新发传染病电子杂志2025，Vol.10Issue(6)：24-31,8.DOI:10.19871/j.cnki.xfcrbzz.2025.05.004
新型β-内酰胺酶抑制剂复合制剂对碳青霉烯耐药肺炎克雷伯菌体外药物敏感性研究
Activity of novel β-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae:an in vitro study
摘要
Abstract
Objective To systematically elucidate the susceptibility profiles of carbapenem-resistant Klebsiella pneumoniae(CRKP)to novel β-lactamase inhibitor combinations through integrated bioinformatics analysis and in vitro antimicrobial susceptibility testing,thereby providing scientific evidence for optimizing clinical anti-infective treatment strategies.Method Performed broth micr-dilution assays to evaluate the susceptibility of 146 CRKP clinical isolates(collected from March to August 2023)to relebactam-,vaborbactam-,avibactam-,and taniborbactam-based combination regimens.Whole-genome sequencing was conducted,and molecular characteristics were analyzed using Kleborate.Phylogenetic reconstruction was performed using Snippy.Result Antimicrobial susceptibility testing demonstrated that β-lactam/β-lactamase inhibitor combinations(imipenem-relebactam,meropenem-vaborbactam,ceftazidime-avibactam,aztreonam-avibactam,fcefepime-taniborbactam)exhibited significantly enhanced activity compared to monotherapies,with minimum inhibitory concentrations(MICs)decreased to 1/32 of the original value or lower,the susceptibility rates of all tested compound formulations exceeded 90%.Aztreonam-Avibactam(100%)and Fcefepime-Taniborbactam(99.3%)showed the highest efficacy.Molecular analysis revealed ST11(84.2%)and KL64(79.4%)as predominant sequence and capsular types,respectively.Carbapenem resistance was primarily mediated by blaKPC-2(90.4%),while high-frequency mutations in OmpK35(91.8%)and OmpK36(84.3%)also constituted the resistance mechanisms.Phylogenetic analysis indicated polyclonal transmission,with OXA-232-producing strains forming distinct clusters,suggesting potential adaptive advantages.Conclusion Novel β-lactamase inhibitor combinations demonstrated potent activity against CRKP isolates in our hospital.However,the emergence of resistant strains underscores the need for further investigation into resistance mechanisms and enhanced epidemiological surveillance.关键词
碳青霉烯耐药肺炎克雷伯菌/新型β-内酰胺酶抑制剂/体外药物敏感性Key words
Carbapenem-resistant Klebsiella pneumoniae/Novel β-lactamase inhibitors/In vitro antimicrobial susceptibility分类
医药卫生引用本文复制引用
马克,张宝芳,徐伟,张权..新型β-内酰胺酶抑制剂复合制剂对碳青霉烯耐药肺炎克雷伯菌体外药物敏感性研究[J].新发传染病电子杂志,2025,10(6):24-31,8.基金项目
1.贵州省教育厅自然科学研究项目(青年科技人才成长项目)(黔教技[2024]103号) （青年科技人才成长项目）
2.贵州省卫生健康委科学技术基金项目(gzwkj2025-012) （gzwkj2025-012）
3.贵州医科大学校重点实验项目-感染性疾病与肝病重点实验室([2024]fy006号) （[2024]fy006号）
