Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data

作者：Francesc Coll, Theodore Gouliouris, Beth Blane, Corin Yeats, Kathy E. Raven, Catherine Ludden, Fahad Khokhar, Hayley J. Wilson, Leah Wendy Roberts, Ewan M. Harrison, Carolyne Horner, Thi Hoi Le, Thi Hoa Nguyen, Vu Trung Nguyen, Nicholas M Brown, Mark A. Holmes, Julian Parkhill, Mili Estee Török, Sharon J. Peacock · 发表于：The Lancet Microbe · 年份：2024 · DOI：10.1016/s2666-5247(23)00297-5 · 被引用次数：46 · 研究领域：Antimicrobial Resistance in Staphylococcus、Bacterial Identification and Susceptibility Testing、Clostridium difficile and Clostridium perfringens research

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, a...