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中国西南地区耐碳青霉烯类肠杆菌科细菌中头孢他啶/阿维巴坦和氨曲南/阿维巴坦的遗传多样性和体外活性:一项单中心研究。

Genetic diversity and in vitro activity of ceftazidime/avibactam and aztreonam/avibactam against imipenem-resistant Enterobacteriaceae isolates in Southwest China: A single-centre study.

机构信息

The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Yuzhong, Chongqing, China.

College of Laboratory Medicine, Chongqing Medical University, Yuzhong, Chongqing, China.

出版信息

J Glob Antimicrob Resist. 2020 Sep;22:448-451. doi: 10.1016/j.jgar.2020.04.023. Epub 2020 May 5.

Abstract

OBJECTIVES

The aim of this study was to investigate the molecular mechanisms of imipenem resistance in Enterobacteriaceae and to assess the antimicrobial activities of ceftazidime/avibactam (CAZ/AVI) and aztreonam/avibactam (ATM/AVI) against imipenem-resistant clinical isolates in a tertiary hospital in China.

METHODS

A total of 91 imipenem-resistant Enterobacteriaceae were collected and genes encoding carbapenemases, ESBLs, AmpC β-lactamases and porins were detected using PCR. MICs and susceptibility were determined using in-house-prepared broth microdilution panels and were interpreted according to CLSI breakpoints.

RESULTS

Imipenem-resistant isolates comprising 54 Klebsiella pneumoniae, 18 Escherichia coli, 8 Enterobacter cloacae, 6 Serratia marcescens, 3 Klebsiella oxytoca and 2 Klebsiella aerogenes were collected independently. Five different carbapenemase genes were identified, namely bla (n = 60), bla (n = 14), bla (n = 11), bla (n = 4) and bla (n = 1). Among the 91 carbapenem-resistant Enterobacteriaceae (CRE), 85 isolates harboured at least one ESBL and/or AmpC gene, including 5 strains without carbapenemase-encoding genes. Moreover, 31 K. pneumoniae carried ompK35 and/or ompK36 mutations. MLST results showed that the K. pneumoniae belonged to 12 different STs, with ST11 being predominant (29/54; 53.7%). Overall, 17.6%, 25.3%, 41.8%, 65.9% and 100% of the CRE strains were susceptible to amikacin, trimethoprim/sulfamethoxazole, tetracycline, CAZ/AVI and ATM/AVI, respectively.

CONCLUSION

This study revealed that CRE isolates differ significantly in their species, STs, porins and carbapenemase genes in a single Chinese hospital. ATM/AVI exhibited potent activity against CRE isolates, even for the most notorious double-carbapenemase-producers with porin defects, whereas CAZ/AVI was active against all the non-metallo-β-lactamase-producing isolates.

摘要

目的

本研究旨在探讨肠杆菌科对亚胺培南耐药的分子机制,并评估头孢他啶/阿维巴坦(CAZ/AVI)和氨曲南/阿维巴坦(ATM/AVI)对中国一家三级医院临床分离的耐亚胺培南菌株的抗菌活性。

方法

共收集了 91 株耐亚胺培南肠杆菌科,采用 PCR 法检测碳青霉烯酶、ESBLs、AmpC β-内酰胺酶和孔蛋白基因。采用自制肉汤微量稀释板法测定 MIC 和药敏,并根据 CLSI 折点进行解释。

结果

独立收集了 54 株肺炎克雷伯菌、18 株大肠埃希菌、8 株阴沟肠杆菌、6 株黏质沙雷菌、3 株产酸克雷伯菌和 2 株产气肠杆菌组成的耐亚胺培南分离株。共鉴定出 5 种不同的碳青霉烯酶基因,即 bla(n=60)、bla(n=14)、bla(n=11)、bla(n=4)和 bla(n=1)。在 91 株耐碳青霉烯肠杆菌(CRE)中,85 株至少携带一种 ESBL 和/或 AmpC 基因,其中 5 株无碳青霉烯酶编码基因。此外,31 株肺炎克雷伯菌携带 ompK35 和/或 ompK36 突变。MLST 结果显示,肺炎克雷伯菌属于 12 种不同的 STs,以 ST11 为主(29/54;53.7%)。总的来说,17.6%、25.3%、41.8%、65.9%和 100%的 CRE 株对阿米卡星、复方磺胺甲噁唑、四环素、CAZ/AVI 和 ATM/AVI 敏感。

结论

本研究表明,在中国的一家医院中,耐碳青霉烯肠杆菌分离株在种属、STs、孔蛋白和碳青霉烯酶基因方面存在显著差异。ATM/AVI 对 CRE 分离株具有强大的活性,甚至对最具威胁性的同时携带两种碳青霉烯酶且孔蛋白缺陷的产酶株也具有活性,而 CAZ/AVI 对所有非金属-β-内酰胺酶产生株均具有活性。

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