Bismuth-containing quadruple therapy for Helicobacter pylori: lessons from China

Abstract

Antimicrobial resistance has continued to undermine many popular anti-Helicobacter pylori therapies. Antibiotic resistance to commonly used anti-H. pylori drugs in China has increased markedly, making China an ideal site to identify regimens that remain effective despite widespread antimicrobial resistance. Bismuth is one of the few antimicrobials to which resistance does not develop. Factors contributing to H. pylori treatment success include host factors (e.g., genetic differences in the metabolism of the drugs used), bacterial factors (e.g., susceptibility), and details of the regimen (e.g., doses, dosing interval, dosing in relation to meals, formulation, etc.). We reviewed the recent experience in China with bismuth-containing quadruple therapies. The experience consists of 16 studies with 25 arms involving 1971 patients to identify successful regimens (defined as reliably obtaining 90% or greater eradication per protocol) deserving further study. Despite high rates of resistance to commonly used antimicrobials, several regimens could achieve high success. These were characteristically 14-day regimens containing a proton pump inhibitor and either tetracycline and metronidazole or furazolidone and amoxicillin. We propose approaches for further development including for optimization and simplification related to convenience and side effects (e.g., twice rather than three or four times daily or administration at the noon and evening meal instead of at breakfast and evening) while maintaining effectiveness of at least 90%. Studies in China identified regimens that were highly effective despite the high prevalence of resistance to metronidazole, fluoroquinolones, and macrolides. Multicenter randomized studies will be required to confirm which is the best.

Conflict of interest statement

Conflicts of interest: Dr. Graham is a unpaid consultant for Novartis in relation to vaccine development for treatment or prevention of H. pylori infection. Dr. Graham is a also a paid consultant for RedHill Biopharma regarding novel H. pylori therapies and for Otsuka Pharmaceuticals regarding diagnostic breath testing. Dr. Graham has received royalties from Baylor College of Medicine patents covering materials related to 13C-urea breath test. Drs Lu and Zhang have no conflicts.