Chpt 42 中Beta-lactam antibiotics β-内酰胺类抗生素.pptVIP

化学结构 1. Chemistry Basic Structure 2. Classification of Penicillins  (1) Penicillins inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis. Penicillins are structural analogs of the natural D-Ala-D-Ala substrate and they are covalently bound by PBPs (penicillin binding proteins, transpeptidases) at the active site. After Penicillin has attached to the PBPs, the transpeptidation reaction is inhibited and the cell wall is induced to break down.   (2) Penicillins also induce and enhance the activity of the autolytic enzymes (autolysin), resulting in lysis of microorganism in an isotonic environment. 4. Mechanism of bacterial resistance to penicillins (1) Inactivation of antibiotic by beta-lactamase, (2) Modification of target PBPs, (3) Impaired penetration of drug to target PBPs, (4) The presence of an efflux pump. 5. Spectrum of activity and clinical uses  (2) CLINICAL USES a) Penicillin G is the drug of choice for infections caused by streptococci, meningococci, enterococci, penicillin-susceptible pneumococci, non-beta-lactamase-producing staphylococci, Treponema pallidum and many other spirochetes, Bacillus anthracis, clostridium species, actinomyces, and other G+ rods and non-beta-lactamase-producing G- anaerobic organisms.  b) The simultaneous administration of the relevant antitoxin is often necessary for the treatment of diphtheria 白喉and tetanus破伤风. c) The combination of an aminoglycoside is also necessary for bactericidal effects in enterococcal endocarditis.  (oxacillin 苯唑西林, cloxacillin 氯唑西林, dicloxacillin双氯西林, nafcillin萘夫西林) They are the drugs of first choice for treating infections of the penicillinase-producing aurococcus. (ampicillin 氨苄西林, amoxicillin 阿莫西林) They are similar to penicillin G in the activity against gram-positive organisms but are weaker than the latter. They are more satisfactory for the treatment of enterococci and str