摘要
目的了解头孢他啶/阿维巴坦(CZA)单用或与氨曲南(ATM)联合用药对耐碳青霉烯类肠杆菌目细菌(CRE)的体内、外抗菌活性,为临床抗感染治疗提供依据。方法采用微量肉汤稀释法对某院2018-2022年临床分离的52株非重复CRE进行CZA及ATM最低抑菌浓度(MIC)测定,采用棋盘稀释法进行联合药敏试验。时间-杀菌曲线和大蜡螟感染模型检测CZA单用或与ATM联合使用的杀菌效果。结果23株产KPC酶的CRE菌株中91.3%(21株)对CZA的MIC≤4μg/mL,8.7%(2株)的菌株对CZA的MIC≥128μg/mL。产NDM、IMP、KPC+IMP、KPC+NDM等酶型的29株CRE对CZA的MIC值均≥128μg/mL。31株CZA耐药的菌株中93.5%(29株)的CZA与ATM联合FIC值<0.5,6.5%(2株)的FIC在0~1。时间-杀菌曲线表明CZA对产KPC酶的菌株具有杀菌效果,CZA联合ATM对耐CZA菌株有杀菌效果。与单药组相比,CZA联合ATM处理组CRE感染大蜡螟生存率显著提高(中位生存时间120 h,P=0.001)。结论CZA对产KPC酶的细菌有较好的抗菌作用。CZA与ATM联用对CZA耐药的菌株具有协同抑菌作用。
Objective To investigate the in vivo and in vitro antimicrobial activity of ceftazidime/avibactam(CZA)alone or in combination with aztreonam(ATM)against carbapenem-resistant Enterobacterales(CRE),and provide evidence for clinical anti-infective therapy.Methods The minimum inhibitory concentrations(MICs)of CZA and ATM against 52 clinically isolated non-repetitive CRE strains in a hospital from 2018 to 2022 were determined with microbroth dilution method,and the combined antimicrobial susceptibility testing was performed with the chessboard dilution method.Time-killing curve and Galleria mellonella infection model were used to test the bactericidal effect of CZA alone or in combination with ATM.Results Among the 23 KPC-producing CRE strains,91.3%(n=21)had MIC≤4μg/mL for CZA,and 8.7%(n=2)had MIC≥128μg/mL for CZA.MIC of CZA to 29 CRE strains(strains producing NDM,IMP,KPC+IMP,and KPC+NDM)were all≥128μg/mL.Of the 31 CZA-resistant strains,93.5%(n=29)strains had fractional inhibitory concentration(FIC)<0.5 for combination of CZA and ATM,while 6.5%(n=2)had FIC of 0-1.The time-killing curve showed that CZA had bactericidal effect on KPC-producing strains,and CZA combined with ATM had bactericidal effect on CZA-resistant strains.Compared with the monotherapy group,CZA combined with ATM treatment significantly improved the survival rate of CRE-infected Galleria mellonella(median survival time 120 hour,P=0.001).Conclusion CZA has good antimicrobial activity against KPC-producing bacteria.The combination of CZA and ATM had synergistic bacteriostatic effect on CZA-resistant strains.
作者
卞丽娟
郭俊哲
郑美娟
BIAN Li-juan;GUO Jun-zhe;ZHENG Mei-juan(Department of Laboratory Medicine,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Laboratory Medicine,The Fifth People’s Hospital of Bengbu,Bengbu 233099,China;Clinical College of Anhui Medical University,Hefei 230032,China)
出处
《中国感染控制杂志》
CAS
CSCD
北大核心
2024年第10期1206-1212,共7页
Chinese Journal of Infection Control
基金
安徽省高校自然科学研究项目(KJ2021A0761)。
