Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study
Abstract
BACKGROUND: Rising antimicrobial resistance of Helicobacter pylori is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in H pylori and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin.
METHODS: In this retrospective phenotypic and genotypic observational study, we included 1011 H pylori whole-genome sequences and strains of known geographical origin from the H pylori Genome Project (HpGP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 HpGP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify 23S rRNA and gyrA variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, 23S rRNA 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, gyrA A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype-phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete HpGP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the HpGP…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 1,779 participants or records.
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