人卫7版微生物chapter6细菌的耐药性说课材料.ppt

单击此处编辑母版标题样式单击此处编辑母版副标题样式*1Chapter6BacterialDrug-Resistancen n细菌产生的抗生素细菌产生的抗生素 多粘菌素、杆菌肽n n真菌产生的抗生素真菌产生的抗生素 青霉素、头孢菌素n n放线菌产生的抗生素放线菌产生的抗生素 放线菌放线菌是产生抗生素的主要来源； 链霉素、红霉素、卡那霉素、四环素抗菌药物（antibacterial agents）1.Inhibition of cell wall synthesis 2.Damage to the cell membrane functions 3.Interference of protein synthesis 4.Inhibition of nucleic acid synthesis AntibacterialmechanismsG+G-1.InhibitionofcellwallsynthesisThe antimicrobial mechanisms of penicillin and lysozyme 2.Damagetothecellmembrane细菌的耐药性（细菌的耐药性（drug resistancedrug resistance）l概念：亦称抗药性，是指细菌对某抗菌药物的相对抵抗性。

l耐药性的程度以该药对细菌的最小抑菌浓度(minimum inhibitory concentration, MIC）表示l临床上： 药物的治疗浓度最小抑菌浓度 敏感 药物的治疗浓度最小抑菌浓度 耐药“超级细菌” （Superbugs）“超级细菌”1.耐甲氧西林金黄色葡萄球菌（MRSA）2.抗万古霉素肠球菌（VRE）3.耐多药肺炎链球菌（MDRSP）4.多重抗药性结核杆菌（MDR-TB）5.碳青霉烯酶肺炎克雷伯菌（KPC）6.“产NDM-1耐药细菌”与传统“超级细菌”相比，其耐药性已经不再是仅仅针对数种抗生素具有“多重耐药性”，而是对绝大多数抗生素均不敏感，这被称为“泛耐药性”（pan-drugresistance,PDR）NDM-1:NewDelhi-Metallo-1 Outline1.Genetics of drug resistance 2.Biochemical mechanisms of resistance 3.Control of resistanceGeneticsofresistancenIntrinsicresistance（固有耐药性）nAcquiredresistance（获得耐药性） Intrinsicresistancen固有耐药性、天然耐药性nBacteria are insusceptible to some certain antibiotics inherently. nResistance genes are located on the chromosome and have genus specificity. Acquiredresistancen获得耐药性nAn initially susceptible species develops resistance.nReasons for acquired resistance1.Chromosomal mutation（染色体突变）2.Transferable antibiotic resistance（可传递的耐药性） Plasmids (conjugation, transformation) Transposons (transponsition) Integrons Biochemical mechanisms of resistance（细菌耐药的生化机制）1.Modified enzymes（钝化酶的产生）2.Altered targets（药物作用靶位的改变）3.Permeability barriers（抗菌药物的渗透障碍）4.Initiative efflux systems（主动外排机制）5.Other mechanisms（其他）1.Modifiedenzyme（钝化酶）nThe most powerful and robust of the resistance mechanisms.nThey may act on the antimicrobic molecule by disrupting its structure or by catalyzing a reaction that chemically modifies it.1.-lactamases (-内酰胺酶)2.Aminoglycoside-modified enzymes (氨基糖苷类钝化酶)3.Chloramphenicol acetyl transferase (氯霉素乙酰基转移酶)-lactamases（ -内酰胺酶） is a general term referring to any one of hundreds of bacterial enzymes able to break or open the -lactam ring （-内酰胺环）and inactivate various members of -lactam group （-内酰胺类抗生素）.Aminoglycoside-modified enzymes （氨基糖苷类钝化酶）may acetylate（乙酰化）, adenylate（腺苷酸化）, or phosphorylate（磷酸化） hydroxyl or amino groups on the aminoglycoside molecule.Chloramphenicol acetyltransferase （氯霉素乙酰基转移酶） may acetylate chloromycin. Aminoglycoside-modifiedenzymes（氨基糖苷类钝化酶）Alteredtargets（药物作用靶位的改变）AntibioticsTargetsPenicillin（青霉素）Penicillin-binding protein (PBP)Streptomycin（链霉素）30S subunit of ribosomeErythromycin（红霉素）50S subunit of ribosomeLosetargetsand(or)reduceaffinityPermeationbarriers（抗菌药物的渗透障碍）nThe bacterial cell wall and outer membrane permeability barriers （细菌细胞壁障碍或外膜通透性的改变）will seriously affect the antimicrobial effectiveness. nResistance shielding（耐药屏蔽）is an important resistance mechanism.Initiative efflux systems（主动外排机制）主动外排系统示意图第三节 细菌耐药性的防治n合理使用抗菌药物n严格执行消毒隔离制度n加强药政管理n研制新抗菌药物n破坏耐药基因Drug sensitivity test （药敏试验）Importantpoints1.Intrinsicresistance2.Acquiredresistance3.Biochemicalmechanismsofbacterialdrug-resistance。