What regimens eradicate Helicobacter pylori?

Journal of Family Practice, Oct, 2003 by Wail Malaty, Sue Stigleman

* EVIDENCE-BASED ANSWER

Fourteen-day triple therapy with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole is superior to 7-day therapy in eradicating Helicobacter pylori (strength of recommendation [SOR]: A, high-quality meta-analysis).

Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective (SOR: A, high-quality systematic review).

Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective (SOR: B, unblinded randomized controlled trial).

* EVIDENCE SUMMARY

The ideal H pylori eradication regimen should reach an intention-to-treat cure rate of 80% (Table). (1) Effective regimens are:

Fourteen-day triple therapy of PPI clarithromycin metronidazole or amoxicillin. A meta-analysis of 13 studies found the eradication rate for 14-day therapy was 81% (95% confidence interval [CI], 77%-85%), compared with 72% (95% CI, 68%-76%) for 7-day therapy. The eradication rate for 10-day therapy (83%; 95% CI, 75%-89%), however, was not significantly better than that for 7-day therapy (80%; 95% CI, 71%-86%). (2) Side effects were more frequent in the longer therapies, but did not lead to discontinuation of therapy.

Seven-day triple therapy of PPI clarithromycin metronidazole or amoxicillin. A high-quality systematic review of 82 studies using 7-day triple therapy found clarithromycin 500 twice daffy yielded a higher eradication rate than clarithromycin 250 mg twice daily when combined with a PPI and amoxicillin (87% vs 81%; P<.0001). When clarithromycin was combined with a PPI and metronidazole, the higher dose of clarithromycin did not yield significantly higher eradication rates (88% vs 89%, P=.259). (3)

Seven-day triple therapy of ranitidine bismuth citrate clarithromycin metronidazole or amoxicillin For these therapies, a high-quality systematic review of 8 studies reported eradication rates of 81% (95% CI, 77%-84%) with amoxicillin and 88% (95% CI, 85%-90%) with metronidazole. (4,5) Side effects were not reported in a uniform manner for the 7-day therapies, but were noted to be mild and did not lead to significant discontinuation of therapy. Pooled dropout rates were similar among all regimens. (4)

Three-day quadruple therapy of PPI bismuth clarithromycin metronidazole or PPI clarithromycin amoxicillin metronidazole. An otherwise high-quality but unblinded randomized clinical trial of 234 patients demonstrated that 2 days of pretreatment with lansoprazole followed by 3 days of lansoprazole with clarithromycin, amoxicillin, and metronidazole yielded eradication rates comparable with 5-day treatment (81% vs. 89%; P<.05). (6)

Another randomized clinical trial of 118 patients, blinded to investigators but not patients, showed that quadruple 3-day therapy with lansoprazole bismuth clarithromycin metronidazole was as effective as 7 days of lansoprazole clarithromycin metronidazole (87% vs 86%; P=.94), and had significantly shorter duration of side effects (2.6 vs 6.2 days; P<.001). Eradication rates were similar in isolates that were resistant or sensitive to either metronidazole or clarithromycin. (7)

The problems of emerging clarithromycin and metronidazole resistance have not been extensively studied. In 1 review, metronidazole-containing regimens eradicated metronidazole-sensitive strains more effectively than metronidazole-resistant strains (weighted difference, 15%; 95% CI, 8%-20%). (4) When an infection is resistant to metronidazole, amoxicillin should be used instead. (4) In areas of high clarithromycin and metronidazole resistance, a quadruple regimen might be more effective. (7)

* RECOMMENDATIONS FROM OTHERS

The Maastricht Consensus of the European Heliobacter Study Group (1) recommends a 7-day triple regimen of PPI clarithromycin either metronidazole or amoxicillin or (if clarithromycin resistance is prevalent) PPI amoxicillin 500 mg 3 times daily metronidazole 500 mg 3 times daily.

The American College of Gastroenterology recommends 14-day therapy of one of the following options: (8)

* PPI clarithromycin (metronidazole or amoxicillin), or ranitidine bismuth citrate clarithromycin (metronidazole or amoxicillin). Tetracycline 500 mg twice a day can be substituted for amoxicillin or metronidazole

* PPI bismuth subsalicylate 525 mg metronidazole 500 mg 3 times daily tetra-cycline 500 mg 4 times daily

* Bismuth subsalicylate 525 mg 4 times daily metronidazole 250 mg 4 times daily tetracycline 500 mg 4 times daily H2 receptor antagonist in standard acid-suppression dose (eg, famotidine 20 mg twice a day for 4 weeks).

The Institute for Clinical Systems Improvement recommends as first-choice treatment a 7-day PPI/clarithromycin/amoxicillin combination, and as second choice a 7-day regimen of PPI, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subsalicylate 525 mg 4 times daily. (9)