In vitro activity of cefiderocol against carbapenemase-producing and meropenem-non-susceptible Gram-negative bacteria collected in the Japan Antimicrobial Resistant Bacterial Surveillance

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES
Shizuo Kayama, Sayoko Kawakami, Kohei Kondo, Norikazu Kitamura, Liansheng Yu, Wataru Hayashi, Koji Yahara, Yo Sugawara, Motoyuki Sugai
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引用次数: 0

Abstract

Objectives

The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against these pathogens. Several studies have reported the in vitro activity of CFDC against isolates from Europe, the United States, and China, but the activity against carbapenem-resistant bacteria with IMP-type carbapenemase has not been extensively studied. We, therefore, studied the in vitro activities of CFDC against carbapenem-resistant bacteria with available genomic backgrounds based on whole-genome sequencing (WGS) in Japan, where the IMP-type is the predominant carbapenemase produced by Gram-negative rods.

Methods

We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from a collection of Gram-negative clinical isolates collected during a Japan Antimicrobial Resistance Bacterial Surveillance program and evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-non-susceptible Enterobacterales, and carbapenemase-producing nonfermentative bacteria.

Results

Among these, 97.7% of carbapenemase-producing Enterobacterales (99.2% of IMP-type carbapenemase-producing Enterobacterales), 100% of carbapenemase-producing P. aeruginosa, and 91.2% of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. CFDC was highly effective against class A-, B-, and D β-lactamase-harbouring isolates when compared to the other antimicrobial agents. In addition, the relationship between CFDC resistance and three genetic factors involved in resistance was discussed.

Conclusions

This is the first large-scale study to systematically demonstrate the efficacy of CFDC against IMP-type carbapenemase-producing strains with known genomic backgrounds.

Abstract Image

头孢哌酮对日本抗菌素耐药性细菌监测中收集的产碳青霉烯酶和美罗培南不敏感革兰氏阴性菌的体外活性。
目的:对于由具有多重耐药性的革兰氏阴性病原体引起的感染,可供选择的治疗方案往往十分有限。头孢克洛(CFDC)是一种新型嗜苷头孢菌素,对这些病原体具有活性。已有多项研究报道了 CFDC 对来自欧洲、美国和中国的分离菌的体外活性,但对具有 IMP 型碳青霉烯酶的碳青霉烯耐药菌的活性尚未进行广泛研究。因此,我们根据日本的全基因组测序(WGS)结果,研究了 CFDC 对具有可用基因组背景的耐碳青霉烯细菌的体外活性,在日本,IMP 型碳青霉烯酶是革兰氏阴性杆菌产生的主要碳青霉烯酶:方法:我们从收集的革兰氏阴性杆菌中选取了 603 个分离株(528 个肠杆菌属、18 个铜绿假单胞菌属和 57 个醋杆菌属)。方法:我们从日本抗菌药耐药性细菌监测计划收集的革兰氏阴性临床分离株中挑选了 603 株分离株(528 株肠杆菌属、18 株铜绿假单胞菌属和 57 株不动杆菌属),并评估了 CFDC、头孢妥赞/他唑巴坦(CTLZ/TAZ)、亚胺培南-雷贝拉菌(CTLZ/TAZ)和头孢妥赞/他唑巴坦(CTLZ/TAZ)的抗菌活性、亚胺培南-雷巴坦(IPM/REL)和头孢唑肟/阿维巴坦(CAZ/AVI)对产生碳青霉烯酶的肠杆菌科细菌、不产生碳青霉烯酶的美罗培南不敏感肠杆菌科细菌和产生碳青霉烯酶的非发酵菌的抗菌活性进行了评估。结果显示其中,97.7%的产碳青霉烯酶肠杆菌(99.2%的 IMP 型产碳青霉烯酶肠杆菌)、100%的产碳青霉烯酶铜绿假单胞菌和 91.2%的产碳青霉烯酶醋酸杆菌对 CFDC 易感,显示出比本研究评估的其他抗菌剂更好的抗菌活性。与其他抗菌剂相比,CFDC 对 A 类、B 类和 D 类 β-内酰胺酶耐药分离菌具有很高的疗效。此外,还讨论了 CFDC 耐药性与耐药性涉及的三个遗传因素之间的关系:这是首次系统性证明 CFDC 对已知基因组背景的 IMP 型碳青霉烯酶产菌株有效的大规模研究。
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
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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