A Novel Variant of KPC-179 Conferring Ceftazidime-Avibactam Resistance in a Carbapenem-Resistant Klebsiella pneumoniae Isolate.

IF 2.9 3区医学 Q2 INFECTIOUS DISEASES

Infection and Drug Resistance Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI:10.2147/IDR.S470688

Quanfeng Liao, Yu Feng, Jin Deng, Weili Zhang, Siying Wu, Ya Liu, Yi Xie, Mei Kang

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引用次数: 0

Abstract

Objective: Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) that produce Klebsiella pneumoniae carbapenemase (KPC). In this study, we report the first cases of CZA resistance to develop during treatment of CRKP infections and identify the resistance mechanism.

Methods: APB/EDTA and NG-Test CARBA5 were used to detect the production of carbapenemase, whole-genome sequencing (WGS) and conjugation experiment were used to identify potential resistance mechanisms of CZA-susceptible (HX1032) and -resistant (HX1192) K. pneumoniae isolates.

Results: HX1192 K. pneumoniae was not recognized by APB/EDTA and NG-Test CARBA5 phenotypic assays, WGS revealed it carrying a novel KPC variant, KPC-179, molecular analysis highlighted a G394A mutation, and an ATC insertion at 543 in the bla_KPC-2 gene, resulting in an A133T substitution and insertion of the amino acid S at Ambler position 183 in the protein sequence. Remarkably, this mutation restored susceptibility of imipenem (MIC = 0.25 mg/L).

Conclusion: Our study highlights the importance of monitoring susceptibility during CZA treatment and accurately detecting KPC variants.

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耐碳青霉烯类肺炎克雷伯菌菌株中产生头孢他啶-阿维菌素耐药性的 KPC-179 新型变体

研究目的头孢唑肟-阿维巴坦（CZA）是一种新型β-内酰胺/β-内酰胺酶抑制剂，对产生肺炎克雷伯菌碳青霉烯酶（KPC）的耐碳青霉烯类肺炎克雷伯菌（CRKP）具有活性。在本研究中，我们报告了首例在治疗 CRKP 感染过程中出现的 CZA 耐药性，并确定了耐药性机制：方法：使用APB/EDTA和NG-Test CARBA5检测碳青霉烯酶的产生，使用全基因组测序（WGS）和共轭实验鉴定对CZA敏感（HX1032）和耐药（HX1192）的肺炎克雷伯菌分离株的潜在耐药机制：HX1192肺炎克雷伯菌未被APB/EDTA和NG-Test CARBA5表型检测识别，WGS显示其携带新型KPC变体KPC-179，分子分析突显了G394A突变，以及blaKPC-2基因中543位的ATC插入，导致A133T置换，并在蛋白序列的安布勒183位插入氨基酸S。值得注意的是，这种突变恢复了对亚胺培南的敏感性（MIC = 0.25 mg/L）：我们的研究强调了在 CZA 治疗期间监测药敏性和准确检测 KPC 变异的重要性。

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

Infection and Drug Resistance Medicine-Pharmacology (medical)

CiteScore

5.60

自引率

7.70%

发文量

826

审稿时长

16 weeks

期刊介绍： About Journal Editors Peer Reviewers Articles Article Publishing Charges Aims and Scope Call For Papers ISSN: 1178-6973 Editor-in-Chief: Professor Suresh Antony An international, peer-reviewed, open access journal that focuses on the optimal treatment of infection (bacterial, fungal and viral) and the development and institution of preventative strategies to minimize the development and spread of resistance.