文档介绍：陈佰义
中国医科大学附属第一医院
经验性抗感染治疗
-药物选择的基本原则与临床实践
抗感染药物发展简史
1929 Alexander Fleming 发现青霉素
Howard Florey 和 Ernst Chain分离获得青霉素,用于动物试验。
青霉素首次用于救治战伤患者,拯救了许多人的生命
1950’s 大量抗生素用于临床。
A poster from World War II, dramatically showing the virtues of the new miracle drug, and representing the high level of motivation in the country to aid the health of the soldiers at war.
Discovery of Antibacterial Agents
Cycloserine
Erythromycin
Ethionamide
Isoniazid
Metronidazole
Pyrazinamide
Rifamycin
Trimethoprim
ycin
Virginiamycin
Imipenem
1930
1940
1950
1960
1970
1980
1990
2000
Penicillin
Prontosil
Cephalosporin C
Ethambutol
Fusidic acid
Mupirocin
Nalidixic acid
Oxazolidinones
Cecropin
Fluoroquinolones
Newer aminoglycosides
Semi-synthetic penicillins & cephalosporins
Newer carbapenems
Trinems
Synthetic approaches
Empiric screening
Newer macrolides & ketolides
Rifampicin
Rifapentine
Semi-synthetic glycopeptides
Semi-synthetic streptogramins
Neomycin
Polymixin
Streptomycin
Thiacetazone
Chlortetracycline
Glycylcyclines
Minocycline
Chloramphenicol
“Close the book on infectious disease”
“Infectious disease will be with us for
the foreseeable future”
US Surgeon General
William Stewart, 1969
Harvard Medical School
Mary Wilson, 1998
抗生素时代感染仍是人类健康的重要威胁
IIIIIIII
新出现或“再出现”的感染性疾病 emerging and re-emerging infectious diseases
新病原体不断出现-HIV/AIDS、Ebola、Hantavirus
新型肝炎、新型克-雅病(疯牛病)肠杆菌O157、霍乱O139
环孢子菌病、隐孢子菌病、人类Ehrlichosis…
老病卷土重来-肺结核、疟疾、鼠疫、霍乱、黄热病、登革热
和登革出血热…
免疫缺陷人群不断增加-机会性真菌和呼吸道病毒性肺炎…
细菌耐药愈演愈烈-PRSP、MRSP、MRSA/MRSE、VRE、VISA/VERA…
-ESBL、ampC、SSBL、金属酶….
-MDR结核菌…

美国因细菌耐药增加医疗费用超过40亿美元!!
临床关注的耐药问题Resistances of Clinical Concerns
革兰阳性细菌
金匍菌– MRSA, VISA, VRSA
VRE (地理上差别)
肺炎链球菌–青霉素和喹诺酮耐药
革兰阴性细菌
肠杆菌科-ESBLs
喹诺酮,头孢菌素,青霉素类,氨基糖苷类
碳青霉烯类
非发酵菌(假单孢菌+/-不动杆菌)
喹诺酮, 头孢菌素,青霉素类,氨基糖苷类,碳青霉烯类
Resistant bacteria
Mutations
XX
Antibiotic resistance: ic events
Susceptible bacteria
Resistant bacteria
Gene transfer
Resistant StrainsRare
x
x
Resistant Strains
Dominant
An