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.I / ABSTRACT (CHINESE VERSION) --- p.IV / DECLARATION --- p.VI / ACKNOWLEDGEMENTS --- p.VII / TABLE OF CONTENTS --- p.IX / LIST OF TABLES --- p.XIII / LIST OF FIGURES --- p.XVI / LIST OF APPENDICES --- p.XVIII / LIST OF ABBREVIATIONS --- p.XIX / Chapter CHAPTER 1 - --- INTRODUCTION --- p.1 / Chapter 1.1 --- Antimicrobial resistance --- p.1 / Chapter 1.1.1 --- Global emergence of drug-resistant organisms --- p.1 / Chapter 1.1.2 --- Resistance problem in Hong Kong --- p.5 / Chapter 1.1.2.1 --- Antimicrobial resistance of bacterial isolates in hospital --- p.5 / Chapter 1.1.2.2 --- Antimicrobial resistance of bacterial isolates from community --- p.8 / Chapter 1.1.3 --- Dynamics of resistance --- p.11 / Chapter 1.1.4 --- Mechanisms of antimicrobial resistance --- p.12 / Chapter 1.1.4.1 --- Enzymatic inactivation or modification --- p.12 / Chapter 1.1.4.2 --- Alteration of target site --- p.13 / Chapter 1.1.4.3 --- Impaired permeability --- p.13 / Chapter 1.1.4.4 --- Efflux pumps --- p.14 / Chapter 1.1.4.5. --- Alteration of metabolic pathway --- p.14 / Chapter 1.1.5 --- Association between antimicrobial use and resistance --- p.16 / Chapter 1.1.6 --- Clinical and economic impact of resistance --- p.17 / Chapter 1.1.7 --- Measures to minimize resistance in healthcare setting --- p.19 / Chapter 1.2 --- Antimicrobial classes --- p.21 / Chapter 1.2.1 --- β-Lactams --- p.21 / Chapter 1.2.2 --- Glycopeptides --- p.23 / Chapter 1.2.3 --- Quinolones --- p.24 / Chapter 1.2.4 --- Oxazolidinones-Linezolid --- p.25 / Chapter 1.3 --- Antimicrobial Stewardship Program (ASP) --- p.26 / Chapter 1.3.1 --- Definition --- p.26 / Chapter 1.3.2 --- Strategies --- p.27 / Chapter 1.3.3 --- Multidisciplinary Antimicrobial Management Team --- p.29 / Chapter 1.3.4 --- Limitations --- p.30 / Chapter 1.3.5 --- Experience in ASP --- p.30 / Chapter 1.4 --- ASP in Hong Kong --- p.36 / Chapter 1.4.1 --- Implementation at Prince of Wales Hospital --- p.36 / Chapter 1.4.2 --- Targeted antimicrobials --- p.38 / Chapter 1.5 --- Extended-Spectrum β-Lactamases (ESBLs) --- p.40 / Chapter 1.5.1 --- Classification of β-lactamases --- p.40 / Chapter 1.5.2 --- Definition of ESBLs --- p.42 / Chapter 1.5.3 --- Types of ESBLs --- p.42 / Chapter 1.5.4 --- Epidemiology of ESBLs --- p.44 / Chapter 1.5.5 --- ESBL detection --- p.46 / Chapter 1.5.6 --- Risk factors for acquisition of ESBL-producing organisms --- p.49 / Chapter 1.5.7 --- Clinical and economic impact of infections caused by ESBL- producing organisms --- p.50 / Chapter 1.5.8 --- Treatment options for infections caused by ESBL-producing organisms --- p.51 / Chapter 1.5.8.1 --- Carbapenems --- p.52 / Chapter 1.5.8.2 --- Noncarbapenems --- p.54 / Chapter 1.5.8.2.1 --- "Quinolones, aminoglycosides and sulfonamides" --- p.54 / Chapter 1.5.8.2.2 --- Cephalosporins --- p.55 / Chapter 1.5.8.2.3 --- β-Lactam/β-lactamase inhibitor combinations --- p.56 / Chapter 1.6. --- Objectives of the study --- p.58 / Chapter CHAPTER 2 - --- METHODS --- p.60 / Chapter 2.1 --- Data collection --- p.60 / Chapter 2.2 --- ESBL detection at PWH --- p.60 / Chapter CHAPTER 3 - --- OBJECTIVE 1 --- p.62 / Chapter 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.62 / Chapter 3.2 --- Method --- p.62 / Chapter 3.2.1 --- Study setting --- p.62 / Chapter 3.2.2 --- Study design and sample --- p.62 / Chapter 3.2.3 --- Definitions --- p.63 / Chapter 3.2.4 --- Data collection --- p.64 / Chapter 3.2.5 --- Data analysis --- p.65 / Chapter 3.2.5.1 --- Outcome measures --- p.65 / Chapter 3.2.5.2 --- Statistical analysis --- p.65 / Chapter 3.3 --- Results --- p.66 / Chapter 3.3.1 --- Patient characteristics --- p.66 / Chapter 3.3.2 --- Clinical characteristics --- p.66 / Chapter 3.3.2.1 --- Source of infection --- p.66 / Chapter 3.3.2.2 --- Severity of infection-Intervention period --- p.69 / Chapter 3.3.2.3 --- Healthcare-associated infections (HAIs) --- p.69 / Chapter 3.3.3 --- Prescribing practices --- p.71 / Chapter 3.3.3.1 --- Prescriptions reviewed and pattern of antibiotic prescription --- p.71 / Chapter 3.3.3.2 --- Indication --- p.73 / Chapter 3.3.3.2.1 --- Appropriateness of indication --- p.73 / Chapter 3.3.3.2.2 --- Appropriate indications of use-Individual targeted antimicrobials --- p.75 / Chapter 3.3.3.2.3 --- Inappropriate antimicrobial use --- p.77 / Chapter 3.3.4 --- Recommendations made and acceptance --- p.79 / Chapter 3.3.5 --- Outcome measures --- p.81 / Chapter 3.3.5.1 --- Multivariate model of appropriate antimicrobial use --- p.81 / Chapter 3.3.5.2 --- Multivariate model of all-cause mortality --- p.82 / Chapter 3.3.5.3 --- Treatment outcome-intervention period --- p.85 / Chapter 3.3.6 --- Antimicrobial consumption --- p.86 / Chapter 3.3.6.1 --- Targeted antimicrobials --- p.86 / Chapter 3.3.6.2 --- Other antimicrobials --- p.86 / Chapter 3.3.7 --- Bacterial susceptibility --- p.89 / Chapter 3.3.7.1 --- Escherichia coli --- p.89 / Chapter 3.3.7.1.1 --- Resistance rates to amoxicillin/clavulanate --- p.89 / Chapter 3.3.7.1.2 --- ESBL-producing Escherichia coli --- p.89 / Chapter 3.3.7.2 --- Methicillin resistant-Staphylococcus aureus (MRSA) --- p.92 / Chapter 3.3.7.3 --- Pseudomonas aeruginosa --- p.93 / Chapter 3.3.7.3.1 --- Susceptibility rates to targeted antimicrobials --- p.93 / Chapter 3.3.7.3.2 --- Susceptibility rates to other antimicrobials --- p.93 / Chapter 3.4 --- Discussion --- p.97 / Chapter 3.4.1 --- Background characteristics of patients who were prescribed targeted antimicrobials --- p.97 / Chapter 3.4.2 --- Healthcare-associated infections (HAIs) --- p.98 / Chapter 3.4.3 --- Impact of ASP on appropriateness of antimicrobial prescription --- p.99 / Chapter 3.4.4 --- Compliance to recommendations --- p.101 / Chapter 3.4.5 --- Clinical impact of ASP --- p.101 / Chapter 3.4.6 --- Impact of ASP on antimicrobial consumptions --- p.103 / Chapter 3.4.7 --- Impact of ASP on antimicrobial resistance --- p.105 / Chapter 3.4.8 --- Influential factors associated with appropriate antimicrobial use --- p.108 / Chapter 3.4.9 --- Limitations --- p.109 / Chapter 3.4.10 --- Areas for further evaluation --- p.111 / Chapter CHAPTER 4 - --- OBJECTIVE II --- p.114 / Chapter 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.114 / Chapter 4.2 --- Method --- p.114 / Chapter 4.2.1 --- Study setting --- p.114 / Chapter 4.2.2 --- Study design and sample --- p.114 / Chapter 4.2.3 --- Definitions --- p.115 / Chapter 4.2.4 --- Data collection --- p.117 / Chapter 4.2.5 --- Data analysis --- p.118 / Chapter 4.2.5.1 --- Outcome measures: --- p.118 / Chapter 4.2.5.2 --- Statistical analysis: --- p.118 / Chapter 4.3 --- Results --- p.119 / Chapter 4.3.1 --- Patient characteristics --- p.120 / Chapter 4.3.2 --- Predisposing factors --- p.120 / Chapter 4.3.3 --- Clinical characteristics --- p.122 / Chapter 4.3.3.1 --- Type and source of infection --- p.123 / Chapter 4.3.3.2 --- Severity of illness markers --- p.123 / Chapter 4.3.4 --- Outcome measures --- p.125 / Chapter 4.3.4.1 --- Treatment outcome and reasons for therapeutic failure --- p.125 / Chapter 4.3.4.2 --- Factors associated with therapeutic failure --- p.127 / Chapter 4.3.4.2.1 --- Univariate analysis of variables to be associated with therapeutic failure --- p.127 / Chapter 4.3.4.2.2 --- Multivariate model of treatment failure --- p.129 / Chapter 4.3.4.3 --- Factors associated with all-cause mortality --- p.130 / Chapter 4.3.4.3.1 --- Univariate analysis of variables to be associated with all-cause mortality --- p.130 / Chapter 4.3.4.3.2 --- Multivariate model of all-cause mortality --- p.133 / Chapter 4.3.5 --- Subgroup analysis --- p.134 / Chapter 4.3.5.1 --- Carbapenem versus Cefoperazone/sulbactam --- p.134 / Chapter 4.3.5.2 --- Carbapenem versus Piperacillin/tazobactam --- p.141 / Chapter 4.3.5.3 --- Carbapenem versus Amoxicillin/clavulanate --- p.144 / Chapter 4.3.5.4 --- Comparison of treatment outcome --- p.147 / Chapter 4.4 --- Discussion --- p.148 / Chapter 4.4.1 --- Predisposing factors --- p.148 / Chapter 4.4.2 --- Treatment outcome --- p.149 / Chapter 4.4.3 --- Limitations and areas for further study --- p.153 / Chapter CHAPTER 5 - --- CONCLUSIONS --- p.154 / REFERENCES --- p.156 / APPENDICES --- p.169