Diverse modes of ceftazidime/avibactam resistance acquisition in carbapenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa from a Chinese intensive care unit.

IF 4.6 2区医学 Q1 MICROBIOLOGY

Annals of Clinical Microbiology and Antimicrobials Pub Date : 2025-05-30 DOI:10.1186/s12941-025-00800-z

Junxin Zhou, Minhua Chen, Min Liang, Xinhong Han, Rui Weng, Yue Li, Yan Jiang, Xiaoting Hua, Xiaoxing Du, Weiping Wang, Zhihui Zhou, Yunsong Yu

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引用次数: 0

Abstract

Objectives: To investigate the mechanisms of ceftazidime/avibactam (CZA) resistance and the nosocomial dissemination of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) in an intensive care unit (ICU) in China.

Methods: Clinical CRPA and CRKP isolates were obtained from an ICU of a tertiary hospital in China from August 2020 to February 2021. Antimicrobial susceptibility was determined according to CLSI. WGS, cloning experiments and kinetic parameters were conducted to reveal resistance mechanisms, molecular characteristics and dissemination of CRPA and CRKP.

Results: We isolated 32 CZA-resistant strains, including 12 CRPA and 20 CRKP strains from an ICU between August 2020 and February 2021. CZA resistance was associated with the presence of NDM and efflux pumps in CRKP strains, whereas bla_AFM-2, bla_KPC-87, and bla_PER-1 contributed to CZA resistance in CRPA strains. Compared to KPC-2, KPC-87 exhibited a 1.5-fold elevation in k_cat/K_m for ceftazidime, a 7.5-fold increase in K_i for avibactam, and a loss of carbapenem hydrolysis. bla_KPC-87 was located in the NTE_KPC-IIa like element based on the Tn3. Insertion of 656 bp Δbla_TEM-1 upstream of bla_KPC-87 introduced an additional promoter that increased KPC-87 expression. Cluster 2 and 3 of CRKP represented two different clones of ST11 transmitted between patients. KPC-87-producing ST270 CRPA strains exhibited a small-scale dissemination and cross-regional transfer with the referral of a patient. The evolutionary pathways of AFM-2-producing ST275 CRPA strains were more complex to elucidate the transmission events.

Conclusions: In CRKP and CRPA, diverse resistance mechanisms contributed to CZA resistance. These CZA-resistant strains were transmitted among patients in the ICU and even across regions to the other healthcare unit when the patient was transferred.

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中国重症监护病房碳青霉烯耐药肺炎克雷伯菌和铜绿假单胞菌头孢他啶/阿维巴坦耐药获得的不同模式

目的：探讨中国重症监护病房（ICU）耐碳青霉烯类铜绿假单胞菌（CRPA）和耐碳青霉烯类肺炎克雷伯菌（CRKP）的头孢他啶/阿维巴坦（CZA）耐药机制及院内传播情况。方法：于2020年8月至2021年2月在国内某三级医院ICU获得临床CRPA和CRKP分离株。采用CLSI法测定药敏。通过WGS、克隆实验和动力学参数分析，揭示了CRPA和CRKP的耐药机制、分子特性和传播情况。结果：我们在2020年8月至2021年2月期间从ICU分离到32株cza耐药菌株，其中CRPA 12株，CRKP 20株。CRKP菌株对CZA的耐药与NDM和外排泵的存在有关，而CRPA菌株对CZA的耐药与blaAFM-2、blaKPC-87和blaPER-1有关。与KPC-2相比，KPC-87对头孢他啶的kcat/Km升高1.5倍，对阿维巴坦的Ki升高7.5倍，并且碳青霉烯类酶水解缺失。blaKPC-87位于基于Tn3的NTEKPC-IIa类元素中。在blaKPC-87上游插入656 bp ΔblaTEM-1引入了一个额外的启动子，增加了KPC-87的表达。CRKP的聚类2和聚类3代表两种不同的ST11克隆在患者间传播。产kpc -87的ST270 CRPA菌株随着患者转诊呈现小规模传播和跨区域转移。产生afm -2的ST275 CRPA菌株的进化途径更为复杂，无法解释其传播事件。结论：在CRKP和CRPA中，多种耐药机制促成了CZA的耐药。这些抗cza菌株在ICU的患者之间传播，甚至在患者转院时跨地区传播到其他医疗保健单位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Clinical Microbiology and Antimicrobials MICROBIOLOGY-

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.