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耐碳青霉烯铜绿假单胞菌临床分离株中头孢他啶-阿维巴坦耐药的流行情况和分子特征。

Prevalence and molecular characteristics of ceftazidime-avibactam resistance among carbapenem-resistant Pseudomonas aeruginosa clinical isolates.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Glob Antimicrob Resist. 2024 Mar;36:276-283. doi: 10.1016/j.jgar.2024.01.014. Epub 2024 Feb 1.

Abstract

OBJECTIVES

Resistance against ceftazidime-avibactam (CZA) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) is emerging. This study was aimed at detecting the prevalence and molecular characteristics of CZA-resistant CRPA clinical isolates in Guangdong Province, China.

METHODS

The antimicrobial susceptibility profile of these strains was determined. A subset of 16 CZA-resistant CRPA isolates was analysed by whole-genome sequencing (WGS). Genetic surroundings of carbapenem resistance genes and pan-genome-wide association analysis were further studied.

RESULTS

Of the 250 CRPA isolates, CZA resistance rate was 6.4% (16/250). The minimum inhibitory concentration (MIC) of CZA range was from 0.25 to >256 mg/L. MIC and MIC were 2/4 and 8/4 mg/L, respectively. Among the 16 CZA-resistant CRPA strains, 31.3% (5/16) of them carried class B carbapenem resistance genes, including bla, bla, and bla, located on IncP-2 megaplasmids or chromosomes, respectively. Pan-genome-wide association analysis of accessory genes for CZA-susceptible or -resistant CRPA isolates showed that PA1874, a hypothetical protein containing BapA prefix-like domain, was enriched in CZA-resistant group significantly.

CONCLUSIONS

Class B carbapenem resistance genes play important roles in CZA resistance. Meanwhile, the PA1874 gene may be a novel mechanism involving in CZA resistance. It is necessary to continually monitor CZA-resistant CRPA isolates.

摘要

目的

耐头孢他啶-阿维巴坦(CZA)的铜绿假单胞菌(CRPA)正在出现。本研究旨在检测中国广东省耐 CZA 的 CRPA 临床分离株的流行率和分子特征。

方法

测定这些菌株的抗菌敏感性谱。通过全基因组测序(WGS)分析了 16 株耐 CZA 的 CRPA 分离株的亚组。进一步研究了碳青霉烯类耐药基因的遗传环境和泛基因组关联分析。

结果

在 250 株 CRPA 分离株中,CZA 耐药率为 6.4%(16/250)。CZA 的最小抑菌浓度(MIC)范围为 0.25 至>256mg/L。MIC 和 MIC 分别为 2/4 和 8/4mg/L。在 16 株耐 CZA 的 CRPA 菌株中,31.3%(5/16)携带 B 类碳青霉烯类耐药基因,包括 blaCTX-M-15、blaOXA-23-like 和 blaVIM-1,分别位于 IncP-2 大型质粒或染色体上。对 CZA 敏感或耐药 CRPA 分离株的辅助基因进行泛基因组关联分析显示,PA1874,一种含有 BapA 前缀样结构域的假定蛋白,在 CZA 耐药组中显著富集。

结论

B 类碳青霉烯类耐药基因在 CZA 耐药中起重要作用。同时,PA1874 基因可能是一种涉及 CZA 耐药的新机制。有必要持续监测耐 CZA 的 CRPA 分离株。

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