Meta‐analysis of three‐in‐one single capsule bismuth‐containing quadruple therapy for the eradication of Helicobacter pylori

Abstract

Background Bismuth‐containing quadruple therapy has been suggested as first‐line and rescue alternative for Helicobacter pylori eradication. Our objective was to perform a meta‐analysis evaluating the efficacy and safety of single capsule Pylera® (bismuth, metronidazole, and tetracycline) plus a proton‐pump inhibitor (PPI) in any line of treatment. Methods Studies were selected up to October 2018. Outcomes were eradication and adverse events (AEs) rates pooled using the generic inverse variance method. Results In total, 30 studies (6482 patients) were included in the systematic review. The intention‐to‐treat (ITT) efficacy was 90% (95% CI: 87%‐92%, 21 studies, I2 = 88%) in first‐line therapy, 89% (95% CI: 86%‐93%, 12 studies, I2 = 78%) in second‐line and 82% (95% CI: 78%‐87%, nine studies, I2 = 60%) in third‐line; with no differences by the type or dosage of PPI used. For metronidazole‐resistant infection, the ITT efficacy as first‐line therapy was 93% (95% CI: 90%‐96%, six studies, I2 = 0%). In second‐line therapies where patients had been previously treated with clarithromycin, the ITT efficacy was 90% (95% CI: 87%‐93%, 11 studies, I2 = 78%). The overall incidence of AEs was 43% (95% CI: 35%‐50%, 24 studies, I2 = 92%) and they were mostly mild. In nearly 3% of the cases, treatment was interrupted due to AEs. Conclusions A 10‐day treatment with Pylera® achieved an effective eradication rate of approximately 90% both in first‐ and second‐line therapy. This applies regardless of the type and dose of the PPI, in patients with clarithromycin‐ or metronidazole‐resistant strains, and in those previously treated with clarithromycin.

Twice‐a‐day PPI, tetracycline, metronidazole quadruple therapy with Pylera® or Lactobacillus reuteri for treatment naïve or for retreatment of Helicobacter pylori. Two randomized pilot studies

“…The overall cure rate would therefore vary greatly depending on the proportion with susceptible infections and the effect of duration on effectiveness with resistant strains . Our study and most recent studies of Pylera® from European countries suggest that the prevalence of resistance to metronidazole may be lower than reported, which may be in part responsible for the overall relative high cure rates observed and possibly the lack of the ability to see an effect of PPIs that differ in acid inhibition . Clearly, more studies are needed that provide susceptibility data including confirmation of Etest resistant results with agar dilution.…”

“…7 Our study and most recent studies of Pylera® from European countries suggest that the prevalence of resistance to metronidazole may be lower than reported, 14,29 which may be in part responsible for the overall relative high cure rates observed and possibly the lack of the ability to see an effect of PPIs that differ in acid inhibition. 30 Clearly, more studies are needed that provide susceptibility data including confirmation of Etest resistant results with agar dilution. Overall, the available data suggest that in the presence of metronidazole resistant infection in Western countries, 14-day therapy is likely to be superior to shorter durations and one should not be lulled into a sense of false security by (sh)meta-analyses.…”

Efficacy and safety of twice a day, bismuth‐containing quadruple therapy using high‐dose tetracycline and metronidazole for second‐line Helicobacter pylori eradication

“…Most adverse drug effects were mild and rarely led to the withdrawal of therapy as described . A recent meta‐analysis study also showed that the eradication success rate exceeds 90%, although 43% of the patients experience adverse drug effect …”

“…18 A recent meta-analysis study also showed that the eradication success rate exceeds 90%, although 43% of the patients experience adverse drug effect. 19 Neurological symptoms associated with the use of bismuth are associated with increased blood levels, especially in elderly patients. 20 Nonetheless, only mild dizziness or headache was reported in seven patients irrespective of age in this study.…”

Review: Treatment of Helicobacter pylori Infection 2019

“…One found that a 10day treatment with Pylera ® achieved an effective eradication rate of 90% both in first-and second-line therapy, regardless of the type and dose of the PPI, in patients with clarithromycin-or metronidazole-resistant strains, and in those previously treated with clarithromycin. 54 Another meta-analysis which had more non-English language publications reported a pooled eradication rate of 86%. 55 Although bismuth-based regimens have usually been 10 days in length, one study on a 7-day bismuth-based treatment as second-line showed very high eradication rates of 94% compared to 74% for 14 days of moxifloxacin-based therapy.…”