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Clarithromycin Versus Metronidazole in First-Line Helicobacter Pylori Triple Eradication Therapy Based on Resistance
Masaki Murata1,2, Mitsushige Sugimoto3,4, Hitomi Mizuno5
1Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan.
Background:
International treatment guidelines for Helicobacter pylori infection recommend a proton pump inhibitor (PPI)/amoxicillin/clarithromycin (CAM) regimen (PAC) or PPI/amoxicillin/metronidazole (MNZ) regimen (PAM) as first-line therapy based on culture and sensitivity testing. As incidence rates of antimicrobial agent-resistant strains are changing year by year, it is important to reevaluate the efficacy of eradication regimens. We performed a meta-analysis to evaluate the efficacy and safety of PAC and PAM based on different locations categorized by the reported incidence of CAM- and MNZ-resistant strains.
Methods:
Randomized control trials (RCTs) comparing eradication rates between PAC and PAM first-line treatment up to December 2018 were included. We divided RCTs into four groups based on resistance to CAM (< 15% or ≥ 15%) and MNZ (< 15% or ≥ 15%).
Results:
A total of 27 studies (4825 patients) were included. Overall eradication rates between PAC and PAM were similar (74.8% and 72.5%, relative risk (RR): 1.13, 95% confidence interval (CI): 0.91-1.39, P = 0.27) in the intention-to-treat analysis. In areas with low MNZ- and high CAM-resistance rates, PAM had a significantly higher eradication rate than PAC (92.5% vs. 70.8%, RR: 0.29, 95% CI: 0.13-0.68). In areas with high MNZ- and low CAM-resistance rates, the eradication rate with PAC was only 72.9%.
Conclusions:
Overall eradication rates with PAC and PAM were equivalent worldwide. In low MNZ-resistance areas, PAM may be recommended as first-line therapy. However, the efficacy of PAC may be insufficient, irrespective of susceptibility to CAM.
Insights
First-line Helicobacter pylori treatment with proton pump inhibitor/amoxicillin/clarithromycin (PAC) or PPI/amoxicillin/metronidazole (PAM) regimens show similar global efficacy. However, PAM is more effective in areas with low metronidazole resistance and high clarithromycin resistance.
Area of Science:
- Gastroenterology
- Infectious Diseases
- Pharmacology
Background:
- International guidelines recommend proton pump inhibitor (PPI)/amoxicillin/clarithromycin (PAC) or PPI/amoxicillin/metronidazole (PAM) for H. pylori eradication.
- Antimicrobial resistance patterns evolve, necessitating reevaluation of treatment efficacy.
- This meta-analysis assesses PAC vs. PAM efficacy based on regional resistance rates.
Purpose of the Study:
- To compare the efficacy and safety of PAC and PAM regimens for H. pylori eradication.
- To analyze regimen effectiveness in relation to local antimicrobial resistance patterns.
Main Methods:
- Systematic meta-analysis of randomized controlled trials (RCTs) comparing PAC and PAM as first-line therapy.
- Studies were categorized by clarithromycin (CAM) and metronidazole (MNZ) resistance rates (<15% or ≥15%).
- Data analysis included intention-to-treat and subgroup analyses based on resistance profiles.
Main Results:
- Overall eradication rates were similar between PAC (74.8%) and PAM (72.5%).
- In regions with low MNZ and high CAM resistance, PAM demonstrated significantly higher eradication rates (92.5%) than PAC (70.8%).
- PAC efficacy was suboptimal (72.9%) in areas with high MNZ and low CAM resistance.
Conclusions:
- PAC and PAM exhibit equivalent overall H. pylori eradication rates globally.
- PAM is recommended as a first-line option in areas characterized by low metronidazole resistance.
- PAC efficacy may be compromised, regardless of clarithromycin susceptibility, in certain resistance landscapes.
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