OXA-carbapenemases and mutations within PBPs in ST2 carbapenem-resistant A. baumannii: Evaluating the efficacy of cefiderocol and ampicillin-sulbactam combination therapy

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-06-27 DOI:10.1016/j.jgar.2025.06.014

Carlo Tascini , Simone Giuliano , Luca Martini , Novella Carannante , Bernardo Mariano , Mariagrazia Perilli , Alessandra Piccirilli

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引用次数: 0

Abstract

Objectives

Carbapenem-resistant Acinetobacter baumannii (A. baumannii; CRAB) isolates represent a serious public health concern. Recently, a novel molecule, the cefiderocol (FDC), has emerged as a promising therapeutic option for CRAB infections. In the present study, we analysed the genomes of five A. baumannii ST2 isolates from four hospitalized patients. All patients were treated with FDC and an ampicillin/sulbactam (AMP/SUL) combination.

Methods

Whole-genome sequencing of the five CRAB isolates was performed using an Illumina MiSeq instrument. A detailed bioinformatic analysis was carried out to acquire information about genotyping, antimicrobial resistance genes (ARGs), virulence associated genes (VAGs), single nucleotide polymorphisms (SNPs), and the phylogenetic tree of the five CRAB isolates.

Results

Among the five CRAB isolates, only three (Ab.2, Ab.3, and Ab.4) exhibited resistance to FDC. The genomes of all isolates were highly similar, and multilocus sequence typing (MLST) analysis indicated they all belong to sequence type 2 (ST2), corresponding to international clone 2. Phylogenetic analysis suggests that isolates Ab.2, Ab.3, and Ab.4 may share a common ancestor or be linked by a possible transmission event. In contrast, isolates Ab.1 and Ab.5 were more divergent from the other three. Nevertheless, all five isolates harboured the same ARGs and VAGs. The OXA-23, OXA-66, and ADC-25 β-lactamases were detected in all strains. The FDC-non-susceptible isolates showed a K235N/H370Y double mutation within PBP3, along with a G370C substitution in PBP1a.

Conclusions

The four clinical cases described in this study represent an important example of the efficacy and good practice of FDC plus AMP/SUL combination in the treatment of critical patients suffering from CRAB infections. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

查看原文本刊更多论文

oxa -碳青霉烯酶和ST2耐碳青霉烯类鲍曼不动杆菌PBPs突变：评价头孢地罗和氨苄西林-舒巴坦联合治疗的疗效。

目的：耐碳青霉烯类鲍曼不动杆菌（CRAB）分离株引起了严重的公共卫生问题。最近，一种新型分子头孢地罗（cefiderocol， FDC）被认为是治疗螃蟹感染的有希望的选择。在本研究中，我们分析了从4名住院患者分离的5株鲍曼不动杆菌ST2的基因组。所有患者均接受FDC和氨苄西林/舒巴坦（AMP/SUL）联合治疗。方法：采用Illumina MiSeq仪器对5株CRAB分离株进行全基因组测序。通过详细的生物信息学分析，获得5株螃蟹的基因分型、耐药基因（ARGs）、毒力相关基因（VAGs）、单核苷酸多态性（snp）和系统发育树等信息。结果：5株CRAB分离株中，仅有3株（Ab.2、Ab.3和Ab.4）对FDC产生抗性。所有分离株的基因组高度相似，MLST分析表明它们均属于序列2型（ST2），与国际克隆2对应。系统发育分析表明，分离株Ab.2、Ab.3和Ab.4可能有共同的祖先，或通过可能的传播事件联系在一起。而分离株Ab.1和Ab.5与其他3株差异较大。然而，所有5个分离株都含有相同的arg和VAGs。所有菌株均检测到OXA-23、OXA-66和ADC-25 β-内酰胺酶。fdc非敏感株PBP3出现K235N/H370Y双突变，PBP1a出现G370C置换。结论：本研究描述的4例临床病例代表了FDC联合AMP/SUL治疗危重患者螃蟹感染的疗效和良好实践的重要例子。

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 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.