Antibacterial agents act against bacterial infection either by
killing the bacterium or by arresting its growth. They do this by
targeting bacterial DNA and its associated processes, attacking
bacterial metabolic processes including protein synthesis, or
interfering with bacterial cell wall synthesis and function.

Antibacterial Agents is an essential guide to this important
class of chemotherapeutic drugs. Compounds are organised according
to their target, which helps the reader understand the mechanism of
action of these drugs and how resistance can arise. The book uses
an integrated "lab-to-clinic" approach which covers
drug discovery, source or synthesis, mode of action, mechanisms of
resistance, clinical aspects (including links to current
guidelines, significant drug interactions, cautions and
contraindications), prodrugs and future improvements.

Agents covered include:

* agents targeting DNA - quinolone, rifamycin, and nitroimidazole
antibacterial agents

* agents targeting metabolic processes - sulfonamide
antibacterial agents and trimethoprim

* agents targeting protein synthesis - aminoglycoside, macrolide
and tetracycline antibiotics, chloramphenicol, and
oxazolidinones

* agents targeting cell wall synthesis - beta-Lactam and
glycopeptide antibiotics, cycloserine, isonaizid, and
daptomycin

Antibacterial Agents will find a place on the bookshelves
of students of pharmacy, pharmacology, pharmaceutical sciences,
drug design/discovery, and medicinal chemistry, and as a bench
reference for pharmacists and pharmaceutical researchers in
academia and industry.

Professor Rosaleen Anderson, Professor of Pharmaceutical Chemistry, Sunderland Pharmacy School, University of Sunderland, UK

Professor Paul Groundwater, Professor of Medicinal Chemistry, Faculty of Pharmacy, The University of Sydney, Australia

Dr Adam Todd, Senior Lecturer in Pharmacy Practice, Sunderland Pharmacy School, University of Sunderland, UK

Dr Alan Worsley, Principal Lecturer in Pharmacy Practice, Sunderland Pharmacy School, University of Sunderland, UK

• agents targeting DNA - quinolone, rifamycin, and nitroimidazole antibacterial agents
• agents targeting metabolic processes - sulfonamide antibacterial agents and trimethoprim
• agents targeting protein synthesis - aminoglycoside, macrolide and tetracycline antibiotics, chloramphenicol, and oxazolidinones
• agents targeting cell wall synthesis - -Lactam and glycopeptide antibiotics, cycloserine, isonaizid, and daptomycin

Antibacterial Agents will find a place on the bookshelves of students of pharmacy, pharmacology, pharmaceutical sciences, drug design/discovery, and medicinal chemistry, and as a bench reference for pharmacists and pharmaceutical researchers in academia and industry.

Preface xiii

SECTION 1 INTRODUCTION TO MICROORGANISMS AND ANTIBACTERIAL CHEMOTHERAPY 1

1.1 Microorganisms 3

Key points 3

1.1.1 Classification 3

1.1.2 Structure 4

1.1.3 Antibacterial targets 6

1.1.4 Bacterial detection and identification 17

1.1.5 Other than its mode of action, what factors determine the antibacterial activity of a drug? 25

1.1.6 Bacterial resistance 27

1.1.7 The 'post-antibiotic age'? 29

References 31

Questions 33

SECTION 2 AGENTS TARGETING DNA 35

2.1 Quinolone antibacterial agents 37

Key points 37

2.1.1 Discovery 37

2.1.2 Synthesis 39

2.1.3 Bioavailability 41

2.1.4 Mode of action and selectivity 44

2.1.5 Bacterial resistance 45

2.1.6 Clinical applications 47

2.1.7 Adverse drug reactions 50

2.1.8 Drug interactions 55

2.1.9 Recent developments 56

References 60

2.2 Rifamycin antibacterial agents 63

Key points 63

2.2.1 Discovery 63

2.2.2 Synthesis 65

2.2.3 Bioavailability 68

2.2.4 Mode of action and selectivity 69

2.2.5 Bacterial resistance 71

2.2.6 Clinical applications 71

2.2.7 Adverse drug reactions 77

2.2.8 Drug interactions 78

2.2.9 Recent developments 81

References 81

2.3 Nitroimidazole antibacterial agents 85

Key points 85

2.3.1 Discovery 85

2.3.2 Synthesis 86

2.3.3 Bioavailability 86

2.3.4 Mode of action and selectivity 87

2.3.5 Mechanisms of resistance 89

2.3.6 Clinical applications 90

2.3.7 Adverse drug reactions 94

2.3.8 Drug interactions 95

2.3.9 Recent developments 96

References 97

Questions 101

SECTION 3 AGENTS TARGETING METABOLIC PROCESSES 103

3.1 Sulfonamide antibacterial agents 105

Key points 105

3.1.1 Discovery 105

3.1.2 Synthesis 107

3.1.3 Bioavailability 108

3.1.4 Mode of action and selectivity 111

3.1.5 Bacterial resistance 114

3.1.6 Clinical applications 115

3.1.7 Adverse drug reactions 119

3.1.8 Drug interactions 121

3.1.9 Recent developments 123

References 124

3.2 Trimethoprim 127

Key points 127

3.2.1 Discovery 127

3.2.2 Synthesis 128

3.2.3 Bioavailability 130

3.2.4 Mode of action and selectivity 130

3.2.5 Bacterial resistance 136

3.2.6 Clinical applications 136

3.2.7 Adverse drug reactions 138

3.2.8 Drug interactions 138

3.2.9 Recent developments 139

References 140

Questions 145

SECTION 4 AGENTS TARGETING PROTEIN SYNTHESIS 147

4.1 Aminoglycoside antibiotics 149

Key points 149

4.1.1 Discovery 149

4.1.2 Synthesis 152

4.1.3 Bioavailability 156

4.1.4 Mode of action and selectivity 158

4.1.5 Bacterial resistance 160

4.1.6 Clinical applications 161

4.1.7 Adverse drug reactions 165

4.1.8 Drug interactions 167

4.1.9 Recent developments 168

References 168

4.2 Macrolide antibiotics 173

Key points 173

4.2.1 Discovery 173

4.2.2 Synthesis 175

4.2.3 Bioavailability 177

4.2.4 Mode of action and selectivity 180

4.2.5 Bacterial resistance 181

4.2.6 Clinical applications 182

4.2.7 Adverse drug reactions 187

4.2.8 Drug interactions 189

4.2.9 Recent developments 191

References 193

4.3 Tetracycline antibiotics 197

Key points 197

4.3.1 Discovery 197

4.3.2 Synthesis 200

4.3.3 Bioavailability 205

4.3.4 Mode of action and selectivity 210

4.3.5 Bacterial resistance 213

4.3.6 Clinical applications 217

4.3.7 Adverse drug reactions 223

4.3.8 Drug interactions 224

4.3.9 Recent developments 224

References 225