- Design
- Systematic review and meta-analysis (12 comparative studies, randomised and non-randomised)
- Population
- 1,192 adults with documented clarithromycin-resistant H. pylori in comparative studies
- Primary outcome
- H. pylori eradication rate
- Effect
- 74.7% vs 52.7%, RR 1.42 (95% CI 1.14–1.76); vonoprazan RR 1.78 (1.55–2.04)
This systematic review included 20 publications on adults with documented clarithromycin-resistant Helicobacter pylori; 12 comparative studies (randomised and non-randomised) contributed to the main analysis.
Eradication was achieved in 74.7% of 621 patients on potassium-competitive acid blocker (P-CAB) regimens versus 52.7% of 571 on proton pump inhibitor (PPI) regimens (RR 1.42, 95% CI 1.14–1.76). Vonoprazan regimens showed the largest effect (RR 1.78, 1.55–2.04); tegoprazan regimens were also superior (RR 1.26, 1.04–1.54). The gain was greatest when clarithromycin was still part of the triple therapy (RR 1.79).
The logic is pharmacological: stronger, faster acid suppression raises gastric pH enough for amoxicillin to work, partly compensating for a resistant organism. But a 75% eradication rate is still below the 90% target for any first-line regimen, and several included studies were not randomised. The better conclusion is to avoid clarithromycin where resistance is likely — and where a P-CAB is available, to use it in place of a PPI in whatever regimen is chosen.
- Where clarithromycin resistance is known or likely, avoid clarithromycin triple therapy altogether if an alternative exists.
- If a potassium-competitive acid blocker such as vonoprazan is available, prefer it to a PPI in eradication regimens.
- Confirm eradication with a urea breath test or stool antigen at least four weeks after treatment, off PPI for two weeks.
- Ask about previous macrolide use — it is the simplest predictor of clarithromycin resistance.
- Even with a P-CAB, success in resistant infection was about 75%, below the 90% goal for a first-line regimen.
Why it matters
It points to the acid blocker, not just the antibiotic, as a lever for rescuing failing eradication therapy.
Don't overread it
The pooled evidence mixes randomised and non-randomised studies, and 75% eradication is still not good enough for first-line use in resistant infection.
The statistics, in plain English
An RR of 1.42 means about 42% more patients cleared the infection — in absolute terms, 22 more per 100 treated. The P value is very small, but when non-randomised studies are pooled, confounding can inflate an effect.
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