High‐dose PPI‐amoxicillin dual therapy with or without bismuth for first‐line Helicobacter pylori therapy: A randomized trial

Abstract

Background A reliably highly effective high‐dose proton‐pump inhibitor plus amoxicillin (dual Helicobacter pylori therapy) has remained elusive. We compared whether the addition of bismuth to high‐dose dual therapy would improve the efficacy of high‐dose dual therapy as first‐line treatment. Methods This was an open‐label, randomized single‐center study of 160 treatment‐naive patients with H. pylori infection who were randomly assigned to 14‐day therapy with esomeprazole 40 mg twice a day plus amoxicillin 1 g three times a day with or without bismuth potassium citrate 600 mg (elemental bismuth 220 mg) twice a day. Antibiotic resistance was determined by agar dilution method and eradication by 13C‐urea breath test. Results The per‐protocol eradication rates were 96.1%; 95% CI = 88.9%‐99.2% (73/76) without bismuth vs 93.3%; 95% CI = 85.1%‐97.8% (70/75) with bismuth (P = 0.494). The intention‐to‐treat eradication rates were 92.5%; 95% CI = 84.4%‐97.2% (74/80) without bismuth and 88.8%; 95% CI = 79.7%‐94.7% (71/80) with bismuth (P = 0.416). Resistance to amoxicillin, clarithromycin, metronidazole, and levofloxacin was 0%, 31.7%, 81.4%, and 40.7%, respectively. Smoking reduced treatment effectiveness limited to those not receiving bismuth. The per‐protocol eradication rates were 70% (7/10) vs 100% (66/66) in smokers vs non‐smokers without bismuth (P = 0.002), and 100% (10/10) in smokers vs 92.3% (60/65) in non‐smokers with bismuth (P = 1.0). The adverse event rates were 7.5% (6/80) without bismuth vs 11.3% (9/80) with bismuth (P = 0.416). Conclusions Fourteen‐day high‐dose dual therapy was both effective and safe for first‐line treatment in a region of high prevalence antibiotic resistance. Adding bismuth only improved treatment effectiveness among smokers.

Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection

“…Recently published two randomized controlled trials in China commonly revealed the favorable efficacy of high-dose amoxicillin containing regimens, irrespective of the addition of bismuth. 31,32 High-dose dual therapy including esomeprazole 40 mg bid, and amoxicillin 1 g tid with or without elemental bismuth 220 mg bid for 2 weeks showed comparable efficacy (over 90% eradication success in the PP analysis), irrespective of the antibiotic resistance. 31 Study of PAMB vs. PAM regimen including high dose amoxicillin (esomeprazole 20 mg bid, amoxicillin 1 g tid, and metronidazole 400 mg tid with or without 220 mg elemental bismuth bid) for 2 weeks also showed comparable efficacy (over 90% eradication success in the PP analysis), irrespective of the antibiotic resistance.…”

“…31,32 High-dose dual therapy including esomeprazole 40 mg bid, and amoxicillin 1 g tid with or without elemental bismuth 220 mg bid for 2 weeks showed comparable efficacy (over 90% eradication success in the PP analysis), irrespective of the antibiotic resistance. 31 Study of PAMB vs. PAM regimen including high dose amoxicillin (esomeprazole 20 mg bid, amoxicillin 1 g tid, and metronidazole 400 mg tid with or without 220 mg elemental bismuth bid) for 2 weeks also showed comparable efficacy (over 90% eradication success in the PP analysis), irrespective of the antibiotic resistance. 32 Although metronidazole resistance can be overcome with the additive effect of bismuth, both bismuth and high-dose amoxicillin can both independently theoretically improve treatment outcomes.…”

Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-lineHelicobacter pyloritreatment: a multicentre randomised trial in Japan

“…The efficacy of a low-dose and/or less frequent dual therapy consisting of AMO (2.0 g/day or less) and PPI (twice/day or less) resulted in unacceptable eradication rates 32–34. Recently, high-dose and high-frequency dual therapy, defined as the administration of both AMO (≥2.0 g/day) and PPI (at least twice daily) for 14 days, has been reported to have greater H. pylori eradication efficacy as first-line therapy 35–38. However, side effects and poor patient compliance due to high dose, high administration frequency and long duration of treatment are the most common setbacks.…”

High Primary Antibiotic Resistance of Helicobacter pylori Strains Isolated from Pediatric and Adult Patients in Poland during 2016–2018

“…It should be borne in mind, however, that this applies to strains with low resistance levels (8-32 µg/mL), and higher resistance (>32 µg/mL) may reduce the effectiveness of this therapy from >90% to 60% [32]. Very promising results in the Asian population have been obtained for high-dose double therapy (AMX and PPIs), i.e., eradication rate >90% and low level of side effects (<15%) [33,34]. Avoiding the use of antibiotics with high frequency of resistance among H. pylori strains and the use of AMX, to which no resistance is currently observed in Poland, give hope for a wider use of this therapy.…”