Antimicrobial resistance and antimicrobial stewardship in a Hong Kong teaching hospital.

Thilani Indunika Udayanthi Ahangama Marasinghe.Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.Includes bibliographical references (leaves 156-168).Abstracts in English and Chinese.ABSTRACT (ENGLISH VERSION) --- p.IABSTRACT (CHINESE VERSION) --- p.IVDECLARATION --- p.VIACKNOWLEDGEMENTS --- p.VIITABLE OF CONTENTS --- p.IXLIST OF TABLES --- p.XIIILIST OF FIGURES --- p.XVILIST OF APPENDICES --- p.XVIIILIST OF ABBREVIATIONS --- p.XIXChapter CHAPTER 1 - --- INTRODUCTION --- p.1Chapter 1.1 --- Antimicrobial resistance --- p.1Chapter 1.1.1 --- Global emergence of drug-resistant organisms --- p.1Chapter 1.1.2 --- Resistance problem in Hong Kong --- p.5Chapter 1.1.2.1 --- Antimicrobial resistance of bacterial isolates in hospital --- p.5Chapter 1.1.2.2 --- Antimicrobial resistance of bacterial isolates from community --- p.8Chapter 1.1.3 --- Dynamics of resistance --- p.11Chapter 1.1.4 --- Mechanisms of antimicrobial resistance --- p.12Chapter 1.1.4.1 --- Enzymatic inactivation or modification --- p.12Chapter 1.1.4.2 --- Alteration of target site --- p.13Chapter 1.1.4.3 --- Impaired permeability --- p.13Chapter 1.1.4.4 --- Efflux pumps --- p.14Chapter 1.1.4.5. --- Alteration of metabolic pathway --- p.14Chapter 1.1.5 --- Association between antimicrobial use and resistance --- p.16Chapter 1.1.6 --- Clinical and economic impact of resistance --- p.17Chapter 1.1.7 --- Measures to minimize resistance in healthcare setting --- p.19Chapter 1.2 --- Antimicrobial classes --- p.21Chapter 1.2.1 --- β-Lactams --- p.21Chapter 1.2.2 --- Glycopeptides --- p.23Chapter 1.2.3 --- Quinolones --- p.24Chapter 1.2.4 --- Oxazolidinones-Linezolid --- p.25Chapter 1.3 --- Antimicrobial Stewardship Program (ASP) --- p.26Chapter 1.3.1 --- Definition --- p.26Chapter 1.3.2 --- Strategies --- p.27Chapter 1.3.3 --- Multidisciplinary Antimicrobial Management Team --- p.29Chapter 1.3.4 --- Limitations --- p.30Chapter 1.3.5 --- Experience in ASP --- p.30Chapter 1.4 --- ASP in Hong Kong --- p.36Chapter 1.4.1 --- Implementation at Prince of Wales Hospital --- p.36Chapter 1.4.2 --- Targeted antimicrobials --- p.38Chapter 1.5 --- Extended-Spectrum β-Lactamases (ESBLs) --- p.40Chapter 1.5.1 --- Classification of β-lactamases --- p.40Chapter 1.5.2 --- Definition of ESBLs --- p.42Chapter 1.5.3 --- Types of ESBLs --- p.42Chapter 1.5.4 --- Epidemiology of ESBLs --- p.44Chapter 1.5.5 --- ESBL detection --- p.46Chapter 1.5.6 --- Risk factors for acquisition of ESBL-producing organisms --- p.49Chapter 1.5.7 --- Clinical and economic impact of infections caused by ESBL- producing organisms --- p.50Chapter 1.5.8 --- Treatment options for infections caused by ESBL-producing organisms --- p.51Chapter 1.5.8.1 --- Carbapenems --- p.52Chapter 1.5.8.2 --- Noncarbapenems --- p.54Chapter 1.5.8.2.1 --- "Quinolones, aminoglycosides and sulfonamides" --- p.54Chapter 1.5.8.2.2 --- Cephalosporins --- p.55Chapter 1.5.8.2.3 --- β-Lactam/β-lactamase inhibitor combinations --- p.56Chapter 1.6. --- Objectives of the study --- p.58Chapter CHAPTER 2 - --- METHODS --- p.60Chapter 2.1 --- Data collection --- p.60Chapter 2.2 --- ESBL detection at PWH --- p.60Chapter CHAPTER 3 - --- OBJECTIVE 1 --- p.62Chapter 3.1 --- Title:-The impact of an Antimicrobial Stewardship Program on broad spectrum antimicrobials within a Medical Department in a Hong Kong tertiary care hospital --- p.62Chapter 3.2 --- Method --- p.62Chapter 3.2.1 --- Study setting --- p.62Chapter 3.2.2 --- Study design and sample --- p.62Chapter 3.2.3 --- Definitions --- p.63Chapter 3.2.4 --- Data collection --- p.64Chapter 3.2.5 --- Data analysis --- p.65Chapter 3.2.5.1 --- Outcome measures --- p.65Chapter 3.2.5.2 --- Statistical analysis --- p.65Chapter 3.3 --- Results --- p.66Chapter 3.3.1 --- Patient characteristics --- p.66Chapter 3.3.2 --- Clinical characteristics --- p.66Chapter 3.3.2.1 --- Source of infection --- p.66Chapter 3.3.2.2 --- Severity of infection-Intervention period --- p.69Chapter 3.3.2.3 --- Healthcare-associated infections (HAIs) --- p.69Chapter 3.3.3 --- Prescribing practices --- p.71Chapter 3.3.3.1 --- Prescriptions reviewed and pattern of antibiotic prescription --- p.71Chapter 3.3.3.2 --- Indication --- p.73Chapter 3.3.3.2.1 --- Appropriateness of indication --- p.73Chapter 3.3.3.2.2 --- Appropriate indications of use-Individual targeted antimicrobials --- p.75Chapter 3.3.3.2.3 --- Inappropriate antimicrobial use --- p.77Chapter 3.3.4 --- Recommendations made and acceptance --- p.79Chapter 3.3.5 --- Outcome measures --- p.81Chapter 3.3.5.1 --- Multivariate model of appropriate antimicrobial use --- p.81Chapter 3.3.5.2 --- Multivariate model of all-cause mortality --- p.82Chapter 3.3.5.3 --- Treatment outcome-intervention period --- p.85Chapter 3.3.6 --- Antimicrobial consumption --- p.86Chapter 3.3.6.1 --- Targeted antimicrobials --- p.86Chapter 3.3.6.2 --- Other antimicrobials --- p.86Chapter 3.3.7 --- Bacterial susceptibility --- p.89Chapter 3.3.7.1 --- Escherichia coli --- p.89Chapter 3.3.7.1.1 --- Resistance rates to amoxicillin/clavulanate --- p.89Chapter 3.3.7.1.2 --- ESBL-producing Escherichia coli --- p.89Chapter 3.3.7.2 --- Methicillin resistant-Staphylococcus aureus (MRSA) --- p.92Chapter 3.3.7.3 --- Pseudomonas aeruginosa --- p.93Chapter 3.3.7.3.1 --- Susceptibility rates to targeted antimicrobials --- p.93Chapter 3.3.7.3.2 --- Susceptibility rates to other antimicrobials --- p.93Chapter 3.4 --- Discussion --- p.97Chapter 3.4.1 --- Background characteristics of patients who were prescribed targeted antimicrobials --- p.97Chapter 3.4.2 --- Healthcare-associated infections (HAIs) --- p.98Chapter 3.4.3 --- Impact of ASP on appropriateness of antimicrobial prescription --- p.99Chapter 3.4.4 --- Compliance to recommendations --- p.101Chapter 3.4.5 --- Clinical impact of ASP --- p.101Chapter 3.4.6 --- Impact of ASP on antimicrobial consumptions --- p.103Chapter 3.4.7 --- Impact of ASP on antimicrobial resistance --- p.105Chapter 3.4.8 --- Influential factors associated with appropriate antimicrobial use --- p.108Chapter 3.4.9 --- Limitations --- p.109Chapter 3.4.10 --- Areas for further evaluation --- p.111Chapter CHAPTER 4 - --- OBJECTIVE II --- p.114Chapter 4.1 --- Title:-Treatment outcome and factors affecting treatment outcome of patients with bacteremia due to extended-spectrum β-lactamases-producing organisms receiving carbapenems or β-lactam/β-lactamase inhibitor combinations --- p.114Chapter 4.2 --- Method --- p.114Chapter 4.2.1 --- Study setting --- p.114Chapter 4.2.2 --- Study design and sample --- p.114Chapter 4.2.3 --- Definitions --- p.115Chapter 4.2.4 --- Data collection --- p.117Chapter 4.2.5 --- Data analysis --- p.118Chapter 4.2.5.1 --- Outcome measures: --- p.118Chapter 4.2.5.2 --- Statistical analysis: --- p.118Chapter 4.3 --- Results --- p.119Chapter 4.3.1 --- Patient characteristics --- p.120Chapter 4.3.2 --- Predisposing factors --- p.120Chapter 4.3.3 --- Clinical characteristics --- p.122Chapter 4.3.3.1 --- Type and source of infection --- p.123Chapter 4.3.3.2 --- Severity of illness markers --- p.123Chapter 4.3.4 --- Outcome measures --- p.125Chapter 4.3.4.1 --- Treatment outcome and reasons for therapeutic failure --- p.125Chapter 4.3.4.2 --- Factors associated with therapeutic failure --- p.127Chapter 4.3.4.2.1 --- Univariate analysis of variables to be associated with therapeutic failure --- p.127Chapter 4.3.4.2.2 --- Multivariate model of treatment failure --- p.129Chapter 4.3.4.3 --- Factors associated with all-cause mortality --- p.130Chapter 4.3.4.3.1 --- Univariate analysis of variables to be associated with all-cause mortality --- p.130Chapter 4.3.4.3.2 --- Multivariate model of all-cause mortality --- p.133Chapter 4.3.5 --- Subgroup analysis --- p.134Chapter 4.3.5.1 --- Carbapenem versus Cefoperazone/sulbactam --- p.134Chapter 4.3.5.2 --- Carbapenem versus Piperacillin/tazobactam --- p.141Chapter 4.3.5.3 --- Carbapenem versus Amoxicillin/clavulanate --- p.144Chapter 4.3.5.4 --- Comparison of treatment outcome --- p.147Chapter 4.4 --- Discussion --- p.148Chapter 4.4.1 --- Predisposing factors --- p.148Chapter 4.4.2 --- Treatment outcome --- p.149Chapter 4.4.3 --- Limitations and areas for further study --- p.153Chapter CHAPTER 5 - --- CONCLUSIONS --- p.154REFERENCES --- p.156APPENDICES --- p.16