比较在肉汤及人工痰液培养基中多黏菌素E对鲍曼不动杆菌的杀菌效果  

The bactericidal effect of colistin against Acinetobacter baumannii in broth versus artificial sputum medium

作　　者：曲星伊 刘笑芬 卞星晨 陈渊成[2] 张菁[2] QU Xingyi;LIU Xiaofen;BIAN Xingchen;CHEN Yuancheng;ZHANG Jing(Institute of Antibiotics,Huashan Hospital,Fudan University,Key Laboratory of Clinical Pharmacology of Antibiotics,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院抗生素研究所,国家卫健委抗生素临床药理重点实验室,上海200040 [2]复旦大学附属华山医院Ⅰ期临床研究中心,上海200040

出　　处：《中国感染与化疗杂志》2021年第2期194-200,共7页Chinese Journal of Infection and Chemotherapy

基　　金：国家科技重大专项(2017ZX09304005);上海市科委课题产学研医项目(17DZ1910402);上海市科学技术委员会项目(19411964900);2019年国家级大学生创新创业训练计划项目(201910246070)。

摘　　要：目的探究阳离子调节MH肉汤和人工痰液培养基中,多黏菌素E对碳青霉烯类抗生素耐药鲍曼不动杆菌的杀菌效果。方法选取碳青霉烯类抗生素耐药的鲍曼不动杆菌菌株,通过静态杀菌曲线考察在阳离子调节MH肉汤、人工痰液培养基中多黏菌素E对鲍曼不动杆菌的杀菌效果,并建立模型预测细菌生长及多黏菌素E在不同浓度下的杀菌作用。结果人工痰液培养基中1×MIC的多黏菌素E对鲍曼不动杆菌的杀菌效果与阳离子调节MH肉汤相当,相较于0 h,24 h的菌落数对数值不变或下降1 lgCFU/mL。体外药动学/药效学模型显示,相较于阳离子调节MH肉汤,在人工痰液培养基中鲍曼不动杆菌(AB170428和AB070311)存在生长滞后及药物作用滞后现象,生长速率常数更高(0.733 h^(-1)对0.957 h^(-1);0.534 h^(-1)对0.951 h^(-1))。2×MIC的多黏菌素E可以达到24 h持续抑制细菌生长的作用,但人工痰液培养基中的杀菌效果弱于阳离子调节MH肉汤。结论相较于阳离子调节MH肉汤,人工痰液培养基中鲍曼不动杆菌前期生长速率较缓慢,培养基的不同使多黏菌素E对鲍曼不动杆菌杀菌作用的强弱不同。Objective To explore the effect and differences of colistin against carbapenem-resistant Acinetobacter baumannii(CRAB)in cation-adjusted Mueller-Hinton broth(CAMHB)versus artificial sputum medium(ASM).Methods Two CRAB strains were selected.Static time-kill experiment was carried out in CAMHB and ASM,separately.Pharmacokinetic/pharmacodynamic(PK/PD)models were developed to predict bacterial growth and the effect of different colistin concentrations on A.baumannii in CAMHB and ASM,respectively.Results Colistin at one-fold of minimum inhibitory concentration(MIC)showed a comparable antibacterial effect in both ASM and CAMHB,withΔlgCFU/mL unchanged or decreased by 1 from time 0 to 24 hours.In PK/PD models,ASM was associated with delayed A.baumannii growth and drug effect compared with CAMHB.However,the growth rate constants of A.baumannii(AB170428 and AB070311)were higher in ASM than in CAMHB(0.733 h^(-1) vs 0.957 h^(-1);0.534 h^(-1) vs 0.951 h^(-1)).Two-fold MIC of colistin could inhibit the growth of A.baumannii for 24 hours,but the bactericidal effect in ASM was weaker than that in CAMHB.Conclusions Compared with CAMHB,A.baumannii grows slower at early phase in ASM.The bactericidal effect of colistin against A.baumannii may be affected by culture media.

关 键 词：鲍曼不动杆菌 阳离子调节MH肉汤 人工痰液培养基 多黏菌素E 药动学/药效学模型 

分 类 号：R978.16[医药卫生—药品] R378[医药卫生—药学]