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What regimens eradicate Helicobacter pylori?

* 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)

* CLINICAL COMMENTARY

Patients beginning complex regimens require counseling

The most effective regimens (>80% eradication) for H pylori include a 10- to 14-day course of at least 2 antibiotics and an antisecretory agent. However, even optimal treatment regimens can fail in approximately 10% of patients. Poor compliance is among the most common reasons for treatment failure. Medication side effects can affect up to 50% of patients taking triple-agent regimens.

Treatment regimens with multiple medications administered several times daily can be difficult to follow. Convenient packaging containing all daily medications are available to optimize adherence.

Counseling points for patients should include how to take the medicine correctly, expected side effects, the importance of completing the entire therapy regimen, and warnings of specific interactions (eg, alcohol and metronidazole). Lastly, the patient should be made aware of the cost of the entire regimen, which ranges from $50 to $250.

Laura B. Hansen, PharmD, BCPS, University of Colorado Health Sciences Center, Denver, Colorado

REFERENCES

(1.) Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Heliobacter Pylori Study Group. Gut 1997; 41:8-13.

(2.) Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxicillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 2000; 14:603-609.

(3.) Huang J, Hunt RH. The importance of clarithromycin dose in the management of Helicobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. Aliment Pharmacol Ther 1999; 13:719-729.

(4.) Janssen MJ, Van Oijen AH, Verbeek AL, Jansen JB, De Boer WA. A systematic comparison of triple therapies for treatment of Helicobacter pylori infection with proton pump inhibitor/ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole. Aliment Pharmacol Ther 2001; 15:613-624.

(5.) Delaney B, Moayyedi, P, Forman, D. Helicobacter pylori. Clin Evid [online], Issue 8. London: BMJ Publishing Group, Last updated 2003 March. Available at www.ovid.com. Accessed on March 4, 2003.

(6.) Treiber G, Wittig J, Ammon S, Walker S, van Doom LJ, Klotz U. Clinical outcome and influencing factors for a new short-term quadruple therapy for Heliobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med 2002; 162:153-160.

(7.) Wong BC, Wang WH, Wong WM, et al. Three-day lansoprazole quadruple therapy for Heliobacter pylori-positive duodenal ulcers: a randomized controlled study. Aliment Pharmacol Ther 2001; 15:843-849.

(8.) Howden CW, Hunt RH, Guidelines for the management of Heliobacter pylori infection. Ad Hoc Committee on the Practice Parameters of the American College of Gastroenterology.Am J Gastroenterol 1998; 93:2330-2338.

(9.) Institute for Clinical Systems Improvement (ICSI). Dyspepsia. Bloomington, Minn: ICSI; last updated January 2003. Available at: http://www.icsi.org/ knowledge/detail.asp?catID=29&itemID=171. Accessed on September 8, 2003.

Wail Malaty, MD, Mountain Area Health Education Center Rural Track Family Practice Residency, Hendersonville, NC; Sue Stigleman, MLS, Health Science Library, Mountain Area Health Education Center, Asheville, NC
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Title Annotation:Clinical inquiries: from the family practical inquiries network
Author:Malaty, Wail; Stigleman, Sue
Publication:Journal of Family Practice
Geographic Code:1USA
Date:Oct 1, 2003
Words:1226
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