Correspondence
Treatment of Antibiotic-Resistant Helicobacter pylori Infection
N Engl J Med 1998; 339:53July 2, 1998
- Article
To the Editor:
In 1996, several European gastroenterologists recommended that first-line treatment of Helicobacter pylori infection should consist of a proton-pump inhibitor combined with two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole), and amoxicillin.1 In the case of treatment failure, either a second course of this triple regimen or quadruple therapy (omeprazole plus bismuth-based triple therapy) is advisable. However, because patient compliance with and tolerance of quadruple therapy is low, alternative treatments are needed for patients who have had no response to two or more courses of a standard triple regimen.
Preliminary in vitro studies have shown that H. pylori is highly susceptible to rifabutin, a spiropiperidyl derivative of rifamycin S. The minimal concentration of rifabutin needed to inhibit the growth of 49 strains by 90 percent was 0.0078 μg per milliliter (as compared with concentrations of 0.25 μg of clarithromycin per milliliter, 0.031 μg of amoxicillin per milliliter, and 4.0 μg of metronidazole per milliliter).2,3 Moreover, rifabutin has an additive bactericidal effect when combined with amoxicillin or metronidazole and selects for a low number of resistant H. pylori mutants.2 These laboratory findings led to an open pilot study to assess the in vivo efficacy and tolerance of rifabutin in the treatment of H. pylori infection.
We enrolled 28 outpatients (mean age, 48±12 years) who had had no response to two or more courses of a standard triple regimen that included a proton-pump inhibitor. All patients underwent endoscopy, with multiple gastric biopsies. H. pylori was found in all patients. After providing informed consent, the patients followed a one-week regimen consisting of 40 mg of pantoprazole twice daily, 1 g of amoxicillin twice daily, and 300 mg of rifabutin once daily. Side effects (recorded in clinical interviews) and compliance (assessed by pill counts) were analyzed at the end of therapy. The [13C]urea breath test was performed four weeks after the completion of treatment.4 The rate of eradication of H. pylori was estimated on the basis of both intention-to-treat analysis and per-protocol analysis. All patients took medications according to the prescribed schedule. One patient had mild diarrhea and nausea but continued the treatment. The rate of eradication of H. pylori was 78.6 percent (95 percent confidence interval, 63.4 to 93.8 percent) for both analyses.
This study shows that rifabutin, in combination with pantoprazole and amoxicillin, is effective against H. pylori in patients who have had no response to two or more courses of standard triple therapy. Adverse effects are mild, and compliance is excellent.
4 ReferencesFrancesco Perri, M.D.
Virginia Festa, M.D.
Angelo Andriulli, M.D.
Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy1
The European Helicobacter pylori Study Group
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Rossi R, Jabes D, Della Bruna C. In vitro activity of rifabutin, a potential antibiotic in the therapy of Helicobacter pylori. Presented at the 6th International Congress for Infectious Diseases, Prague (Czech Republic), 1994. abstract.
3
Kunin CM . Antimicrobial activity of rifabutin. Clin Infect Dis 1996;22:Suppl 1:S3-S13
CrossRef | Web of Science | Medline4
Perri F ,Clemente R ,Pastore M , et al. The 13C-urea breath test as a predictor of intragastric bacterial load and severity of Helicobacter pylori gastritis. Scand J Clin Lab Invest 1998;58:19-27
CrossRef | Web of Science | Medline
- Citing Articles (23)
Citing Articles
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J. P. Gisbert, X. Calvet. (2011) Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Alimentary Pharmacology & Therapeuticsno-no
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J. P. GISBERT, J.-L. GISBERT, S. MARCOS, I. JIMENEZ-ALONSO, R. MORENO-OTERO, J. M. PAJARES. (2008) Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients. Alimentary Pharmacology & Therapeutics 27:4, 346-354
CrossRef3
D. VAN DER POORTEN, P. H. KATELARIS. (2007) The effectiveness of rifabutin triple therapy for patients with difficult-to-eradicate Helicobacter pylori in clinical practice. Alimentary Pharmacology & Therapeutics 26:11-12, 1537-1542
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Pedro González Carro, Francisco Pérez Roldán, Aurora De Pedro Esteban, Maria L. Legaz Huidobro, Susana Soto Fernández, Oscar Roncero Garcia Escribano, Jose M. Esteban López-Jamar, Carmen Pedraza Martin, Francisco Ruíz Carrillo. (2007) Efficacy of rifabutin-based triple therapy in Helicobacter
pylori infected patients after two standard treatments. Journal of Gastroenterology and Hepatology 22:1, 60-63
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J. P. GISBERT, J. L. GISBERT, S. MARCOS, R. MORENO-OTERO, J. M. PAJARES. (2006) Third-line rescue therapy with levofloxacin is more effective than rifabutin rescue regimen after two Helicobacter pylori treatment failures. Alimentary Pharmacology and Therapeutics 24:10, 1469-1474
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S. MIEHLKE, K. HANSKY, W. SCHNEIDER-BRACHERT, C. KIRSCH, A. MORGNER, A. MADISCH, E. KUHLISCH, E. BASTLEIN, E. JACOBS, E. BAYERDORFFER, N. LEHN, M. STOLTE. (2006) Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Alimentary Pharmacology and Therapeutics 24:2, 395-403
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T. J. BORODY, G. PANG, A. R. WETTSTEIN, R. CLANCY, K. HERDMAN, R. SURACE, R. LLORENTE, C. NG. (2006) Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection. Alimentary Pharmacology and Therapeutics 23:4, 481-488
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J. P. GISBERT, J. L. GISBERT, S. MARCOS, D. OLIVARES, J. M. PAJARES. (2005) Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin. Alimentary Pharmacology and Therapeutics 22:10, 1041-1046
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Javier P. Gisbert, Jose Maria Pajares. (2005) Helicobacter pylori"Rescue" Therapy After Failure of Two Eradication Treatments. Helicobacter 10:5, 363-372
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Javier P. Gisbert, Xavier Calvet, Luis Bujanda, Santiago Marcos, Jose Luis Gisbert, Jose Maria Pajares. (2003) 'Rescue' Therapy with Rifabutin after Multiple Helicobacter pylori Treatment Failures. Helicobacter 8:2, 90-94
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J. P. Gisbert, J. M. Pajares. (2002) Helicobacter pylori 'rescue' regimen when proton pump inhibitor-based triple therapies fail. Alimentary Pharmacology and Therapeutics 16:6, 1047-1057
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Francesco Perri, Virginia Festa, Rocco Clemente, Maria Rosaria Villani, Michele Quitadamo, Nazario Caruso, Michele Bergoli, Angelo Andriulli. (2001) Randomized study of two "rescue" therapies for helicobacter pylori-infected patients after failure of standard triple therapies. The American Journal of Gastroenterology 96:1, 58-62
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