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乌克兰冲突创伤相关广泛耐药革兰阴性菌严重感染中不断演变的抗菌药物耐药性:一项观察性研究

Evolving antimicrobial resistance of extensively drug-resistant Gram-negative severe infections associated with conflict wounds in Ukraine: an observational study.

作者信息

Pallett Scott J C, Morkowska Anna, Woolley Stephen D, Potochilova Viktoria V, Rudnieva Kateryna L, Iungin Olga S, Sgro Vincenzo, Boyd Sara E, Reece Nicola, Lambert Zoe L, Tan Ngee Keong, Mughal Nabeela, Moshynets Olena V, Moore Luke S P, O'Shea Matthew K

机构信息

Clinical Infection Department, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Centre of Defence Pathology, Royal Centre for Defence Medicine, Queen Elizabeth Hospital, Birmingham, UK.

出版信息

Lancet Reg Health Eur. 2025 Mar 20;52:101274. doi: 10.1016/j.lanepe.2025.101274. eCollection 2025 May.

Abstract

BACKGROUND

Conflict can have devastating effects on the development and spread of antimicrobial resistance. In Ukraine, early data post-injury are limited. We aim to explore extensively drug-resistant (XDR) Gram negative phenotypes and genotypes for infections arising early following conflict-associated wounds in Ukraine.

METHODS

Carbapenem-resistant infections following conflict-associated wounds in Ukraine (February-May 2024) underwent extended antimicrobial susceptibility testing (AST) for 19 antimicrobial agents using 2025 European Committee for Antimicrobial Susceptibility Testing breakpoints. Carbapenemase genes were identified using a novel multiplex molecular resistance assay. Infections arising in the first seven days versus those arising after seven days since injury were compared by logistic regression. Significance was set at  < 0.05.

FINDINGS

100 isolates were tested (53, 53.0% ; 16, 16.0% Enterobacterales; 18, 18.0% and 13; 13.0% ). Gentamicin ( = 0.0046) and colistin ( = 0.049) resistance were higher in infections arising later. Overall, resistance rates for amikacin (74/100, 74.0%), cefiderocol (44/100, 44.0%) and ceftazidime-avibactam (26/79, 67.1%) were observed. Prevalent resistance genes included NDM + OXA-48-like (24/100, 24.0%), NDM-only (24/100, 24.0%) and KPC (9/100, 9%). Others included OXA 23-like/51-like, IMP and/or mcr1. Earlier infection isolates had a higher burden of carbapenemases/isolate ( = 0.006).

INTERPRETATION

Extensively drug-resistant infections were observed early post-injury in Ukraine, with some trend to further resistance in those arising later in the patient pathway. A diverse presence of carbapenemase genes amid XDR Gram negative phenotypes highlights the importance of early screening for mechanisms of resistance in this setting.

FUNDING

This study was funded by the Healthcare Infection Society and CW+ Charity.

摘要

背景

冲突对抗菌药物耐药性的发展和传播可能产生毁灭性影响。在乌克兰,受伤后的早期数据有限。我们旨在广泛探索乌克兰冲突相关伤口后早期感染的广泛耐药(XDR)革兰氏阴性菌表型和基因型。

方法

对乌克兰2024年2月至5月冲突相关伤口后的碳青霉烯耐药感染,使用2025年欧洲抗菌药物敏感性试验委员会的断点,对19种抗菌药物进行了扩展抗菌药物敏感性试验(AST)。使用一种新型多重分子耐药检测法鉴定碳青霉烯酶基因。通过逻辑回归比较受伤后前七天与七天后发生的感染。显著性设定为<0.05。

研究结果

共检测了100株分离株(53株,53.0%;16株,16.0%肠杆菌科细菌;18株,18.0% ,13株,13.0%)。庆大霉素(=0.0046)和黏菌素(=0.049)在后期发生的感染中耐药性更高。总体而言,观察到阿米卡星(74/100,74.0%)、头孢地尔(44/100,44.0%)和头孢他啶-阿维巴坦(26/79,67.1%)的耐药率。常见的耐药基因包括NDM+OXA-48样(24/100,24.0%)、仅NDM(24/100,24.0%)和KPC(9/100,9%)。其他包括OXA 23样/51样、IMP和/或mcr1。早期感染分离株的碳青霉烯酶/分离株负担更高(=0.006)。

解读

在乌克兰受伤后早期观察到广泛耐药感染,在患者病程后期发生的感染有进一步耐药的趋势。在XDR革兰氏阴性菌表型中多种碳青霉烯酶基因的存在凸显了在这种情况下早期筛查耐药机制的重要性。

资助

本研究由医疗保健感染协会和CW+慈善机构资助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c22/11987627/477e26df4a1e/gr1.jpg

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