Unexpected natural cefiderocol resistance in Stenotrophomonas maltophiliaassociated to the genogroup 4 genetic background.

IF 10.9 1区 医学 Q1 INFECTIOUS DISEASES
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

Abstract

Objectives: Stenotrophomonas maltophilia (Sm) is responsible for infections among immunocompromised and hospitalized patients. Its genomic diversity led to the description of a large complex including numerous genogroups. Regarding acquired resistances, cefiderocol (FDC) is a promising therapeutic option. We aimed to evaluate the the FDC 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 (MLST), core genome MLST and genogroup determination. FDC susceptibility was tested using a two steps approach using a marketed product (screening step) and the broth microdilution method (confirmation step). Strains exhibited a MIC > 1 mg/L were considered as non-susceptible (ns). We used a national 2013 strains collection to confirm the resistance of a particular genogroup. The genetic support of FDC non-susceptibility was studied according to a collection of previously selected FDC mutants.

Results: Six out of 154 Sm strains (4%) were non-susceptible to FDC (ns-FDC), including one environmental and five clinical strains. None of the patients was exposed to FDC. The strains belonged to four different ST (ST87, n=2; ST39, n= 2; ST18, n=1, unknown, n=1) but to the same genogroup (genogroup 4). All the seven 2013 genogroup 4 strains were also ns-FDC. 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.

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

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。
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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来源期刊
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.
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