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β-内酰胺酶和外排泵过度表达对临床分离大肠埃希菌中他唑巴坦-哌拉西林耐药性的贡献。

Contribution of β-lactamase and efflux pump overproduction to tazobactam-piperacillin resistance in clinical isolates of Escherichia coli.

机构信息

Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

Int J Antimicrob Agents. 2020 Apr;55(4):105919. doi: 10.1016/j.ijantimicag.2020.105919. Epub 2020 Feb 13.

Abstract

INTRODUCTION

Tazobactam-piperacillin (TZP) is a mixture of a broad-spectrum penicillin and an irreversible β-lactamase inhibitor. TZP is effective against Gram-negative bacteria that produce extended-spectrum β-lactamases, and it is used as a first-line or second-line drug to treat serious infections.

METHODS

This study identified three TZP-resistant and two TZP-intermediate strains among 514 clinical isolates of Escherichia coli.

RESULTS

These five isolates possessed one or more β-lactamase genes, bla, bla, bla, and/or bla. The expression levels of β-lactamase genes and acrAB genes in the strains were examined by using real-time reverse transcription PCR. The total enzymatic piperacillin-degrading activity in cells was determined. Two TZP-resistance mechanisms were identified: hyperproduction of TEM-1 in the two resistant strains; and simultaneous high production of β-lactamase and efflux pump AcrAB in the two TZP-intermediate isolates. The latter are an international high-risk clone O25b:H4-ST131-H30R.

CONCLUSION

TZP resistance is still rare in clinical isolates of E. coli. However, resistance can develop on high production and/or combinations of known antimicrobial resistance mechanisms in different ways.

摘要

简介

他唑巴坦-哌拉西林(TZP)是一种广谱青霉素和不可逆β-内酰胺酶抑制剂的混合物。TZP 对产生超广谱β-内酰胺酶的革兰氏阴性菌有效,可用作治疗严重感染的一线或二线药物。

方法

本研究在 514 株临床分离的大肠杆菌中鉴定出 3 株 TZP 耐药株和 2 株 TZP 中介株。

结果

这 5 株分离株均携带一个或多个β-内酰胺酶基因 bla、bla、bla 和/或 bla。通过实时逆转录 PCR 检测菌株中β-内酰胺酶基因和 acrAB 基因的表达水平。测定细胞中总哌拉西林酶降解活性。确定了两种 TZP 耐药机制:在两株耐药株中 TEM-1 的过度产生;在两株 TZP 中介株中同时高水平产生β-内酰胺酶和外排泵 AcrAB。后者是国际高风险克隆 O25b:H4-ST131-H30R。

结论

TZP 耐药在大肠杆菌的临床分离株中仍然很少见。然而,耐药性可以通过不同方式在高产量和/或已知抗菌药物耐药机制的组合下发展。

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