Molecular Detection of Clarithromycin Resistance in Gastric Biopsies and Stool Samples from Patients with Helicobacter pylori Infection: A Review

Abstract

Clarithromycin resistance is the single strongest predictor of eradication failure in Helicobacter pylori infection, and the conventional way of measuring it, culture with phenotypic susceptibility testing, requires endoscopy and often fails to grow the organism at all. Molecular detection of the responsible point mutations avoids both problems, and can be done on stool. Objectives: To review the published evidence on molecular detection of clarithromycin resistance in Helicobacter pylori: which mutations are targeted
and how often each occurs, how molecular testing on gastric biopsies compares with culture, how stool-based testing performs against biopsy-derived reference standards, and what susceptibility-guided treatment achieves. Material and Methods: Narrative review of diagnostic accuracy studies, assay evaluations, meta-analyses, consensus reports and guidelines indexed in PubMed and the major gastroenterology and clinical microbiology journals. Studies were eligible if they reported the prevalence or distribution of
resistance-conferring mutations, the performance of a molecular assay against culture or sequencing, the accuracy of stool-based testing, or treatment outcomes stratified by resistance. No new patient data were generated; every frequency and accuracy estimate quoted is one published by the original investigators. Results: Pooled across World Health Organization regions, primary and secondary clarithromycin resistance exceeded 15 per cent in all regions except the Americas and South-East Asia, and resistance was strongly associated with failure of clarithromycin-containing regimens, with an odds ratio of 6.97 (95% CI 5.23-9.28). In a prospective study of 1,200 patients, 23S rRNA mutations were found in 17.5 per cent of PCR-positive gastric biopsies, distributed as A2143G in 71.4 per cent, A2142G in 25 per cent and A2142C in 3.6 per cent; mixed susceptible and resistant infections were present in 1.9 per cent
and were invisible to phenotypic testing. Pooling stool studies, PCR for clarithromycin resistance gave a sensitivity of 0.91 and a specificity of 0.97, with an area under the curve of 0.94. Conclusion: Molecular testing detects resistance more reliably than culture, identifies mixed infections that phenotypic testing misses, and works on stool at accuracy adequate for clinical use. Its principal limitation is what it cannot see: it reports the mutations it is designed to detect and nothing else, so a negative molecular result excludes the common mechanisms rather than excluding resistance. Abbreviations: H. pylori – Helicobacter pylori, CLR – Clarithromycin, MIC – Minimum Inhibitory Concentration, PCR – Polymerase Chain Reaction, RT-PCR – Real-Time Polymerase Chain Reaction, FRET – Fluorescence Resonance Energy Transfer, FISH – Fluorescence In Situ Hybridisation, rRNA – Ribosomal Ribonucleic Acid, WHO – World Health Organization, PPI – Proton Pump Inhibitor, OR – Odds Ratio, AUC – Area Under the Curve, FFPE – Formalin-Fixed Paraffin-Embedded.