Which regimen is best for antibiotic-resistant H pylori?

In regions where there is high antibiotic resistance of Helicobacter pylori (H pylori), the best options in treatment-naïve patients include the 3-in-1 single capsule, bismuth quadruple therapy, and concomitant regimen with tinidazole, suggests a study. In non-naïve patients, the 3-in-1 single capsule and the triple therapy with levofloxacin offers adequate eradication.

“Other first-line alternatives were quadruple therapies with clarithromycin-amoxicillin-tinidazole or clarithromycin-amoxicillin-bismuth,” said the researchers, led by Luis Bujanda, Department of Gastroenterology, Biodonostia Health Research Institute, San Sebastián, Spain. “In addition, in second-line therapy, the triple therapy with amoxicillin-levofloxacin might be also an option.”

Bujanda and his team conducted this prospective, multicentre, international registry on the management of H pylori, and assessed all infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021.

Of the 2,852 treatment-naïve patients with analysed culture results, 22 percent had resistance to clarithromycin, 27 percent to metronidazole, and 18 percent to quinolones. [Am J Gastroenterol 2024;119:646-654]

Regardless of resistance, the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91 percent) and the quadruple with bismuth were the most effective, achieving good eradication rates even in the presence of bacterial resistance to clarithromycin or metronidazole.

Additionally, concomitant treatment with tinidazole achieved a 99-percent (90/91) eradication rate relative to 84 percent (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole fell short of attaining optimal results.

In 1,118 non-naïve patients analysed, 49 percent were resistant to clarithromycin, 41 percent to metronidazole, and 24 percent to quinolones. Only the 3-in-1 single capsule and the triple therapy with levofloxacin showed acceptable eradications rates at 87 percent and 85 percent, respectively.

Triple therapy

The per-protocol analysis of a previous study on H pylori management involving 21,533 patients treated for 5 years revealed eradication rates of 83 percent for triple therapy with amoxicillin and 87 percent with clarithromycin, regardless of the presence or not of bacterial resistance to clarithromycin. [Gut 2021;70:40-54]

“When susceptible to clarithromycin, the effectiveness of triple therapy was 94 percent, dropping to 75 percent in the case of resistance,” the researchers said.

Another study suggested to avoid using first-line triple therapy with clarithromycin or metronidazole when resistances are greater than 15 percent for clarithromycin. [J Clin Med 2020;9:543]

Of note, “quadruple concomitant regimen with metronidazole or tinidazole, recommended by many clinical guidelines, usually provides very good results in those strains sensitive to clarithromycin (95 percent), but the effectiveness decreases in those resistant (86 percent),” Bujanda said

“[T]hus, its use in first-line empirical therapy is questionable, especially in those regions with high resistance to clarithromycin, similar to those of our study,” he added.

“In this same context, regarding the use of metronidazole or tinidazole, in our study, we observed that the sequential regimen with tinidazole obtained eradication rates of 92 percent as compared to 80 percent when metronidazole was used,” Bujanda said.