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支气管扩张症患者的慢性感染:产碳青霉烯酶流行高风险克隆株的隐匿储存库。

chronic infections in patients with bronchiectasis: a silent reservoir of carbapenemase-producing epidemic high-risk clones.

作者信息

Muñoz-Santa Alba, López-Causapé Carla, Bellés Alba, Gómez-Arbonés Xavier, Cortés-Lara Sara, García-González Mercè, Pifarré-Teixidó Ricardo, Oliver Antonio

机构信息

Servicio de Análisis Clínicos, Hospital Universitari Arnau de Vilanova de Lleida, Institut de Recerca Biomèdica de Lleida (IRB Lleida), Universitat de Lleida, Lleida, Spain.

Servicio de Microbiología, Hospital Univeristario Son Espases, Instituto de Investigación Sanitaria Illes Balears, CIBERINFEC, Palma de Mallorca, Spain.

出版信息

JAC Antimicrob Resist. 2025 Apr 8;7(2):dlaf053. doi: 10.1093/jacamr/dlaf053. eCollection 2025 Apr.


DOI:10.1093/jacamr/dlaf053
PMID:40201539
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11976719/
Abstract

OBJECTIVES: is one of the major drivers of morbidity and mortality in patients with chronic underlying diseases. Whereas cystic fibrosis (CF) strains have been well studied, non-CF bronchiectasis isolates have received less scientific attention. METHODS: We determined the antibiotic susceptibility profiles of a collection of 100 isolates recovered from a total of 100 non-CF bronchiectasis patients attending a Catalonian hospital. All carbapenemase-producing isolates were characterized by WGS. RESULTS: Twelve isolates were classified as MDR (12%) and six were found to be carbapenemase (VIM-2) producers (6%). Of note, two of the VIM-2-producing isolates were carbapenem susceptible due to the presence of inactivating mutations in MexAB-OprM efflux pump components. These isolates exhibited properties of chronic isolates, such as mutator or mucoid phenotypes that are associated with persistent infections despite intensive antibiotic therapies. The phylogenetic analysis evidenced that all VIM-2 isolates belonged to the high-risk clone ST235. Core-genome MLST analysis revealed 7-260 allelic differences, arguing against recent transmission but a common source of infection or an ancient interpatient transmission event could not be ruled out. CONCLUSIONS: Altogether, these findings suggest that chronic respiratory infections can be an important and silent reservoir of transferable resistance determinants and high-risk clones, thus contributing to their increased resistance and worldwide dissemination.

摘要

目的:是慢性基础疾病患者发病和死亡的主要驱动因素之一。虽然囊性纤维化(CF)菌株已得到充分研究,但非CF支气管扩张分离株受到的科学关注较少。 方法:我们确定了从一家加泰罗尼亚医院的100例非CF支气管扩张患者中分离出的100株菌株的抗生素敏感性谱。所有产碳青霉烯酶的分离株均通过全基因组测序(WGS)进行鉴定。 结果:12株分离株被归类为多重耐药(MDR,12%),6株被发现是碳青霉烯酶(VIM-2)产生菌(6%)。值得注意的是,由于MexAB-OprM外排泵组件中存在失活突变,两株产VIM-2的分离株对碳青霉烯类药物敏感。这些分离株表现出慢性分离株的特性,如突变体或黏液样表型,这些表型与尽管进行了强化抗生素治疗仍持续存在的感染有关。系统发育分析表明,所有产VIM-2的分离株均属于高风险克隆ST235。核心基因组多位点序列分型(MLST)分析显示有7 - 260个等位基因差异,这表明不太可能是近期传播,但不能排除共同感染源或古老的患者间传播事件。 结论:总之,这些发现表明慢性呼吸道感染可能是可转移耐药决定因素和高风险克隆的重要且隐匿的储存库,从而导致其耐药性增加并在全球传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272e/11976719/7781f752f6b0/dlaf053f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272e/11976719/7781f752f6b0/dlaf053f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272e/11976719/7781f752f6b0/dlaf053f1.jpg

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本文引用的文献

[1]
Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group.

Clin Microbiol Infect. 2024-4

[2]
Hypermutator strains of Pseudomonas aeruginosa reveal novel pathways of resistance to combinations of cephalosporin antibiotics and beta-lactamase inhibitors.

PLoS Biol. 2022-11

[3]
Comparative analysis of in vitro dynamics and mechanisms of ceftolozane/tazobactam and imipenem/relebactam resistance development in Pseudomonas aeruginosa XDR high-risk clones.

J Antimicrob Chemother. 2022-3-31

[4]
Selection of AmpC β-Lactamase Variants and Metallo-β-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.

Antimicrob Agents Chemother. 2022-2-15

[5]
Predicting Pseudomonas aeruginosa susceptibility phenotypes from whole genome sequence resistome analysis.

Clin Microbiol Infect. 2021-11

[6]
Impact of Infection on Patients with Chronic Inflammatory Airway Diseases.

J Clin Med. 2020-11-24

[7]
Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases: 2020 update.

Int J Antimicrob Agents. 2020-12

[8]
Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa.

Commun Biol. 2020-8-3

[9]
In vitro dynamics and mechanisms of resistance development to imipenem and imipenem/relebactam in Pseudomonas aeruginosa.

J Antimicrob Chemother. 2020-9-1

[10]
Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections.

Clin Microbiol Rev. 2019-8-28

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