In vitro activity of zidebactam/cefepime (WCK 5222), a β-lactam enhancer/ β-lactam combination against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates

IF 2.1 4区医学 Q3 INFECTIOUS DISEASES

Diagnostic microbiology and infectious disease Pub Date : 2024-10-12 DOI:10.1016/j.diagmicrobio.2024.116561

Yamuna Devi Bakthavatchalam , Chaitra Shankar , Christo Jeyaraj , Ayyanraj Neeravi , Purva Mathur , Vasant Nagvekar , Sangeetha Nithiyanandam , Kamini Walia , Balaji Veeraraghavan

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引用次数: 0

Abstract

Objectives

In vitro activity of β-lactam enhancer/β-lactam combination zidebactam/cefepime was evaluated against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates.

Methods

Non duplicate K. pneumoniae (n=185), resistant to colistin as well as non-susceptible to carbapenems were collected (2018-2019) at two large tertiary care hospitals in India. Colistin resistance-conferring genes mcr1 and mcr3 were screened among 123 of 185 randomly-selected isolates. These isolates were also subjected to multi-locus sequence typing (MLST). Additionally, alterations in mgrB were screened in 109 of these 123 isolates. All the study isolates were screened for presence of carbapenemases genes. MICs of zidebactam/cefepime, colistin, carbapenems, ceftazidime/avibactam, imipenem/relebactam, amikacin and piperacillin/tazobactam were determined by reference CLSI broth dilution method.

Results

Among the isolates, 65.4% (121/185) carried bla_OXA-48-like gene and 27.6% isolates (51/185) carried dual carbapenemase genes; bla_OXA-48-like and bla_NDM. Of the remainder, 8 isolates carried bla_NDM and 5 isolates lacked carbapenemases gene despite being carbapenem-resistant. None of the isolates showed presence of mcr1 and mcr3. Out of 109 isolates analysed for mgrB, 36 showed mutational changes. The MLST profile revealed at least 14 unique sequence types with ST231 being the dominant clone. All the isolates showed colistin MICs >2 mg/L and were non-susceptible to carbapenems. Zidebactam/cefepime demonstrated potent activity with MIC₅₀ and MIC₉₀ of 1 and 2 mg/L, respectively. MIC₉₀s of amikacin, ceftazidime/avibactam and imipenem/relebactam were >32 mg/L.

Conclusion

Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant K. pneumoniae isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism.

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zidebactam/cefepime (WCK 5222)是一种β-内酰胺增强剂/β-内酰胺复方制剂，对耐碳青霉烯类和耐秋水仙碱肺炎克雷伯菌分离物的体外活性。

目的评估β-内酰胺增强剂/β-内酰胺组合齐德巴坦/头孢吡肟对碳青霉烯类和耐可乐定肺炎克雷伯菌分离株的体外活性：在印度两家大型三级医院收集了对可乐定耐药和对碳青霉烯类不耐药的非重复肺炎克雷伯菌（n=185）（2018-2019年）。在随机挑选的 185 个分离株中，对 123 个分离株的耐药基因 mcr1 和 mcr3 进行了筛查。还对这些分离株进行了多焦点序列分型（MLST）。此外，还对这 123 个分离株中的 109 个进行了 mgrB 变异筛查。对所有研究分离物进行了碳青霉烯酶基因筛选。参照 CLSI 肉汤稀释法测定了齐德巴坦/头孢吡肟、考来霉素、碳青霉烯类、头孢他啶/阿维菌素、亚胺培南/雷巴坦、阿米卡星和哌拉西林/他唑巴坦的 MIC 值：在分离菌株中，65.4%（121/185）携带 blaOXA-48-like 基因，27.6%（51/185）携带双重碳青霉烯酶基因；blaOXA-48-like 和 blaNDM。其余分离物中，8 个携带 blaNDM 基因，5 个缺乏碳青霉烯酶基因，但对碳青霉烯类耐药。没有一个分离物显示存在 mcr1 和 mcr3。在分析了 109 个 mgrB 分离物中，有 36 个出现了突变。MLST 图谱显示至少有 14 种独特的序列类型，其中 ST231 是主要的克隆。所有分离菌株的可乐定 MIC 均大于 2 毫克/升，对碳青霉烯类不敏感。齐德巴坦/头孢吡肟具有很强的活性，其 MIC50 和 MIC90 分别为 1 毫克/升和 2 毫克/升。阿米卡星、头孢他啶/阿维菌素和亚胺培南/雷巴坦的 MIC90 均大于 32 毫克/升：结论：齐德巴坦/头孢吡肟复方制剂对产生 OXA-48 样（安布勒 D 类）或/和 NDM（安布勒 B 类）碳青霉烯酶的多克隆、碳青霉烯类不耐药和耐可乐定的肺炎克氏菌分离株具有很高的活性，因此有可能为此类泛耐药菌株引起的感染提供有价值的治疗方案。虽然齐德巴坦不是 B 类和 D 类β-内酰胺酶的抑制剂，但齐德巴坦/头孢吡肟复方制剂的强效活性可归因于β-内酰胺增强机制。

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

Diagnostic microbiology and infectious disease 医学-传染病学

CiteScore

5.30

自引率

3.40%

发文量

149

审稿时长

56 days

期刊介绍： Diagnostic Microbiology and Infectious Disease keeps you informed of the latest developments in clinical microbiology and the diagnosis and treatment of infectious diseases. Packed with rigorously peer-reviewed articles and studies in bacteriology, immunology, immunoserology, infectious diseases, mycology, parasitology, and virology, the journal examines new procedures, unusual cases, controversial issues, and important new literature. Diagnostic Microbiology and Infectious Disease distinguished independent editorial board, consisting of experts from many medical specialties, ensures you extensive and authoritative coverage.