Team Resist, UMR1184, Immunology of Viral, Auto-Immune, Hematological, and Bacterial Diseases, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, Le Kremlin-Bicêtre, France.
Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriaceae, Le Kremlin-Bicêtre, France.
Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0116021. doi: 10.1128/AAC.01160-21. Epub 2021 Oct 4.
Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European health care settings.
对头孢他啶（CAZ）-阿维巴坦（AVI）联合用药的耐药性日益受到关注。在此，我们报告了一株属于高风险序列型 307（ST307）克隆的 CAZ-AVI 耐药肺炎克雷伯菌，该菌产生肺炎克雷伯菌碳青霉烯酶 39（KPC-39），是 KPC-3 的单一氨基酸变异体（A172T）。克隆实验、稳态动力学参数和分子动力学模拟揭示了碳青霉烯酶活性的丧失和对 CAZ 的亲和力增加。在未接触 CAZ-AVI 的患者中发现了 KPC-39，提示其在欧洲医疗机构中存在隐匿传播。
