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. 2000 Jun 3;320(7248):1540.

Treatment of Helicobacter pylori infection

Development of resistance to antibiotics used must be avoided

G Gopal Rao 1,2, J O'Donohue 1,2, C S Mahankali Rao 1,2, H Fidler 1,2
PMCID: PMC1118119  PMID: 10877582

Editor—We agree with de Boer and Tytgat that treatment to eradicate Helicobacter pylori in patients with proved peptic ulcer is cost effective and benefits the patient and society.1 Treatment to eradicate the organism in patients with non-ulcer dyspepsia, however, is contentious. The efficacy, safety, and cost effectiveness are far from proved. Several recent trials, including a multicentre double blind placebo controlled trial, failed to show any significant long term benefit of H pylori eradication treatment in non-ulcer dyspepsia.2,3

In our hospital 12 patients with dyspepsia who had previously received treatment from their general practitioners to eradicate H pylori on the basis of positive serological results were found to have gastric carcinoma. In several cases the delay in referring the patients to a gastroenterologist was considerable (unpublished observations).

Perhaps the most compelling reason to desist from empirical or indiscriminate antibiotic treatment of non-ulcer dyspepsia is the recent observation that commensal oral and bowel flora rapidly develop resistance to antibiotics (clarithromycin, amoxycillin, and metronidazole) used in H pylori eradication treatment. The emergence and persistence of resistant strains was most pronounced in patients treated with clarithromycin.4 If this resistance then spreads to pathogenic bacteria these antibiotics will cease to be useful in a variety of infections. The development of such resistance will far outweigh any perceived benefits of antibiotic treatment of non-ulcer dyspepsia.

Footnotes

Competing interests: None declared.

References

  • 1.De Boer WA, Tytgat GNJ. Treatment of Helicobacter pylori infection. BMJ. 2000;320:31–34. doi: 10.1136/bmj.320.7226.31. . (1 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Blum AL, Talley NJ, O'Morain C, van-Zanten SV, Labenz J, Stolte M, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxycillin Effect One Year after Treatment (OCAY) Study Group. N Engl J Med. 1998;339:1875–1881. doi: 10.1056/NEJM199812243392602. [DOI] [PubMed] [Google Scholar]
  • 3.Talley NJ, Janssens J, Lauritse K, Racz I, Bolling-Sternevald E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up. BMJ. 1999;318:833–837. doi: 10.1136/bmj.318.7187.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Adamsson I, Nord CE, Lundquist P, Sjostedt S, Edlund C. Comparative effects of omeprazole, amoxycillin plus metronidazole versus omeprazole, clarithromycin plus metronidazole on oral, gastric and intestinal microflora of Helicobacter pylori infected patients. J Antimicrob Chemother. 1999;44:629–640. doi: 10.1093/jac/44.5.629. [DOI] [PubMed] [Google Scholar]
BMJ. 2000 Jun 3;320(7248):1540.

Quadruple treatment may be solution

M C Bateson 1

Editor—De Boer and Tytgat review the regimens used for Helicobacter pylori infection and comment correctly that we lack large randomised controlled trials to compare different treatments.1-1 A general finding, however, has been that earlier enthusiasm is not borne out by later experience; probably the old two week triple regimen of bismuth, tetracycline, and metronidazole should join dual treatment and be regarded as obsolete. One week's quadruple treatment with bismuth, tetracycline, and metronidazole plus proton pump inhibitor is more effective and halves the load of the rather toxic bismuth, tetracycline, and metronidazole component which makes it so hard for patients to take.

We should aim to use treatments with a 90% or better success rate per protocol. Even a proton pump inhibitor plus amoxycillin plus metronidazole does not always reach this in modern studies, which report 85-90% cures, and perhaps this regimen should be reserved for second line treatment.

One alternative that has been effective locally is quadruple treatment with lansoprazole 30 mg daily, tetracycline 500 mg twice daily, clarithromycin 250 mg twice daily, and metronidazole 400 mg twice daily for one week.1-2 This has achieved a 95.3% success rate (negative result of a urea breath test one to two months after treatment) in 213 consecutive patients with duodenal ulcers at endoscopy and a positive result of a direct urease test immediately before treatment. Interestingly, all of the first 66 patients had negative results of breath tests, which emphasises the need for larger studies to assess effectiveness accurately. This regimen has been used locally for four years, and a recent audit has shown that the antibiotic sensitivity of H pylori to the drugs used was exactly the same in 1999 as it was in 1992-6. Results were a little better (and early duodenal ulcer healing rates may be expected to be superior) when lansoprazole was used for a month rather than a week. I commend this scheme for general use in treatment.

Footnotes

Competing interests: None declared.

References

BMJ. 2000 Jun 3;320(7248):1540.

Triple regimen based on ranitidine bismuth citrate could be solution

Vincenzo Savarino 1,2,3, Matteo Neri 1,2,3, Sergio Vigneri 1,2,3

Editor—One of the key messages of de Boer and Tytgat's paper on the treatment of Helicobacter pylori infection is that triple regimens combining clarithromycin and metronidazole should not be used as there is no valid empirical back up regimen after failure.2-1 This recommendation is based on the increasing evidence that antibiotic resistance has become the main factor affecting negatively the efficacy of treatment to eradicate H pylori. De Boer and Tytgat's suggestion, however, is in contrast with the guidelines produced by the Maastricht consensus meeting and similar conferences worldwide. The Maastricht meeting recommended the regimens based on the two antibiotics as the best available first line treatments for eradicating H pylori.2-2

De Boer and Tytgat suggest adopting a triple treatment combining a proton pump inhibitor or ranitidine bismuth citrate with amoxycillin and clarithromycin as first line treatment in areas with low primary prevalence of resistance to clarithromycin. But the association of these two antibiotics showed on average a lower eradication rate than the combination of clarithromycin and metronidazole.2-3 The statement that the quadruple regimen containing metronidazole performs well in almost all populations should be more cautious, because a significant negative impact of resistance to metronidazole on the efficacy of this complex scheme has been found.2-4

In recent years a new triple treatment based on the combination of ranitidine bismuth citrate plus clarithromycin and metronidazole has been developed. This provides a high cure rate even in patients with resistant strains2-5 and prevents the induction of secondary resistance when treatment fails, as reported by de Boer and Tytgat themselves in their review. So this triple regimen based on ranitidine bismuth citrate may be considered not only a first choice treatment in areas with a high prevalence of resistance to metronidazole or clarithromycin (thus allowing us to reduce the costs and the frequent adverse effects of two subsequent courses of treatment if eradication is not obtained with the first cycle) but also an effective second line treatment.

Footnotes

Competing interests: Each author has received funding for speaking or research projects and reimbursement for attending a symposium from several companies producing some of the drugs mentioned in this letter.

References

  • 2-1.De Boer WA, Tytgat GNJ. Treatment of Helicobacter pylori infection. BMJ. 2000;320:31–34. doi: 10.1136/bmj.320.7226.31. . (1 January.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-2.European Helicobacter Pylori Study Group. Current European concepts in the management of Helicobacter pylori infection: The Maastricht consensus report. Gut. 1997;41:8–13. doi: 10.1136/gut.41.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-3.Pipkin GA, Williamson R, Wood JR. Review article: one-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori. Aliment Pharmacol Ther. 1998;12:823–837. doi: 10.1046/j.1365-2036.1998.00405.x. [DOI] [PubMed] [Google Scholar]
  • 2-4.Van der Hulst RWM, van der Ende A, Homan A, Roorda P, Dankert J, Tytgat GNJ. Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication. Gut. 1998;42:166–169. doi: 10.1136/gut.42.2.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-5.Savarino V, Zentilin P, Pivari M, Bisso G, Mele MR, Bilardi C, et al. The impact of antibiotic resistance on the efficacy of three 7-day regimens against H pylori infection. Gastroenterology. 1999;116:G1326. doi: 10.1046/j.1365-2036.2000.00780.x. [DOI] [PubMed] [Google Scholar]

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