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产超广谱β-内酰胺酶肠杆菌科在马拉维成年人肠道中的定殖动态。

Colonization dynamics of extended-spectrum beta-lactamase-producing Enterobacterales in the gut of Malawian adults.

机构信息

Malawi-Liverpool Wellcome Clinical Research Programme, Blantyre, Malawi.

Liverpool School of Tropical Medicine, Liverpool, UK.

出版信息

Nat Microbiol. 2022 Oct;7(10):1593-1604. doi: 10.1038/s41564-022-01216-7. Epub 2022 Sep 5.

DOI:10.1038/s41564-022-01216-7
PMID:36065064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9519460/
Abstract

Drug-resistant bacteria of the order Enterobacterales which produce extended-spectrum beta-lactamase enzymes (ESBL-Enterobacterales, ESBL-E) are global priority pathogens. Antimicrobial stewardship interventions proposed to curb their spread include shorter courses of antimicrobials to reduce selection pressure but individual-level acquisition and selection dynamics are poorly understood. We sampled stool of 425 adults (aged 16-76 years) in Blantyre, Malawi, over 6 months and used multistate modelling and whole-genome sequencing to understand colonization dynamics of ESBL-E. Models suggest a prolonged effect of antimicrobials such that truncating an antimicrobial course at 2 days has a limited effect in reducing colonization. Genomic analysis shows largely indistinguishable diversity of healthcare-associated and community-acquired isolates, hence some apparent acquisition of ESBL-E during hospitalization may instead represent selection from a patient's microbiota by antimicrobial exposure. Our approach could help guide stewardship protocols; interventions that aim to review and truncate courses of unneeded antimicrobials may be of limited use in preventing ESBL-E colonization.

摘要

产超广谱β-内酰胺酶（ESBL-肠杆菌科，ESBL-E）的耐药物菌属于全球优先病原体。为了抑制其传播，提出了抗菌药物管理干预措施，包括缩短抗菌药物疗程以降低选择压力，但个体水平的获得和选择动态还了解甚少。我们在马拉维布兰太尔采集了 425 名年龄在 16-76 岁的成年人的粪便样本，历时 6 个月，并使用多状态模型和全基因组测序来了解 ESBL-E 的定植动态。模型表明，抗菌药物的作用时间较长，因此将抗菌药物疗程缩短至 2 天，对减少定植的效果有限。基因组分析表明，与医疗保健相关的和社区获得性分离株的多样性基本相同，因此，住院期间 ESBL-E 的一些明显获得可能是抗生素暴露对患者微生物群的选择所致。我们的方法可以帮助指导管理方案；旨在审查和缩短不必要的抗菌药物疗程的干预措施，可能在预防 ESBL-E 定植方面效果有限。

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