阴沟肠杆菌对碳青霉烯类药物的耐药机制

Antimicrobial resistance mechanism of Enterobacter cloacae to carbapenems

摘要:

目的 研究耐碳青霉烯类阴沟肠杆菌分子流行病学特征和碳青霉烯耐药机制，为临床经验性用药及医院感染防控提供依据。 方法 对某院2019年4—9月分离的耐碳青霉烯类阴沟肠杆菌进行菌种鉴定及药敏分析，mCIM联合eCIM试验筛选碳青霉烯酶，聚合酶链反应（PCR）方法检测碳青霉烯酶耐药基因，多位点序列分型（MLST）和脉冲场凝胶电泳（PFGE）进行分子流行病学特征分析。 结果 8株耐碳青霉烯类阴沟肠杆菌中5株来自于重症监护病房（ICU），对临床常用头孢类及加酶抑制剂药物均表现出高水平耐药的特性。所有菌株均携带金属β-内酰胺酶，7株为bla_NDM-1，1株为bla_IPM-4。MLST分子分型及PFGE同源性分析有6个ST序列类型，6个克隆群。ST596（3株）均为A群、ST121（1株）为C群、ST993（1株）为F群、ST91（1株）为E群、ST794（1株）为B群、ST88（1株）为D群。 结论 该院耐碳青霉烯类阴沟肠杆菌主要来源于ICU，产金属酶bla_NDM-1β-内酰胺酶是其主要耐药机制。ST596 A群阴沟肠杆菌短时间内在ICU存在局部流行，应加强医院感染防控措施，遏制暴发流行。

Abstract:

Objective To study the molecular epidemiological characteristics of carbapenem-resistant Enterobacter cloacae (CREC) and mechanism of carbapenem resistance, provide basis for clinical empirical antimicrobial use as well as prevention and control of healthcare-associated infection. Methods CREC isolated from a hospital between April and September 2019 were identified and performed antimicrobial susceptibility analysis, carbapenemase was screened by modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM), carbapenem-resistant genes were detected by polymerase chain reaction (PCR), molecular epidemiological characteristics were analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Results Among 8 strains of CREC, 5 were from intensive care unit (ICU) and were highly resistant to cephalosporins and enzyme inhibitors commonly used in clinical practice. All strains carried metallo-β-lactamases, 7 strains carried bla_NDM-1 and 1 strain carried bla_IPM-4. MLST molecular typing and PFGE homology analysis showed 6 ST sequence types and 6 clone groups. ST596 (3 strains), ST121 (1 strain), ST993 (1 strain), ST91 (1 strain), ST794 (1 strain) B and ST88 (1 strain) belonged to groups A, C, F, E, B and D respectively. Conclusion CREC in this hospital mainly comes from ICU, producing of metalloenzyme bla_NDM-1 β-lactamase is the main resistance mechanism. ST596 group A Enterobacter cloacae has local epidemic in ICU for a short time, prevention and control measures of HAI should be strengthened to curb the outbreak.