Antibiotics: Containing the Beta-Lactam Structure Part II

ISBN-13: 9783642689031 / Angielski / Miękka / 2011 / 479 str.

P. Actor;M.C. Browning;N.H. Georgopapadakou

Opis

It is quite amazing that the oldest group of medically useful antibiotics, the fJ-Iactams, are still providing basic microbiologists, biochemists, and clinicians with surprises over 50 years after Fleming's discovery of penicillin production by Penicillium. By the end of the 1950s, the future of the penicillins seemed doubtful as resistant strains of Staphylococcus aureus began to increase in hospital populations. However, the development of semisynthetic penicillins provided new structures with resistance to penicillinase and with broad-spectrum activity. In the 1960s, the discovery of cephalosporin C production by Cephalosporium and its conversion to valuable broad-spectrum antibiotics by semisynthetic means excited the world of chemotherapy. In the early 1970s, the 40-year-old notion that fJ-Iactams were produced only by fungi was destroyed by the discovery of cephamycin production by Streptomyces. Again this basic discovery was exploited by the deVelopment of the semisynthetic cefoxitin, which has even broader activity than earlier fJ-Iactams. Later in the 1970s came the discoveries of nocardicins from Nocardia, clavulanic acid from Streptomyces, and the carbapenems from Streptomyces. Now in the 1980s we learn that fJ-Iactams are produced even by unicellular bacteria and that semisynthetic derivatives of these monobactams may find their way into medicine. Indeed, the future of the prolific fJ-Iactam family seems brighter with each passing decade.

Spis treści

12 Bacterial Enzymes Interacting with ?-Lactam Antibiotics.- A. Introduction.- I. Classification of ?-Lactam Antibiotics.- II. Mode of Action of ?-Lactam Antibiotics.- 1. Structure and Synthesis of Peptidoglycan.- 2. The Tipper and Strominger Hypothesis for Penicillin Action.- III. Classification of Enzymes Interacting with ?-Lactam Antibiotics.- 1. Enzymes Acting on Peptidoglycan.- 2. Enzymes Degrading ?-Lactam Antibiotics.- B. Bacterial Proteins Binding ?-Lactam Antibiotics.- I. General.- II. Penicillin-Binding Proteins in Gram-Negative Bacteria.- 1. Escherichia coli.- 2. Other Enterobacteria.- 3. Pseudomonads.- 4. Other Bacteria.- III. Penicillin-Binding Proteins in Gram-Positive Bacteria.- 1. Bacilli.- 2. Micrococci.- 3. Streptococci.- 4. Actinomycetes.- C. Enzymes Inhibited by ?-Lactam Antibiotics.- I. dd-Carboxypeptidases.- 1. dd-Carboxypeptidases in Gram-Negative Bacteria.- 2. dd-Carboxypeptidases in Gram-Positive Bacteria.- II. Peptidoglycan Transpeptidase.- D. ?-Lactamases.- I. General.- II. ?-Lactamases in Gram-Positive Bacteria.- 1. Staphylococci.- 2. Bacilli.- 3. Streptomycetes.- 4. Other Actinomycetes.- III. ?-Lactamases in Gram-Negative Bacteria.- 1. Anaerobic.- 2. Aerobic.- E. Interaction with the ?-Lactam Nucleus.- I. Components of the Interaction.- 1. Kinetic Parameters.- 2. Conformational Changes.- 3. Nature of the Covalent Complex.- 4. Nature of Release Products.- II. Streptomyces R61 dd-Carboxypeptidase.- III. ?-Lactamases and ?-Lactam Inhibitors.- 1. Clavulanic Acid.- 2. Penicillin Sulfones.- 3. Halopenicillanic Acids.- 4. Carbapenems.- F. Concluding Remarks.- References.- 13 In Vitro and In Vivo Laboratory Evaluation of ?-Lactam Antibiotics.- A. Historical.- I. Penicillins.- II. Cephalosporins.- III. Cephamycins (7-?-Methoxy Cephalosporins).- IV. ?-Lactams of Novel Structure.- B. ?-Lactam Laboratory Evaluation Procedures.- I. Introduction.- II. In Vitro Test Procedures.- 1. Spectrum of Activity and Sensitivity Tests.- 2. Speed of Action Test.- 3. Susceptibility Disc Test.- 4. Interaction and Synergy Tests.- 5. Effect on Morphology.- 6. Procedures Using Anaerobes.- 7. Factors Influencing In Vitro Tests.- 8. Enzymes and Resistance to ?-Lactam Antibiotics.- 9. Automation and Miniaturization.- 10. In Vitro Models to Simulate In Vivo Conditions.- III. In Vivo Test Procedures.- 1. Mouse Protection Test.- 2. Specialized Test Procedures.- 3. Tests Using Anaerobes.- IV. In Vitro-In Vivo Relationships.- C. Representative ?-Lactam Agents.- References.- 14 ?-Lactam Antibiotics: Structure-Activity Relationships.- A. Introduction: Scope.- I. Structure.- II. Activity.- B. Clinically Useful Penicillins.- I. Natural, Biosynthetic, and Related Penicillins.- II. Penicillinase-Resistant Penicillins.- III. Broad-Spectrum Penicillins.- 1. ?-Aminopenicillins.- 2. ?-Carboxy and ?-Sulfopenicillins.- 3. Acylampicillins.- 4. 6-Acylamino Alternatives: Quaternary Heterocyclic Aminopenicillanic Acids and 6-Amidinopenicillanic Acids.- 5. A 6?-Methoxy Penicillin (Temocillin).- C. Clinically Useful Cephalosporins.- I. Basic Structure-Activity Relationships.- II. ?-Lactamase-Sensitive Cephalosporins.- 1. 7?-Acylamino Group Modifications.- 2. Metabolic Stability.- 3. 3-Substituent Modifications.- III. Cephalosporins with Special Pharmacokinetic Properties.- 1. Cephalosporins with High and Prolonged Serum Levels.- 2. Cephalosporins Absorbed Orally.- IV. ?-Lactamase-Resistant Cephalosporins.- 1. Cephalosporins with Moderate ?-Lactamase Resistance.- 2. Cephamycins.- 3. Cephalosporins with Significant ?-Lactamase Resistance.- V. Oxacephalosporins.- D. Nonclassic ?-Lactams.- I. Penems and Carbapenems.- 1. Carbapenems: Thienamycins, Olivanic Acids, and Related Structures.- 2. Penems.- 3. Oxapenems.- II. Monocyclic ?-Lactams.- 1. Nocardicins.- 2. Monobactams.- III. ?-Lactamase Inhibitors.- 1. Penicillins and Cephalosporins as Inhibitors.- 2. Progressive ?-Lactamase Inhibitors.- E. Other Structure-Activity Relationships.- References.- 15 Pharmacokinetics of ?-Lactam Antibiotics.- A. Introduction.- B. Penicillins.- I. Benzylpenicillin (Penicillin G).- II. Phenoxyalkylpenicillins.- 1. Phenoxymethylpenicillin (Penicillin V).- 2. Pheneticillin.- 3. Propicillin.- 4. Phenbenicillin.- III. Clometocillin.- IV. Methicillin.- V. Ancillin.- VI. Nafcillin.- VII. Isoxazolylpenicillins.- 1. Oxacillin.- 2. Cloxacillin.- 3. Dicloxacillin.- 4. Flucloxacillin.- VIII. Ampicillin.- 1. Hetacillin.- 2. Pivampicillin.- 3. Bacampicillin.- 4. Talampicillin.- 5. Metampicillin.- 6. Methoxymethyl Ester of Hetacillin.- IX. Amoxicillin.- X. Azidocillin.- XI. Epicillin.- XII. Cyclacillin.- XIII. Carbenicillin.- 1. Carindacillin.- 2. Carfecillin.- XIV. Ticarcillin.- XV. Sulbenicillin.- XVI. Ureidopenicillins.- 1. Azlocillin.- 2. Mezlocillin.- 3. Piperacillin.- 4. Bay k 4999.- 5. BL-P1654.- C. Cephalosporins.- I. Cephalosporanic Acids.- 1. Cephalothin.- 2. Cephapirin.- 3. Cefotaxime.- 4. Cephaloglycine.- 5. Cephacetrile.- II. Desacetoxycephalosporanic Acids.- 1. Cephalexin.- 2. Cephradine.- 3. Cefadroxil.- 4. FR-10612.- 5. HR-580.- 6. RMI 19,592.- III. 3-(5-Methyl-1,3,4-thiadiazol-2-ylthiomethyl)ceph-3-em-4-oic Acids.- 1. Cefazolin.- 2. Cephanone.- 3. Cefazedone.- 4. Ceftezole.- IV. 3-(1-Pyridylmethyl)-ceph-3-em-4-oic Acids.- 1. Cephaloridine.- 2. Cefsulodin (CGP 7174/E, SCE-129).- 3. GR20263.- V. 3-{[(1-Methyl-1H-tetrazol-5-yl)thio]methyl}-ceph-3-em-4-oic Acids.- 1. Cefamandole Nafate.- 2. Ceforanide.- 3. Cefazaflur.- 4. Cefoperazone.- 5. Cefonicid (SKF-75073).- VI. Derivatives of 3-Desacetoxymethylcephalosporanic Acid.- 1. Cefroxadine.- 2. Cefaclor.- 3. Cefatrizine.- VII. Cefuroxime.- VIII. Ceftizoxime.- IX. Ro 13-9904.- X. Cephamycins.- 1. Cefoxitin.- 2. Cefmetazole (CS-1170).- D. Other ?-Lactam Antibiotics.- I. Moxalactam (LY 127935).- II. Clavulanic Acid.- III. Mecillinam.- References.- 16 Toxicology of ?-Lactam Antibiotics.- A. Introduction.- B. Local Reactions to Parenteral Administration.- C. Gastrointestinal Side Effects.- I. Nonspecific Diarrhea.- II. Pseudomembranous Colitis.- III. Ischemic Colitis.- D. Immunologically Mediated Toxicity.- I. Human Toxicity.- II. Sensitization Process.- E Immune Hemolytic Anemia.- F. Neutropenia.- G. Disorders of Hemostasis.- I. Thrombesthenia.- II. Plasma Factor Coagulopathy.- III. Thrombocytopenia.- H. Interstitial Nephritis and Cystitis.- I. Clinical Picture.- II Immunofluorescence.- III. Cystitis.- I. Nephrotoxicity.- I. Human Toxicity.- II. Cellular Mechanisms.- 1. Uptake.- 2. Efflux: Cephaloridine.- 3. Reactivity or Receptor Affinity: Cephaloglycin.- III. Less Toxic Cephalosporins.- 1. Additive Aminoglycoside-Cephalosporin Toxicity.- 2. Effects of Ureteral Obstruction.- IV. Molecular Basis of Toxicity.- 1. Metabolite Hypothesis.- 2. Mitochondrial Respiratory Toxicity.- J. Hepatic Toxicity.- K. Neurotoxicity.- I. Human Toxicity.- II. Animal Toxicity.- III. Mechanism.- 1. Effects on Gamma-Aminobutyric Acid (GABA)-Mediated Transmission.- 2. Effects on Chloride Conductance.- 3. Effects on the Sodium-Potassium Exchange Pump.- IV. Structure-Activity Relationships.- V. Regulation of Penicillin Concentration in the Central Nervous System.- VI. Nonspecific Neurotoxic Reactions.- L. Disulfiram-Like Reactions.- M. Newer ?-Lactams.- References.- 17 Therapeutic Application of ?-Lactam Antibiotics.- A. Introduction.- B. Penicillins in the Therapy of Human Infections.- I. The Penams: The Biosynthetic or Natural Penicillins.- 1. Penicillin G (Benzylpenicillin).- 2. Penicillin V and the Acid-Stable Phenoxypenicillins.- II. The Penicillinase-Resistant Penicillins.- 1. Methicillin.- 2. Nafcillin.- 3. Isoxazolyl Penicillins.- III. The Broad-Spectrum Aminopenicillins.- 1. Ampicillin.- 2. Esters of Ampicillin.- 3. Amoxicillin.- 4. Epicillin and Cyclacillin.- IV. The Antipseudomonal Penicillins.- 1. Carbenicillin.- 2. Ticarcillin.- V. The Amidinopenicillanic Acids — Amdinocillin.- VI. The Atypical ?-Lactams.- 1. The Monocyclic ?-Lactams.- 2. The Oxapenams.- 3. The Carbapenems.- 4. The Penems.- C. Cephalosporins in the Therapy of Human Infections.- I. Cephalothin.- II. Cephaloridine.- III. Cefazolin.- IV. Cefamandole.- V. Cefoxitin.- VI. Cefmetazole.- VII. Cefuroxime.- VIII. Ceforanide.- IX. Cefonicid.- X. Third-Generation Cephalosporins.- 1. Cefotaxime.- 2. Ceftizoxime.- 3. Moxalactam.- 4. Cefoperazone.- 5. Ceftriaxon.- 6. Cefmenoxime.- 7. Ceftazidime.- 8. Cefotiam.- 9. Cefsulodin.- XI. The Oral Cephalosporins.- 1. Cephalexin.- 2. Cephradine.- 3. Cefatrizine.- 4. Cefaclor.- 5. Cefroxadine, Cefadroxil, and Cephaloglycin.- D. Antibacterial Chemoprophylaxis with the ?-Lactam Antiobiotics.- I. Prophylactic Uses in Medicine.- II. Prophylactic Uses in Surgery.- E. Use of ?-Lactam Antibiotics in Dental Medicine.- F. Use of ?-Lactam Antibiotics in Veterinary Practice.- References.