Impact of amoxicillin resistance on the efficacy of amoxicillin-containing regimens for Helicobacter pylori eradication: analysis of five randomized trials.

BACKGROUND: The impact of amoxicillin resistance on the efficacy of regimens containing amoxicillin for Helicobacter pylori eradication remains unknown. OBJECTIVES: To investigate whether the efficacy of an amoxicillin-containing regimen is affected by amoxicillin resistance and to identify the optimal breakpoint for amoxicillin resistance. METHODS: This was a pooled analysis of five randomized trials conducted in Taiwan from 2007 to 2016. Patients who received amoxicillin-containing regimens were recruited. MICs were determined by agar dilution testing. Meta-analysis was performed to assess the risk ratio of eradication failure in amoxicillin-resistant strains compared with susceptible strains of seven different regimens. We performed further the pooled analysis and logistic regression in patients treated with clarithromycin triple therapy to identify the optimal breakpoint for amoxicillin resistance. RESULTS: A total of 2339 patients with available amoxicillin MICs were enrolled. Meta-analysis showed that the presence of amoxicillin resistance was consistently associated with increased risk of treatment failure of amoxicillin-containing regimens at different breakpoints (risk ratio: 1.41, 95% CI 1.12-1.78, P = 0.004 when the cut-off was 0.5 mg/L). The heterogeneity was low (I2 = 0%, P = 0.615). Pooled analysis also showed that amoxicillin resistance was an independent risk factor for treatment failure of clarithromycin triple therapy at different breakpoints. The best correlation was observed when the breakpoint of amoxicillin resistance was ≥0.125 mg/L (kappa coefficient 0.298), at which the resistance rate was 11.1% (110 of 990). CONCLUSIONS: The efficacies of amoxicillin-containing regimens are affected by amoxicillin resistance and the optimal breakpoint MIC is ≥ 0.125 mg/L.