替加环素对4种耐药菌体外抗菌活性及其药效学评价

In vitro activities of tigecycline agaist four kinds of resistant bacteria and evaluate the pharmacodynamic of tigecycline

目的测定替加环素对4种耐药菌的体外抗菌作用并对其药效学进行评价。方法采用微量肉汤稀释法测定替加环素对453株耐甲氧西林的金黄色葡萄球菌,421株泛耐药鲍曼不动杆菌,124株耐万古霉素的肠球菌以及235株产ESBLs的大肠埃希菌的最低抑菌浓度(MIC)。整理已发表的替加环素的药代动力学资料,设置AUC24/MIC>18对革兰阳性菌、AUC24/MIC>6.96对革兰阴性菌为替加环素的药效学目标,利用Crystal Ball软件模拟出5000例患者的目标获得概率并计算得出累积反应分数。结果替加环素对耐甲氧西林的金黄色葡萄球菌、耐万古霉素的肠球菌、产ESBLs的大肠埃希菌的敏感率为100%,对泛耐药鲍曼不动杆菌的敏感率仅为54.5%。蒙特卡罗模拟结果显示,对于耐甲氧西林的金黄色葡萄球菌、耐万古霉素的肠球菌、产ESBLs的大肠埃希菌,替加环素50mg剂量组的累积反应分数均达到90%以上。而替加环素50mg剂量组对泛耐药鲍曼不动杆菌的累积反应分数为13.34%,即使将药物剂量增加到100mg其累积反应分数也只有15.55%。结论除泛耐药的鲍曼不动杆菌外,替加环素对耐甲氧西林的金黄色葡萄球菌、耐万古霉素的肠球菌、产ESBLs的大肠埃希菌有很好的抗菌活性,临床上应用替加环素治疗泛耐药鲍曼不动杆菌可能无法达到理想的治疗效果。

Objective To determine the in vitro activity of tigecycline against four kinds of resistant bacteria and evaluate the pharmacodynamic of tigecycline. Methods The minimal inhibitory concentrations （MIC） of tigecycline against 453 strains of methicillin-resistant Staphylococcus aureus（MRSA）, 421 strains of pan-drug resistant Acinetobacter baumannii（PDR-AB）, 124 strains of vancomycin-resistant enterococci（VRE）, and 235 strains of ESBL-producing E. coil were determined by the broth microdilution method. The population pharmacokinetic data of tigecycline reported previously were used to set up AUC24/MIC〉18 for Gram-positive and AUC24/MIC〉6.96 for Gram-negative as the pharmacodynamic targets. The PTA and CFR of 5000 patients were simulated using Crystal Ball software. Results The tigecycline susceptibility rates were 100% for MRSA, VRE, ESBL-producing E. coli and 54.5% for PDR-AB. Monte Carlo simulation results show that the CFR of tigecycline 50rag dose group for MRSA, VRE, ESBL-producing E. coli were more than 90% and 13.34% for PDR-AB, even increasing to 100mg doses the CFR for PDR-AB was 15.55%. Conclusion Except for PDR-AB, tigecycline is a novel broad spectrum antimicrobial that is active against MRSA, VRE and ESBL-producing E. coll. Clinically applied for treatment of PDR- AB may not be able to achieve ideal therapeutic effect.