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Objectives  The antimicrobial resistance of  Helicobacter pylori  ( H. pylori ) in most countries and regions has increased significantly. It has not been fully confirmed whether the detection of  H. pylori  resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical personalized treatment. The objective of this study was to assess and compare the efficacy of different antimicrobial resistance-guided quadruple therapies in refractory  H. pylori -infected individuals who had undergone unsuccessful prior eradication treatments.    Methods  From January 2019 to February 2020, genotypic and phenotypic resistances were determined by polymerase chain reaction (PCR), whole genome sequencing (WGS) and broth microdilution test, respectively, in 39  H. pylori -infected patients who have failed eradication for at least twice. The patients were retreated with bismuth quadruple therapy for 14 days according to individual antibiotic resistance results. Eradication status was determined by the  13 C-urea breath test.    Results  The overall eradication rate was 79.5% (31/39, 95% CI 64.2–89.5%) in the intention-to-treat (ITT) analysis and 88.6% (31/35, 95% CI 73.5–96.1%) in the per- protocol analysis (PP) analysis. The presence of amoxicillin resistance (OR, 15.60; 95% CI, 1.34–182.09;  p  = 0.028), female sex (OR, 12.50; 95% CI, 1.10–142.31;  p  = 0.042) and no less than 3 prior eradication treatments (OR, 20.25; 95% CI, 1.67–245.44;  p  = 0.018), but not the methods for guiding therapy ( p  &amp;gt; 0.05) were associated with treatment failure. Resistance-guided therapy achieved eradication rates of more than 80% in these patients. The eradication rate of  H. pylori  in the phenotypic resistance-guided group was correlated well with genotype resistance-guided groups, including PCR and WGS.    Conclusion  Culture or molecular method guiding therapy can enable personalized, promise salvage treatments, and achieve comparably high eradication rates in patients with refractory  H. pylori  infection. The detection of  H. pylori  resistance mutations has a good clinical application prospect.    Protocol Study Register  [ clinicaltrials.gov ], identifier [ChiCTR1800020009].

frontiers in microbiology

Correlation Analysis Among Genotype Resistance, Phenotype Resistance, and Eradication Effect After Resistance-Guided Quadruple Therapies in Refractory Helicobacter pylori Infections