Antimicrobial Resistance and Implications for the 21st Century (eBook)

Preface 6
Contents 7
Mechanisms of Resistance by Gram-Positive Bacteria ( Streptococci and Enterococci) 12
1.1 Streptococcus Pneumoniae Resistance to Penicillin: Mechanism and Clinical Significance 12
1.1.1 Microbiologic Characteristics of S. pneumoniae 12
1.1.2 Historical Overview of Pneumococcal Antibiotic Resistance 13
1.1.3 Clinical and Microbiological Concepts of Antibiotic Resistance 14
1.1.4 Overview of Bacterial Resistance 15
1.1.5 Mechanisms of Resistance to Penicillin and Cephalosporins 16
1.1.6 Relationship Between Pneumococcal Serotypes and Penicillin- Resistance 19
1.1.7 Risk Factors for Infection by Penicillin-Resistant S. pneumoniae 19
1.1.8 The Clinical Consequences of Penicillin Resistance in Patients with Pneumonia 20
1.1.9 Combination Antimicrobial Therapy for Pneumococcal Pneumonia 24
1.2 Streptococcal Resistance to Macrolides, Tetracycline, Quinolones, and Clindamycin— Mechanisms and Implications 25
1.2.1 Macrolides and Related Antimicrobial Agents 25
1.2.2 Quinolones 28
1.2.3 Mechanisms of Resistance to Other Antimicrobials 34
1.2.4 Multidrug-Resistant S. pneumoniae 34
1.3 Streptococcal and Enterococcal Resistance to Streptogramin, Oxazolidinones, Vancomycin— Emerging Issues 35
1.3.1 Glycopeptides: Vancomycin 36
1.3.2 Lipopeptides: Daptomycin 39
1.3.3 Oxazolidinones: Linezolid 40
1.3.4 Streptogramins: Quinupristin–Dalfopristin 41
1.4 Future Directions 43
References 45
Emergence of MRSA in the Community 58
2.1 Introduction 58
2.2 Epidemiology and Mechanisms of Resistance in MRSA in the Community 59
2.2.1 Epidemiology and Clinical Presentation of MRSA 59
2.2.2 Transmission of CA-MRSA 62
2.2.3 Microbiology and Mechanisms of Resistance 67
2.3 Considerations in Management of S. aureus Infection in the Community 71
2.3.1 Management of Severe or Invasive MRSA Infections 72
2.3.2 Management of MRSA Skin or Soft Tissue Infections 72
2.3.3 Strategies to Eliminate S. aureus Colonization 75
2.4 Prevention of MRSA in the Community 76
2.4.1 Public Health Officials 76
2.4.2 Medical Providers and Infection Control Practitioners 76
2.4.3 Patients and Members of the Community 77
2.5 Future Directions 78
References 79
Antimicrobial Resistance to Sexually Transmitted Infections 87
3.1 Introduction 87
3.2 Genital Herpes 87
3.3 Trichomonas vaginalis 89
3.4 Syphilis 90
3.5 Chlamydia 91
3.6 Gonorrhea 92
3.6.1 Mechanisms of Resistance 95
3.7 Haemophilus ducreyi (Chancroid) 98
References 100
Resistance of Gram-Negative Bacilli to Antimicrobials 107
4.1 Background and Epidemiology of the Emerging Problem WorldWide with Multiresistant Gram- Negative Bacilli 107
4.2 Mechanisms of Resistance 108
4.2.1 New ß-Lactamases 108
4.2.2 Quinolones 116
4.2.3 Resistance to Aminoglycosides 127
4.2.4 Resistance to Tetracyclines 134
4.2.5 Efflux Mediated Resistance 137
4.3 Future Directions 143
4.3.1 Preventive Measures 143
4.3.2 New Agents 145
4.4 Concluding Remarks 146
References 146
Mycobacterial Antimicrobial Resistance 170
5.1 Definitions and Causation 170
5.2 Global Epidemiology of Tuberculosis 170
5.2.1 Principal Conclusions of Report 171
5.2.2 Asia 172
5.2.3 Africa 177
5.2.4 The Americas 178
5.2.5 Europe 179
5.3 The Bacterium 181
5.3.1 Mycobacterium tuberculosis Complex 182
5.3.2 Environmental Mycobacteria 183
5.3.3 Mycobacterium leprae 183
5.4 Mechanisms of Development of Drug Resistance 184
5.4.1 Introduction 184
5.4.2 Rifampicin Resistance 184
5.4.3 Isoniazid Resistance 185
5.4.4 Other Drug-Resistant Mechanisms 186
5.5 Laboratory Diagnosis 186
5.5.1 Culture on Solid Media 187
5.5.2 Automated Liquid-Based Culture 187
5.5.3 Phenotypic Methods 188
5.5.4 Molecular Methods 189
5.6 The Development of Drug Resistant Tuberculosis 190
5.7 Clinical Presentation of Drug-Resistant Tuberculosis 191
5.8 AIDS in the Presentation of MDR-TB 191
5.9 HIV and TB 191
5.10 MDR-TB Outbreaks 192
5.11 The Treatment of Multidrug Resistant Tuberculosis 192
5.11.1 Introduction 192
5.11.2 Management of Non-MDR Resistance 194
5.11.3 Multi-drug-Resistant Tuberculosis 194
5.11.4 Outcomes in the Treatment of MDR-TB: The Place of Directly Observed Therapy ( DOT) 198
5.11.5 Outcomes in Children 198
5.12 New Drugs in the Management of MDR-TB 199
5.13 Immunotherapy of Multidrug Resistant Pulmonary Tuberculosis 199
5.14 Summary of Management Plan of Multidrug Resistant Pulmonary Tuberculosis 200
5.15 Therapeutic Drug Monitoring in Anti-tuberculosis Chemotherapy 200
5.16 Environmental (Atypical) Mycobacteria 201
5.16.1 Introduction 201
5.16.2 Bacteriology and Pathology 202
5.16.3 Clinical Presentation 203
5.16.4 Chest Radiography and Diagnosis 203
5.16.5 Disseminated Disease 204
5.16.6 Clarithromycin and MAC in HIV Infection 205
References 206
Antimicrobial Resistance of Anaerobic Bacteria 215
6.1 Introduction 215
6.2 Anaerobic Antimicrobial Susceptibility Testing (AST) 216
6.2.1 Methods 216
6.3 Antimicrobial Resistance among Anaerobes 221
6.3.1 Future Directions of Research 222
6.3.2 Mechanisms and Prevalence of Resistance 222
6.3.3 Antibiotic Resistance by Genus and Species 222
6.3.4 Resistance to ß-Lactam Antibiotics 226
6.3.5 Conclusion 232
References 232
Clinical Significance and Biological Basis of HIV Drug Resistance 238
7.1 Introduction 238
7.2 Generation of HIV-1 Drug Resistance 241
7.3 Inhibitors of Reverse Transcriptase 241
7.4 Protease Inhibitors 244
7.5 Entry Inhibitors 246
7.6 Antiretroviral Drug Resistance in Non-B Subtypes of HIV- 1 Group M 247
7.7 Transmission of HIV Drug-Resistance 248
7.8 Clinical Value of HIV Drug Resistance Testing 251
7.9 Future Direction 253
7.10 Conclusion 254
References 255
Resistance of Herpesviruses to Antiviral Agents 269
8.1 Antiviral Agents for Herpesvirus Infections 269
8.2 Human Cytomegalovirus Resistance 271
8.2.1 Phenotypic and Genotypic Assays to Evaluate HCMV Drug Susceptibility 271
8.2.2 Clinical Significance, Incidence and Risk Factors for Drug- Resistant HCMV Infections 273
8.2.3 Role of HCMV UL97 and UL54 Mutations in Drug-Resistant Clinical Strains 276
8.2.4 Management of Infections Caused by Resistant HCMV Strains 278
8.3 Herpes Simplex Virus and Varicella-Zoster Virus Resistance 279
8.3.1 Phenotypic and Genotypic Assays to Evaluate HSV and VZV Drug Susceptibility 279
8.3.2 Clinical Significance, Incidence, and Risk Factors for Drug- Resistant HSV and VZV Infections 281
8.3.3 Role of Viral TK and DNA Polymerase Mutations in Drug- Resistant Clinical Strains 282
8.3.4 Management of Infections Caused by Resistant HSV and VZV Strains 283
8.4 Conclusions and Future Directions 285
References 286
Hepatitis Virus Resistance 297
9.1 Introduction 297
9.2 Hepatitis B Virus Resistance 297
9.2.1 HBV Virological Characteristics 298
9.2.2 Current Treatment of Chronic HBV Infection 299
9.2.3 HBV Resistance to Specific Inhibitors 300
9.2.4 Assessment of HBV Resistance 305
9.2.5 Prevention of HBV Resistance 307
9.2.6 Management of HBV Resistance 309
9.3 Hepatitis C Virus Resistance 310
9.3.1 HCV Virological Characteristics 310
9.3.2 Current Treatment of Chronic HCV Infection 311
9.3.3 HCV Resistance to Interferon alpha-Ribavirin Therapy 312
9.3.4 HCV Resistance to Specific HCV Inhibitors 315
9.3.5 Prevention of HCV Resistance to Specific HCV Inhibitors 318
9.3.6 Management of HCV Treatment Failure 318
9.4 Conclusion 319
References 319
Resistance to Antifungal Agents 330
10.1 Introduction 330
10.1.1 Incidence of Fungal Infections 330
10.1.2 Microbiological Resistance Versus Clinical Resistance 331
10.2 Mechanisms of Resistance 331
10.2.1 Antifungal Drugs 331
10.2.2 Polyenes 331
10.2.3 Flucytosine (5-FC) 336
10.2.4 Ergosterol Biosynthesis Inhibitors 337
10.2.5 Allylamines 344
10.2.6 ß-1,3 Glucan synthesis inhibitors 346
10.3 Clinical Implications 348
10.3.1 Detecting In Vitro Resistance 348
10.3.2 MIC Interpretation 349
10.3.3 Limitations of In Vitro Susceptibility Tests 350
10.4 Antifungal Prophylaxis: A Breeding Ground For Resistance? 352
10.4.1 Vulvovaginal Candidiasis 353
10.4.2 Invasive Fungal Infection 353
10.5 Future Considerations and Newer Agents 356
10.5.1 Echinocandins 356
10.5.2 Combination Therapy 356
10.5.3 Cispentacin 357
10.5.4 Sordarins 357
10.6 Conclusions 357
References 358
An Anti-mutant Approach for Antimicrobial Use 375
11.1 Introduction 375
11.2 Loss of Antimicrobial Susceptibility 376
11.3 Overview of Strategies for Limiting Antimicrobial Resistance 377
11.4 Mutant Selection Window 379
11.4.1 Definition of the Selection Window 379
11.4.2 Selection Window with Eukaryotic Pathogens 381
11.4.3 Complex Situations 383
11.4.4 Estimating MPC 384
11.4.5 Estimating MPC from MIC? 385
11.5 Experimental Support for the Selection Window Hypothesis 386
11.5.1 In Vitro Dynamic Models 386
11.5.2 Animal Models 388
11.5.3 Clinical Study 389
11.6 Pharmacokinetic/Pharmacodynamic Indices and MPC 390
11.7 Stepwise Accumulation of Resistance Mutations 390
11.8 Clinical Implications of the Mutant Selection Window Hypothesis 392
11.9 Assumptions and Limitations of the SelectionWindow 394
11.10 Concluding Remarks 395
References 396
Index 405