ANTIBACTERIAL AGENTS: CHEMISTRY, MODE OF ACTION, MECHANISMS OF RESISTANCE AND CLINICAL APPLICATIONS -- Contents -- Preface -- SECTION 1: INTRODUCTION TO MICROORGANISMS AND ANTIBACTERIAL CHEMOTHERAPY -- 1.1 Microorganisms -- Key points -- 1.1.1 Classification -- 1.1.2 Structure -- 1.1.3 Antibacterial targets -- 1.1.3.1 DNA replication -- 1.1.3.2 Metabolic processes (folic acid synthesis) -- 1.1.3.3 Protein synthesis -- 1.1.3.4 Bacterial cell-wall synthesis -- 1.1.4 Bacterial detection and identification -- 1.1.5 Other than its mode of action, what factors determine the antibacterial activity of a drug? -- 1.1.5.1 Bacteriostatic or bactericidal? -- 1.1.5.2 Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) -- 1.1.5.3 Time- versus concentration-dependence -- 1.1.6 Bacterial resistance -- 1.1.7 The 'post-antibiotic age'? -- References -- Questions -- SECTION 2: AGENTS TARGETING DNA -- 2.1 Quinolone antibacterial agents -- Key points -- 2.1.1 Discovery -- 2.1.2 Synthesis -- 2.1.3 Bioavailability -- 2.1.3.1 Prodrugs -- 2.1.3.2 Bacterial uptake of quinolones -- 2.1.4 Mode of action and selectivity -- 2.1.5 Bacterial resistance -- 2.1.6 Clinical applications -- 2.1.6.1 Spectrum of activity -- 2.1.6.2 Urinary tract infections (UTIs) -- 2.1.6.3 Respiratory tract infections (RTIs) -- 2.1.6.4 Sexually transmitted infections (STIs) -- 2.1.6.5 Tuberculosis -- 2.1.6.6 Anthrax -- 2.1.6.7 Miscellaneous -- 2.1.7 Adverse drug reactions -- 2.1.7.1 Effect on QTc wave and proarrhythmic potential -- 2.1.7.2 Dermatological side effects -- 2.1.7.3 Central nervous system (CNS) effects -- 2.1.8 Drug interactions -- 2.1.8.1 Antacids -- 2.1.8.2 Theophylline -- 2.1.8.3 Digoxin -- 2.1.9 Recent developments -- References -- 2.2 Rifamycin antibacterial agents -- Key points -- 2.2.1 Discovery -- 2.2.2 Synthesis -- 2.2.3 Bioavailability.

2.2.3.1 Prodrugs -- 2.2.3.2 Bacterial uptake of rifamycins -- 2.2.4 Mode of action and selectivity -- 2.2.5 Bacterial resistance -- 2.2.6 Clinical applications -- 2.2.6.1 Tuberculosis -- 2.2.6.2 Meningitis -- 2.2.6.3 Leprosy -- 2.2.6.4 Miscellaneous -- 2.2.7 Adverse drug reactions -- 2.2.7.1 Hepatotoxicity -- 2.2.7.2 Gatrointestinal (GI) effects -- 2.2.7.3 Blood and kidney -- 2.2.7.4 Rifampicin and cholestasis treatment -- 2.2.8 Drug interactions -- 2.2.8.1 Protease inhibitors and rifampicin/rifabutin -- 2.2.8.2 Hydroxymethylglutaryl coenzyme A reducatse inhibitors and rifampicin -- 2.2.8.3 Rifampicin and warfarin -- 2.2.8.4 Rifampicin and azole antifungals -- 2.2.8.5 Rifampicin and calcium channel blockers -- 2.2.9 Recent developments -- References -- 2.3 Nitroimidazole antibacterial agents -- Key points -- 2.3.1 Discovery -- 2.3.2 Synthesis -- 2.3.3 Bioavailability -- 2.3.3.1 Bacterial uptake of metronidazole -- 2.3.4 Mode of action and selectivity -- 2.3.4.1 Selective toxicity -- 2.3.5 Mechanisms of resistance -- 2.3.6 Clinical applications -- 2.3.6.1 Spectrum of activity -- 2.3.6.2 Trichomoniasis -- 2.3.6.3 Giardiasis -- 2.3.6.4 Amoebiasis -- 2.3.6.5 Helicobacter pylori -- 2.3.6.6 Anaerobic infections -- 2.3.6.7 Rosacea -- 2.3.7 Adverse drug reactions -- 2.3.7.1 Pancreatitis -- 2.3.7.2 QT wave prolongation -- 2.3.7.3 Serotonin syndrome -- 2.3.7.4 Encephalopathy -- 2.3.8 Drug interactions -- 2.3.8.1 Alcohol -- 2.3.8.2 Warfarin -- 2.3.8.3 Phenytoin/carbamazepine -- 2.3.9 Recent developments -- References -- Questions -- SECTION 3: AGENTS TARGETING METABOLIC PROCESSES -- 3.1 Sulfonamide antibacterial agents -- Key points -- 3.1.1 Discovery -- 3.1.2 Synthesis -- 3.1.3 Bioavailability -- 3.1.3.1 Bacterial uptake of sulfonamides -- 3.1.4 Mode of action and selectivity -- 3.1.5 Bacterial resistance -- 3.1.6 Clinical applications.

3.1.6.1 Spectrum of activity -- 3.1.6.2 Protozoan infections -- 3.1.6.3 Nocardiosis -- 3.1.6.4 Burn wounds -- 3.1.6.5 Rheumatic fever -- 3.1.7 Adverse drug reactions -- 3.1.7.1 Mechanism of toxicity -- 3.1.8 Drug interactions -- 3.1.8.1 Co-trimoxazole and ACE inhibitors -- 3.1.8.2 Sulfonamides and anticoagulants -- 3.1.8.3 Sulfonamides and penicillin V -- 3.1.8.4 Sulfonamides and methotrexate -- 3.1.8.5 Sulfonamides and phenytoin -- 3.1.8.6 Sulfonamides and oral hypoglycaemic agents -- 3.1.9 Recent developments -- References -- 3.2 Trimethoprim -- Key points -- 3.2.1 Discovery -- 3.2.2 Synthesis -- 3.2.3 Bioavailability -- 3.2.3.1 Bacterial uptake of trimethoprim -- 3.2.4 Mode of action and selectivity -- 3.2.5 Bacterial resistance -- 3.2.6 Clinical applications -- 3.2.6.1 Spectrum of activity -- 3.2.6.2 Urinary tract infections (UTIs) -- 3.2.6.3 Miscellaneous -- 3.2.7 Adverse drug reactions -- 3.2.8 Drug interactions -- 3.2.8.1 Pioglitazone -- 3.2.8.2 Methotrexate -- 3.2.8.3 Lamivudine -- 3.2.8.4 Memantine -- 3.2.8.5 Digoxin -- 3.2.9 Recent developments -- References -- Questions -- SECTION 4 AGENTS TARGETING PROTEIN SYNTHESIS -- 4.1 Aminoglycoside antibiotics -- Key points -- 4.1.1 Discovery -- 4.1.2 Synthesis -- 4.1.3 Bioavailability -- 4.1.4 Mode of action and selectivity -- 4.1.5 Bacterial resistance -- 4.1.6 Clinical applications -- 4.1.6.1 Spectrum of activity -- 4.1.6.2 Infective endocarditis -- 4.1.6.3 Listeria meningitis -- 4.1.6.4 Chronic pulmonary infection in cystic fibrosis -- 4.1.6.5 Miscellaneous -- 4.1.7 Adverse drug reactions -- 4.1.7.1 Ototoxicity -- 4.1.7.2 Nephrotoxicity -- 4.1.7.3 Dosing schedule -- 4.1.8 Drug interactions -- 4.1.8.1 Gentamicin and furosemide -- 4.1.8.2 Aminoglycoside antibiotics and β-lactams -- 4.1.8.3 Aminoglycosides and NSAIDs -- 4.1.8.4 Aminoglycosides and general anaesthetics (volatile).

4.1.8.5 Aminoglycosides and neuromuscular blocking agents -- 4.1.9 Recent developments -- References -- 4.2 Macrolide antibiotics -- Key points -- 4.2.1 Discovery -- 4.2.2 Synthesis -- 4.2.3 Bioavailability -- 4.2.4 Mode of action and selectivity -- 4.2.5 Bacterial resistance -- 4.2.6 Clinical applications -- 4.2.6.1 Spectrum of activity -- 4.2.6.2 Donovanosis -- 4.2.6.3 Community-acquired pneumonia -- 4.2.6.4 Eradication of Helicobacter pylori -- 4.2.6.5 Pertussis -- 4.2.6.6 Miscellaneous -- 4.2.7 Adverse drug reactions -- 4.2.7.1 Effects upon GI motility -- 4.2.7.2 Pro-arrhythmic potential -- 4.2.7.3 Skin rash -- 4.2.7.4 Hearing loss -- 4.2.8 Drug interactions -- 4.2.8.1 Macrolide drug interactions -- 4.2.9 Recent developments -- References -- 4.3 Tetracycline antibiotics -- Key points -- 4.3.1 Discovery -- 4.3.2 Synthesis -- 4.3.2.1 Biosynthesis of tetracyclines -- 4.3.2.2 Chemical synthesis of tetracyclines -- 4.3.3 Bioavailability -- 4.3.4 Mode of action and selectivity -- 4.3.5 Bacterial resistance -- 4.3.5.1 Efflux pumps -- 4.3.5.2 Ribosomal protection proteins -- 4.3.5.3 Enzymatic degradation of tetracyclines -- 4.3.5.4 Glycylcyclines -- 4.3.6 Clinical applications -- 4.3.6.1 Spectrum of activity -- 4.3.6.2 Acne vulgaris and rosacea -- 4.3.6.3 Syphilis -- 4.3.6.4 Chlamydia -- 4.3.6.5 Lyme disease -- 4.3.6.6 Miscellaneous -- 4.3.7 Adverse drug reactions -- 4.3.7.1 Hepatotoxicity -- 4.3.7.2 Fanconi syndrome -- 4.3.8 Drug interactions -- 4.3.9 Recent developments -- References -- 4.4 Chloramphenicol -- Key points -- 4.4.1 Discovery -- 4.4.2 Synthesis -- 4.4.3 Bioavailability -- 4.4.4 Mode of action and selectivity -- 4.4.5 Bacterial resistance -- 4.4.6 Clinical applications -- 4.4.6.1 Spectrum of activity -- 4.4.6.2 Eye infections -- 4.4.6.3 Miscellaneous -- 4.4.7 Adverse drug reactions -- 4.4.8 Drug interactions -- 4.4.9 Recent developments.

References -- 4.5 Oxazolidinones -- Key points -- 4.5.1 Discovery -- 4.5.2 Synthesis -- 4.5.3 Bioavailability -- 4.5.4 Mode of action and selectivity -- 4.5.5 Bacterial resistance -- 4.5.6 Clinical applications -- 4.5.6.1 Spectrum of activity -- 4.5.6.2 Complicated skin and soft-tissue infections (cSSTIs) -- 4.5.6.3 Community-acquired pneumonia and hospital-acquired pneumonia -- 4.5.7 Adverse drug reactions -- 4.5.8 Drug interactions -- 4.5.9 Recent developments -- References -- Questions -- SECTION 5 AGENTS TARGETING CELL-WALL SYNTHESIS -- 5.1 β-Lactam antibiotics -- Key points -- 5.1.1 Discovery -- 5.1.1.1 Structure elucidation -- 5.1.1.2 Cephalosporins -- 5.1.1.3 Carbapenems -- 5.1.1.4 Monobactams -- 5.1.2 Synthesis -- 5.1.2.1 Penicillins -- 5.1.2.2 Cephalosporins -- 5.1.2.3 Carbapenems -- 5.1.2.4 Monobactams -- 5.1.3 Bioavailability -- 5.1.3.1 Bacterial uptake of β-lactams -- 5.1.4 Mode of action and selectivity -- 5.1.5 Bacterial resistance -- 5.1.5.1 β-Lactamases -- 5.1.6 Clinical applications -- 5.1.6.1 Spectrum of activity -- 5.1.6.2 Uncomplicated skin and soft-tissue infections -- 5.1.6.3 Osteomyelitis -- 5.1.6.4 Pneumonia -- 5.1.6.5 Miscellaneous -- 5.1.7 Adverse drug reactions -- 5.1.7.1 Mechanism of hypersensitivity -- 5.1.7.2 Clinical features of β-lactam hypersensitivity -- 5.1.8 Drug interactions -- 5.1.8.1 β-Lactams and combined oral contraceptives -- 5.1.8.2 Methotrexate and penicillins -- 5.1.8.3 Warfarin and β-lactams -- 5.1.9 Recent developments -- References -- 5.2 Glycopeptide antibiotics -- Key points -- 5.2.1 Discovery -- 5.2.2 Synthesis -- 5.2.3 Bioavailability -- 5.2.4 Mode of action and selectivity -- 5.2.5 Bacterial resistance -- 5.2.6 Clinical applications -- 5.2.6.1 Spectrum of activity -- 5.2.6.2 Clostridium difficile infection -- 5.2.6.3 Serious Gram positive infections resistant to other antibiotics.

5.2.7 Adverse drug reactions.