Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

Enteral metronidazole for the prevention of graft versus host disease in pediatric marrow transplant recipients: results of a pilot study

Bone Marrow Transplantation volume 33, pages 1235–1239 (2004)Cite this article

A Corrigendum to this article was published on 01 August 2005

Summary:

The use of enteral antibiotics to prevent acute graft versus host disease (GvHD) has not been studied prospectively in children. We hypothesized the risk of GvHD in pediatric bone marrow transplant (BMT) recipients would be decreased with enteral metronidazole. Eligible subjects included pediatric patients referred to one center for first allogeneic BMT. Enteral metronidazole 20 mg/kg/day divided thrice daily (maximum 750 mg/day) was administered from day −14 to day +35. The risk of GvHD grade II or more severe among subjects treated with metronidazole was compared to historical controls. There were no significant differences between treated (n=19) and historical controls (n=83) with respect to age, gender, prophylaxis, or conditioning regimens, proportion receiving unrelated donor marrow, proportion receiving umbilical cord blood, or transplantation indication. The probability of remaining free of GvHD at day +100 was lower in the treated group (P=0.047). The adjusted relative risk of developing GvHD among subjects treated with metronidazole was 0.36 (95% CI: 0.13–0.997; P=0.05). Five patients were unable to complete the study; two were likely related to study medication. We conclude that enteral metronidazole appears effective in the prevention of GvHD. These results suggest that a randomized trial is justifiable in children, especially recipients of alternative donor BMT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Weisdorf D, Haake R, Blazar B et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990; 75: 1024–1030.

    CAS  PubMed  Google Scholar 

  2. Filipovich AH, Vallera DA, Youle RJ et al. Graft-versus-host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. A pilot study using immunotoxins for T cell depletion of donor bone marrow. Transplantation 1987; 44: 62–69.

    Article  CAS  PubMed  Google Scholar 

  3. Roy J, McGlave PB, Filipovich AH et al. Acute graft-versus-host disease following unrelated donor marrow transplantation: failure of conventional therapy. Bone Marrow Transplant 1992; 10: 77–82.

    CAS  PubMed  Google Scholar 

  4. Weisdorf D, Filipovich A, McGlave P et al. Combination graft-versus-host disease prophylaxis using immunotoxin (anti-CD5-RTA [Xomazyme-CD5]) plus methotrexate and cyclosporine or prednisone after unrelated donor marrow transplantation. Bone Marrow Transplant 1993; 12: 531–536.

    CAS  PubMed  Google Scholar 

  5. Bekkum DWv, Roodenburg J, Heidt PJ, Waaij Dvd . Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. J Natl Cancer Inst 1974; 52: 401–404.

    Article  Google Scholar 

  6. Beelen DW, Haralambie E, Brandt H et al. Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation. Blood 1992; 80: 2668–2676.

    CAS  PubMed  Google Scholar 

  7. Beelen DW, Elmaagacli A, Muller KD et al. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial. Blood 1999; 93: 3267–3275.

    CAS  PubMed  Google Scholar 

  8. Grove D, Mahmoud A, Warren K . Suppression of cell-mediated immunity by metronidazole. Int Archs Allergy Appl Immun 1977; 54: 422–427.

    Article  CAS  Google Scholar 

  9. Tanga MR, Antani JA, Kabade SS . Clinical evaluation of metronidazole as an anti-inflammatory agent. Int Surg 1975; 60: 75–76.

    CAS  PubMed  Google Scholar 

  10. Storb R, Prentice RL, Buckner CD et al. Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment. N Engl J Med 1983; 308: 302–307.

    Article  CAS  PubMed  Google Scholar 

  11. Sutherland L, Singleton J, Sessions J et al. Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut 1991; 32: 1071–1075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ursing B, Alm T, Barany F et al. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result. Gastroenterology 1982; 83: 550–562.

    CAS  PubMed  Google Scholar 

  13. Freston J . Looking for hepatotoxicity, working up patients, and assessing causality. In: Drug-Induced Liver Injury: A National and Global Problem 12–13 February 2001, Westfields Conference Center, Chantilly, VA; 2001; Westfields Conference Center, Chantilly, VA: Food and Drug Administration, 2001.

    Google Scholar 

  14. Hill GR, Ferrara JL . The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood 2000; 95: 2754–2759.

    CAS  PubMed  Google Scholar 

  15. Hill GR, Krenger W, Ferrara JL . The role of cytokines in acute graft-versus-host disease. Cytokines Cell Mol Ther 1997; 3: 257–266.

    CAS  PubMed  Google Scholar 

  16. Ganrot-Norlin K, Stalhandske T, Karlstrom R . Lack of antiinflammatory activity of metronidazole. Acta Pharmacol Toxicol (Copenh) 1981; 49: 130–133.

    Article  CAS  Google Scholar 

  17. Duffy LF, Daum F, Fisher SE et al. Peripheral neuropathy in Crohn's disease patients treated with metronidazole. Gastroenterology 1985; 88: 681–684.

    Article  CAS  PubMed  Google Scholar 

  18. Bradley WG, Karlsson IJ, Rassol CG . Metronidazole neuropathy. Br Med J 1977; 2: 610–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the BMT physicians at CCHMC who cared for the patients in this study: Drs Thomas G Gross, Brett Loechelt, Michael Boyer, Jane Sande and Richard Harris. We would also like to thank Drs Mitchell B Cohen, Beverly L Connelly, and Brett Loechelt for serving as members of the Data Safety Monitoring Board.

Author information

Author notes

  1. S L Guthery: Supported in part by DK 07727, an Institutional National Research Service Award from the National Institutes of Health

Authors and Affiliations

  1. Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, UT, USA

    S L Guthery

  2. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati, OH, USA

    J E Heubi

  3. Division of Hematology and Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    A Filipovich

Authors
  1. S L Guthery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J E Heubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Filipovich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S L Guthery.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guthery, S., Heubi, J. & Filipovich, A. Enteral metronidazole for the prevention of graft versus host disease in pediatric marrow transplant recipients: results of a pilot study. Bone Marrow Transplant 33, 1235–1239 (2004). https://doi.org/10.1038/sj.bmt.1704474

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704474

Keywords

Search

Advanced search

Quick links