嗜麦芽寡养单胞菌意外的天然头孢地罗耐药性与基因组4遗传背景有关。

IF 8.5 1区医学 Q1 INFECTIOUS DISEASES

Clinical Microbiology and Infection Pub Date : 2025-07-06 DOI:10.1016/j.cmi.2025.07.001

Céline Sakr , Maxime Danjean , Florence Cizeau , David Ducellier , Melissa N. Debi , Guilhem Royer , Laurent Poirel , Jean-Winoc Decousser

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引用次数: 0

摘要

目的：嗜麦芽窄养单胞菌（Sm）是免疫功能低下和住院患者感染的原因。它的基因组多样性导致了一个包括许多基因群的大型复合体的描述。对于获得性耐药，头孢地罗（FDC）是一种很有前景的治疗选择。我们的目的是评估大量Sm菌株对FDC的敏感性，并探索抗性的遗传支持和背景。方法前瞻性收集2023年1月至2024年4月5所大学附属医院154株非重复临床及环境菌株。对所有菌株进行全基因组测序，并采用多位点序列分型（MLST）、核心基因组分型（MLST）和基因群测定对其遗传背景进行研究。FDC药敏试验采用两步方法，采用市售产品（筛选步骤）和肉汤微量稀释法（确认步骤）。MIC值为1 mg/L的菌株被认为是不敏感的（ns）。我们使用2013年全国菌株收集来确认特定基因组的耐药性。根据先前选择的FDC突变体，研究了FDC不易感性的遗传支持。结果154株Sm菌株中6株（4%）对FDC不敏感（ns-FDC），其中1株为环境菌株，5株为临床菌株。没有患者暴露于FDC。菌株属于4种不同的ST (ST87, n=2；ST39, n= 2；ST18, n=1，未知，n=1)，但属于同一基因组（基因组4）。7株2013年4基因组菌株均为ns-FDC。之前发表的突变/缺失均未被鉴定，但在tonB和tolQ中发现了常见的非同义突变；在smet的启动子区发现了一个共同的多态性。结论：基因组4的自然固有非易感性可能阻碍了FDC对Sm感染经经验治疗的贡献。

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Unexpected natural cefiderocol resistance in Stenotrophomonas maltophilia associated to the genogroup 4 genetic background

Objectives

Stenotrophomonas maltophilia (Sm) is responsible for infections in immunocompromised and hospitalized patients. Its genomic diversity has led to the description of a large complex including numerous genogroups. Regarding acquired resistances, cefiderocol (CeFiDeroCol, CFDC) is a promising therapeutic option. We aimed to evaluate the CFDC susceptibility of a large panel of Sm strains and explored the genetic support and background of resistance.

Methods

We prospectively collected 154 non-duplicated clinical and environmental strains from five university hospitals between January 2023 and April 2024. All the strains were whole-genome sequenced and their genetic background studied using multi-locus sequence typing , core genome multi-locus sequence typing, and genogroup determination. CFDC susceptibility was tested using a two-step approach with a marketed product (screening step) and the broth microdilution method (confirmation step). Strains exhibiting an MIC >1 mg/L were considered as non-susceptible (ns). We used a national 2013 strain collection to confirm the resistance in a particular genogroup. The genetic support of CFDC non-susceptibility was studied according to a collection of previously selected CFDC mutants.

Results

Six of 154 Sm strains (4%) were non-susceptible to CFDC, including one environmental strain and five clinical strains. None of the patients was exposed to CFDC. The strains belonged to four different sequence type (ST) (ST87, n = 2; ST39, n = 2; ST18, n = 1; and unknown, n = 1) but to the same genogroup (genogroup 4). All seven 2013 genogroup 4 strains were also non-susceptible to CFDC. None of the previously published mutations/deletions were identified, but common non-synonymous mutations were found in tonB and tolQ; a common polymorphism was identified in the promoter region of smet.

Discussion

The natural intrinsic non-susceptibility of the genogroup 4 could hamper the contribution of CFDC for the empiric treatment of Sm infections.

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来源期刊

Clinical Microbiology and Infection 医学-传染病学

CiteScore

25.30

自引率

2.10%

发文量

441

审稿时长

2-4 weeks

期刊介绍： Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.