Chloramphenicol（氯霉素）.pptVIP

Aminoglycosides（氨基糖苷类）, Macrolides（大环内酯类）and others 2011.12 Aminoglycosides（氨基糖苷类） Tuberculosis, still severe infection now 1882, Heinrich Hermann Robert Koch discovered M. tuberculosis （结核分枝杆菌） 1940’s, Merck supported S.A. Waksman’s lab, Rutgers university, NJ 1940, actinomycin（放线菌素）, toxic 1942, streptothricin （链丝菌素），still toxic 1942, Albert Schatz, PhD student Aminoglycosides（氨基糖苷类） Individual aminoglycosides Streptomycin（链霉素） Gentamycin（庆大霉素） Amikacin（氨苄卡星） Tobramycin（妥布霉素） Netilmycin（奈替米星） aminoglycosides Common characters: Potent effect on Gram- bacteria, including Pseudomonas, Mycobacterium tuberculosis Ineffective against anaerobic bacteria Not absorbed orally Untoward effects: 5 days; high dose; elderly; renal insufficiency ototoxicity（2％-10％）: vertigo（眩晕）, ataxia（共济失调）, loss of banlance nephrotoxicity（6％-10％） neuromuscular blocking (co-administered with general analgesics or muscle relaxants) Toxicity Their undesirable side effects: severe ototoxicity and nephrotoxicity. 18 of 21 actress showing “qianshou guanyin” were caused deafness by aminoglycosides. aminoglycosides Mechanism: binding to the S12 Protein of the 30S subunit of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit Resistance to aminoglycosides aminoglycoside-modifying enzymes (钝化酶) Phosphoryltransferases（磷酰转移酶） Acetyltransferases（乙酰转移酶） Adenylyltransferases（腺苷酰转移酶） Polymyxins 多黏菌素 Polymyxins（多粘菌素类） polymyxins detergents, selectively toxic for Gram- bacteria due to their specificity for the lipopolysaccharide（脂多糖） molecule strong nephrotoxic renewed interest duo to antimicrobial resistance Macrolides（大环内酯类） Macrolides（大环内酯类） macrolides Antibacterial spectrum: similar or wider anti-bacterial spectrum than penicillin (replacing penicillin for allergic patients) some G- bacteria: Legionella pneum