Randomized comparison of two non-bismuth-containing second-line rescue therapies for Helicobacter pylori

Background: Classical second-line anti-Helicobacter pylori includes proton-pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin-containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second-line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second-line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. Materials and methods: One hundred and twenty-eight patients who failed H. pylori eradication using the standard triple therapy for 7days are randomly assigned to either EAL group (esomeprazole 40mg twice daily, amoxicillin 1g twice daily, and levofloxacin 500mg once daily) for 7days or EAT group (esomeprazole 40mg twice daily, amoxicillin 1g twice daily, tetracycline 500mg four times daily) for 14days. Follow-up endoscopy or urea breath test was performed 8weeks later to assess treatment response. Results: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p=.676 (in intention-to-treat analysis) and 80.3 versus 80%, p=.0964 (per-protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p=.952) but more adverse events in the EAT group (6.3 vs 12.5%, p=.225). Conclusions: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14-day EAT regimens attained an unacceptable report card of 75% eradication rates in intention-to-treat analysis and was not even superior to the 7-day EAL regimen. Drug-drug interaction between combined antibiotics should be considered other than in vivo drug resistances.