid obesity
x Gastric bypass
x Percutaneous
endoscopic
gastrostomy
Biliary High risk: x Cefuroxime 1.5 g

x Age more than 70
years
x Acute cholecystitis
x Obstructive jaundice
x Common bile duct
stones
x Morbid obesity

Type of operation Indications Recommended

drugs
Colorectal Most procedures require Parenteral
parenteral r oral x (Cefuroxime 1.5 g
prophylaxis + metronidazole
0.5 g)
Oral
x Neomycin and
erythromycin base
1 g each P.O. tds
the day before
operation
Appendectomy Both elective and x Cefuroxime 1.5 g +

emergency procedures metronidazole 0.5
g
x Therapy should be
continued
postoperatively for
ruptured and
gangrenous
appendix
Vaginal or abdominal Both elective and x Cefazolin 1-2 g,

hysterectomy emergency procedures OR
or
x Cefuroxime 1.5 g
Urology Significant bacteriuria x Treat according to

culture result.

Antibiotic prophylaxis in contaminated-infected

operations
Type of operation Indications Recommended drugs
Ruptured viscus For treatment of x Cefuroxime 0.75 to

established infection 1.5 g q8h and
metronidazole 0.5 g
q8h
Traumatic wound For treatment of x Cefazolin 1-2 g q8h

established infection x (Ampicillin 0.5 g q6h
+ cloxacillin 0.5 g
q6h)
Bite wound For treatment of x IV/PO Amoxicillin-

established infection clavulanate or
ampicillin-sulbactam

Cost and dosage
Part VII: Cost and recommended dosage of commonly-

used antimicrobial agents

Cost and dosage
Preparation and recommended dosing regimens for antibiotics

Agents Trade name Dosage form Usual adult regimen
(generic) (unit cost, HK$) (daily dose, route,
dosing interval) a
Amikacin (129) Amikin 0.1 g vial ($18) IV 15 mg/kg q24h
0.25 g vial ($38) (750 mg q24h)b or 7.5
mg/kg q12h
0.5 g vial ($59)
Amoxicillin Amoxil 250 mg cap. ($0.14) PO 500 mg tds

125 mg/5 mL syr.
($0.13/mL)
Amoxicillin- Augmentin 0.6 g vial ($14.14) IV 1.2 g q8h

clavulanate 1.2 g vials ($28.3)
375 mg tab ($0.90) PO 375-750 mg tds
1 g tab ($ 2.49) PO 1 g bd
156 mg/5 mL syr. PO 312 mg (10 mL)
($0.46/mL) tds (syr)
457 mg/5ml “BD syr” PO 914 mg (10 mL) bd
($1.60/mL) (syr)
Ampicillin 500 mg vial ($1.98) IV 1 g q6h
250 mg cap ($0.16) PO 250500 mg qid
500 mg cap ($0.32)
125 mg/5 mL syrup
($0.20/mL)
Ampicillin- Unasyn 750 mg vial ($25) IV 1.53 g q6h

sulbactam
375 mg tab ($5.45) PO 375 mg tds
250 mg/5mL syrup
($0.93/mL)
Azithromycin Zithromax 500 mg vial ($141) IV 500 mg qd

250 mg tab ($13) PO 500 mg on first
200 mg/5ml syrup day then 250 mg q24h
($3.67/mL)
Cefazolin Cefamezin 1 g vial ($13) IV 1 g q8h
Cefepime Maxipime 1 g vial ($95.45) 12 g q12h

2 g vial ($190.91)
Cefoperazone Cefobid 2 g vial ($135) 2 g q12h

Cost and dosage

dosing interval) a
Cefoperazone+ Sulperazon 1 g vial ($89.50) 1-2 g q12h

sulbactam
Ceftazidime Fortum 1 g vial ($79.9) 1 g q8h

2 g vial ($160.8)
Cefotaxime Claforan 1 g vial ($54.6) IV 1g q68h (max 12

g/day)
Ceftriaxone Rocephin 0.25 g IM ($54) IM 250 mg once

1 g IM ($55) IM/IV 12 g/day
1 g vial IV( $31.20) q1224h (max 4
g/day)
Cefuroxime Zinacef 0.75 g vial ($8.70) IV 0.751.5 g q8h

1.5 g vial ($16.5)
Cefuroxime- Zinnat 125 mg tab ($3.8) PO 250500 mg bd

axetil
250 mg tab($7.39)
125 mg/5 mL
suspension ($1.07/mL)
Cephalexin Keflex 250 cap ($0.40) PO 250500 mg qid

500 cap ($0.68)
250mg/5mL syrup
($0.18/ml)
Ciprofloxacin Ciproxin 200 mg vial ($155) IV 200400 mg q12h

400 mg vial ($260)
250 mg tab ($1.77) PO 500750 mg bd
500 mg tab ($8.60)
Clarithromycin Klacid 500 mg vial ($50) IV 500 mg q12h

250 mg tab ($7.23) PO 250500 mg bd
500 mg tab ($14.55)
125 mg/5 mL syrup
($1.18/mL)

Cost and dosage

dosing interval) a
Clindamycin Dalacin C 150 mg/mL in 2ml vials IV 600 mg q8h (max

($17.7/mL) 2.7 g/day)
150 mg cap ($2.82) PO 150300 mg qid
300 mg cap ($5.03)
Cloxacillin 500 mg vial ($2.04) IV 0.51 g q6h (max

250 mg cap ($0.33) 12 g/day)
500 mg cap ($0.44) PO 500 mg qid
Doxycycline Vibramycin 100 mg tab ($0.25) PO 200 mg qd
Erythromycin Erythrocin 500 mg vial ($30.8) IV 500 mg q6h

250 mg tab ($0.39) PO 250500 mg qid
Flucloxacillin 125 mg/5 ml elixir PO 250500 mg qid

($0.14/mL)
Gentamicin Garamycin 20 mg/2 mL ($12) IV 3.6 mg/kg/day
(129) 80 mg/2 mL ($1.85) q24h (180 mg q24h) b
or
1.2 mg/kg/dose q8h
Imipenem Tienam 500 mg vial ($114.5) IV 500 mg q6h
Levofloxacin Cravit 500 mg vial ($248.9) IV 500 mg qd

100 mg tab ($3.81) PO 500 mg qd
250 mg ($8.6)
Linezolid Zyvox 600 mg vial ($400) IV/PO 600 mg q12h
600 mg tab ($360)
20 mg/mL syrup
($12/ml)
Meropenem 500 mg vial ($126) IV 1 g q8h
1g vial ($193.4)
Metronidazole 500 vial ($4.50) IV 500 mg q8h

200 mg tab (0.17) PO 400 mg tds
Moxifloxacin Avelox 400 mg vial ($250) IV 400 mg qd

400 mg tab ($14) PO 400 mg qd

Cost and dosage

dosing interval) a
Netilmicin Netromycin 50 mg vial ($18.5) IV 4.4 mg/kg q24h

(129) 300 mg vial ($33.6) (200 mg q24h) b or IV
2.2 mg/kg q12h
Penicillin G 1 MU vial ($2.80) IV 12 million unit

q46h (max 24 million
unit/day)
Piperacillin Pipracil 4 g vial ($56) IV 4 g q6h
Piperacillin- Tazocin 4.5 g vial ($108) IV 4.5 g q68h

tazobactam
Teicoplanin Targocid 200 mg vial ($314.6) IV 400 mg x 1 dose
then 200 mg q24h
Ticarcillin- Timentin 3.2 g vial ($52) IV 3.2 g q46h

clavulanate
Tobramycin TOBR 40 mg/mL 2 ml vial IV 3.6 mg/kg q24h
(129) suspended ($25) (180 mg q24h) b or 1.2
mg/kg q8h
Vancomycin 500 mg vial ($16.39) IV 1 g q12h or IV 500

mg q6h (i.e. 30
mg/kg/day)
PO 125 mg qid
(for refractory C.
difficile colitis)
Note: Approximate cost updated as of October 2005 in the public
service.
a Typical dosages in a 70 kg person with normal renal function. Dosage
modification may be necessary for (i) the elderly; (ii) the very obese individuals (in
whom the distribution volume of water-soluble drugs may be smaller than
expected from body mass); (iii) those with renal failure and/or IV) liver failure.
b Dosage for a typical 50 kg person given. Once daily administration of
aminoglycoside is appropriate for most infections with the possible exceptions of
neutropenic fever, infective endocarditis and in the presence of severe renal failure.

Cost and dosage
Cost comparison of selected IV antibiotics

Antibiotics Usual dosage Cost(HK$/day)
Aminoglycosides
IV Gentamicin* (3.5 mg/kg/day) 180 mg qd 5.55
IV Netilmicin* (4.4 mg/kg/day) 200 mg qd 67.2
IV Tobramycin* (3.5 mg/kg/day) 180 mg qd 56
IV Amikacin* (15 mg/kg/day) 750 mg Daily 97
Penicillins
IV Ampicillin 0.5ï1 g q6h 8ï16
IV Cloxacillin 0.5ï1 g q6h 8ï16
IV Amoxillin-clavulanate 1.2 g q8h 85
(augmentin)
IV Ampicillin-sulbactam 1.5 g q8h 150
IV Ticarcillin-clavulanate 3.2 g q6h 208
IV Piperacillin 4 g q8h 168
IV Piperacillin-tazobactam 4.5 g q8h 324
(4.5 g q6h) (432)
Cephalosporins
IV Cefuroxime 750 mg q8h 26
IV Cefazolin 1 g q8h 39
IV Ceftriaxone 1 g q12h 62
IV Cefotaxime 1 g q8h 164
IV Cefoperazone-sulbactam 1 g q12h 179
(Sulperazon) (1 g q8h) (268)
IV Cefepime 1 g q12h 191
IV Ceftazidime 1 g q8h 239
Carbapenems
IV Meropenem 0.5 g q8h 378
(1 g q8h) (580)
IV Imipenem 500 mg q6h 458

Cost and dosage
Fluoroquinolones
IV Moxifloxacin 400 mg qd 205
PO Moxifloxacin 400 mg qd 14
IV Levofloxacin 500 mg qd 249

PO Levofloxacin 500 mg qd 17
IV Ciprofloxacin 400 mg q12h 520

PO Ciprofloxacin 500 mg bd 17
Macrolides
IV Clarithromycin 500 mg q12h 100
IV Azithromycin 500 mg qd 141
Others
IV Metronidazole 500 mg q8h 14
IV Vancomycin 1 g q12h 66
IV Linezolid 600 mg q12h 800
(PO Linezolid) (600 mg q12h) (720)

service.
*Dosage for a typical 50 kg person

Cost and dosage
Cost comparison of systemic antifungal agents

Antifungal agent Usual dosage Cost
(HK$/day)
PO Itraconazole 200 mg bd 96
(capsule)
PO Itraconazole 200 mg bd 190
(solution)
IV Itraconazole 200 mg q12h 1040
PO Fluconazole 200 mg bd 249

IV Fluconazole 200 mg q12h 736
PO Voriconazole 200 mg bd 676

IV Voriconazole 200 mg q12h 1476
IV Caspofungin Loading 70 mg Day 1 2517

Maintenance 50 mg qd 1950
IV Amphotercin B (1 50 mg qd 195
mg/kg/day) *
IV Liposomal 150 mg qd 4995
amphotericin B (3
mg/kg/day) *

service.
*Dosage for a typical 50 kg person

Cost and dosage
Dosage of antimicrobial agents for CNS infections

Antibiotics* Recommended doses Cost (HK$/day)
IV Cefotaxime 2 g q4h 655
IV Ceftriaxone 2 g q12h 125
IV Cefepime 2 g q8h 573
IV Meropenem 2 g q8h 1160
IV Ampicillin 2g q4h 48
IV Penicillin G 34 MU q4h 52-69
IV Metronidazole 500 mg q6h 18

IV Vancomycin 1 g q12h 66
PO Rifampin** 600 mg qd 3
Note: * Dosage for a typical body weight t70 kg and normal renal
function.
** Rifampicin should only be used in combination with another
antibiotic for meningitis by certain bacteria (e.g. multi-
resistant Streptococcus pneumoniae or MRSA) with
documented sensitivity in susceptibility testing.

Cost and dosage
Intra-peritoneal antibiotic dosing recommendations for

patients with CAPD peritonitis
Antibiotics Intermittent dosing (once daily) *
(Add drug into 1 bag/day unless
otherwise specified) (194)
Aminoglycosides
Amikacin 2 mg/kg
Gentamicin 0.6 mg/kg
Netilmicin 0.6 mg/kg
Tobramycin 0.6 mg/kg
Cephalosporins
Cefazolin 15 mg/kg
Cefepime 1g
Cefotaxime 2g
Ceftazidime 1-1.5 g
Ceftriaxone 1g
Others
Ampicillin/sulbactam 2 g q12h
Imipenem 1 g q12h
* In patients with residual renal function, the drug dose should be

empirically increased by 25%.

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Abbreviations
Abbreviations
3GC Third generation cephalosporins

AACP American Association of Colleges of Pharmacy
ACP-ASIM American College of Physicians-
American Society of Internal Medicine
AECB Acute exacerbation of chronic bronchitis
APUA Alliance for the Prudent Use of Antibiotics
ASP Antimicrobial stewardship programme
bd Twice daily
BLBLI Beta-lactam/beta-lactamase inhibitor
CA-MRSA Community acquired methicillin resistant
Staphylococcal aureus
CAP Community acquired pneumonia
cap/caps Capsule/capsules
CDC Centers for Disease Control and Prevention
CLIS Clinical and Labortory Standards Institute
COPD Chronic obstructive pulmonary disease
CRHD Chronic rheumatic heart disease
CRKP Ceftazidime-resistant Klebsiella pneumoniae
CT Computerised tomography
D5 5% dextrose solution
DDD Defined daily dose
DRSP Drug resistant Streptococcus pneumoniae
ESBL Extended-spectrum beta lactamase
ET Empirical therapy
FDA Food and Drug Administration
FNA Fine needle aspiration
HA-MRSA Healthcare associated methicillin resistant
Staphylococcus aureu
HACEK Hemophilus parainfluenzae, H. aphropilus,
Actinobacillus, Cardiobacterium, Eikenella,

Abbreviations
Kingella
IBW Ideal body weight
IDSA Infectious Diseases Society of America
IE Infective endocarditis
IM Intramuscular
IV Intravenous
IVDA Intravenous drug abuser
KPT Known-pathogen therapy
MIC Minimal inhibitory concentration
MRPA Multiply-resistant Pseudomonas aeruginosa
MRSA Methicillin resistant Staphylococcus aureus
MSSA Methicillin sensitive Staphylococcus aureus
NCCLS National Committee for Laboratory Standards
NIH National Institues of Health
ODA Once daily aminoglycerides
PO Oral
PPU Perforated peptic ulcer
PVL Panton-Valentine leukocidin
qd Daily
qid Four times per day
syr Syrup
tab/tabs Tablet/tablets
TBW Total body weight
TDM Therapeutic drug monitoring
tds Three times per day
USS Ultrasound
VRE Vancomycin resistant Enterococcus
WHO World Health Organisation

Part I: Antibiotic resistance-local scenario 12
QUICK REFERENCE
Part II: Antimicrobial stewardship programme 21
Part III: Guidelines for selected antimicrobial use 37
Part IV: Empirical therapy of common infections 59
Part V: Known-pathogen therapy 81
Part VI: Guidelines for surgical prophylaxis 88
Part VII: Cost and dosage of antimicrobial agents 95
Soft copy of this document is available at the following web links.

http://www.hku.hk/hkucoi/impact.pdf
http://www.chp.gov.hk/files/pdf/reducing_bacterial_resistance_with_impact.pdf
http://ha.home/ho/ps/impact.pdf

IMPACT Guideline

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IMPACT Guideline

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Reducing bacterial resistance with IMPACT –

Interhospital Multi-disciplinary Programme on Antimicrobial

This guideline is available for download at:

HKU Centre of Infection

DH Centre for Health Protection

IMPACT Third Edition (Version 3.0) 1

Third Edition 2005

We seek to improve the quality of this document. If you have

IMPACT Third Edition (Version 3.0) 2

Dr. Dominic Ngai Chong, Consultant Microbiologist,

Dr. S Anandaciva Consultant

Dr. Kin Sang, CHAN Chief of Service

Dr. Wai Ming, CHAN Consultant

Dr. Sik To, LAI Consultant

Dr. Wai Man, LAI Chief of Service

Dr. Patrick CK, LI Chief of Service

Dr. Wei Kwang, LUK Senior Medical Officer

IMPACT Third Edition (Version 3.0) 3

Dr. Tak Lun, QUE Consultant Microbiologist

Dr. Loletta KY, SO Senior Medical Officer

Dr. Wing Kin, TO Senior Medical Officer

Dr. Kwan Keung, WONG Chief of Service

Dr. Sai Hung, YEUNG Consultant

Dr. Wai Chun, YIP Chief of Service

Mr. Pak Wai, LEE Chief Pharmacist

IMPACT Third Edition (Version 3.0) 4

Professor Robert MT, CHAN Professor of Infectious Diseases

Dr. Pak Leung, HO Associate Professor and Honorary

Professor Margaret IP Professor

Professor Allan R. RONALD Distinguished Professor Emeritus

Professor Kenneth WT, TSANG Professor and Honorary Consultant

Professor Kwok Yung, YUEN Chair Professor in Infectious Diseases

IMPACT Third Edition (Version 3.0) 5

Dr. Alan KL, WU Medical Officer

Dr. Tak Chiu, WU Associate Consultant

IMPACT Third Edition (Version 3.0) 6

Part I: Antibiotic resistance- local scenario ..................................12

Methicillin-resistant Staphylococcus aureus......................................16

Part II: Antimicrobial stewardship programme .............................21

Antimicrobial stewardship program: summary .................................22

Part III: Guidelines for selected antimicrobials use ......................37

Part IV: Recommendation for the empirical therapy of common

Musculoskeletal infections ...............................................................60

IMPACT Third Edition (Version 3.0) 7

Part VI: Guidelines for surgical prophylaxis..................................88

Antibiotic prophylaxis in clean operations ........................................90

Part VII: Cost and recommended dosage of commonly-used

Preparation and recommended dosing regimens for antibiotics .........96

Reference List ................................................................................105

IMPACT Third Edition (Version 3.0) 8

IMPACT Third Edition (Version 3.0) 9

IMPACT Third Edition (Version 3.0) 10

The “IMPACT” programme is a collaborative effort by recognized

The editors are grateful to the contributions by our experts in the

IMPACT Third Edition (Version 3.0) 11

Part I: Antibiotic resistance- local scenario

IMPACT Third Edition (Version 3.0) 12

Background: the problem of antimicrobial resistance in

2. Antimicrobial resistance increases drug costs, length of stay and

3. Resistance to all classes of antibiotics has developed to various

IMPACT Third Edition (Version 3.0) 13

A. baumannii 7 (2%) 9 (1%) M. catarrhalis 7 (3%) - Coagulase negative 7 (3%) 7 (2%)

B. fragilis group 9 (2%) 10 (1%) Enterobacter 9 (2%) 5 (5%) S. agalactiae 9 (2%) -

This type of MRSA is endemic in the local healthcare environment

In Hong Kong, 30-50% of all hospital S. aureus isolates are

Most HA-MRSA also encode a battery of other resistance genes, they

Antimicrobial drug resistance is now an important public health

Optimal antimicrobial use (prudent prescribing) has been defined as

There are growing concerns about antimicrobial resistance. As

In developed countries, studies have found that 30-40% of

Currently, the issue of antimicrobial resistance is complicated

The term antimicrobial stewardship is defined as the optimal

ASP involves a multidisciplinary, programmatic, prospective,

Many professional societies and public health guardians including

Most studies found this strategy effective in reducing the usage of

Measurement and monitoring is an essential part of the programme.

To allow for accurate intra- and inter-institutional comparison,

In Hong Kong, few would dispute the threat from antimicrobial

More actions are required in areas where the antimicrobial

Many studies have found that optimization of antibiotics in

ASP involves proactive monitoring and feedbacks. One alternative

Another impediment is the incorrect perception that

Considering the broader perspective, working targets are needed