Original Contribution | Published:

Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease

American Journal of Gastroenterology volume 97, pages 17691775 (2002) | Download Citation

Subjects

Abstract

OBJECTIVE:

There is currently uncertainty as to the best treatment for patients with recurrent episodes of Clostridium difficile disease (RCDD). Our objective was to evaluate the success of treatment strategies in a cohort of 163 RCDD patients.

METHODS:

Data were used from patients who had participated in the placebo arm in two national referral clinical trials evaluating a new combination treatment. Patients with active RCCD were enrolled, prescribed either vancomycin or metronidazole, and randomized to either the investigational biological or a placebo. All patients were observed for at least 2 months for a subsequent episode of RCCD.

RESULTS:

Of the 163 cases, 44.8% recurred. A tapering course of vancomycin resulted in significantly fewer recurrences (31%, p = 0.01), as did pulsed dosing of vancomycin (14.3%, p = 0.02). A trend (p = 0.09) for a lower recurrence frequency was observed for high-dose (≥2 g/day) vancomycin and low-dose (≤1 g/day) metronidazole. Vancomycin was significantly more effective in clearing C. difficile culture and/or toxin by the end of therapy than metronidazole (89% vs 59%, respectively; p < 0.001).

CONCLUSIONS:

These data show that tapered or pulsed dosing regimens of vancomycin may result in a significantly better cure of RCDD. The persistence of C. difficile spores suggests that additional strategies to restore the normal colonic microflora may also be beneficial.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Treatment of Clostridium difficile-associated diarrhea and colitis. Curr Top Microbiol Immunol 2000;250:127–139.

  2. 2.

    , , , et al. Clostridium difficile-associated diarrhoea in hospitalised patients. J Clin Pharmacol Ther 2000;25:101–109.

  3. 3.

    AHA Resource Center. Fast facts on U.S. hospitals from Hospital Statistics. American Hospital Association: Chicago. Available from: . Accessed May 1, 2002.

  4. 4.

    , National hospital discharge survey: Annual summary, 1998. Vital Health Stat 13 2000;148:1–194.

  5. 5.

    , , , et al. National Nosocomial Infections Surveillance System. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol 2000;21:510–515.

  6. 6.

    , , Clostridium difficile-associated diarrhea. A review. Arch Intern Med 2001;161:525–533.

  7. 7.

    , , , et al. Recurrent Clostridium difficile disease: Epidemiology and clinical characteristics. Infect Control Hosp Epidemiol 1999;20:43–50.

  8. 8.

    , , , et al. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994;15:371–381.

  9. 9.

    , , Increasing hospitalization and death possibly due to Clostridium difficile diarrheal disease. Emerg Infect Dis 1998;4:619–625.

  10. 10.

    , , , et al. Acute abdomen and Clostridium difficile colitis: Still a lethal combination. Dig Surg 2000;17:160–163.

  11. 11.

    , , Clostridium difficile-associated diseases. The clinical courses of 18 fatal cases. Intensive Care Med 2000;26:416–421.

  12. 12.

    , , , et al. Clostridium difficile—a common and costly colitis. Dis Colon Rectum 1991;34:244–248.

  13. 13.

    Clinical impact and associated costs of Clostridium difficile-associated disease. J Antimicrob Chemother 1998;41(suppl C):5–12.

  14. 14.

    , , , et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994;271:1913–1918.

  15. 15.

    , , , et al. Recurrent Clostridium difficile diarrhea: Characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis 1997;24:324–333.

  16. 16.

    , , , et al. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol 2000;38:2386–2388.

  17. 17.

    Treatment of Clostridium difficile infection. J Antimicrob Chemother 1998;41(suppl C):41–46.

  18. 18.

    Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol 1997;92:739–750.

  19. 19.

    , , , et al. Metronidazole may inhibit intestinal colonization with Clostridium difficile. Dis Colon Rectum 1998;41:464–467.

  20. 20.

    , , , et al. The search for a better treatment for recurrent Clostridium difficile disease: Use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000;31:1012–1017.

  21. 21.

    , , , et al. Recovery of spores of Clostridium difficile altered by heat or alkali. J Med Microbiol 1989;28:217–221.

  22. 22.

    , , , et al. Risk factors for early recurrent Clostridium difficile-associated diarrhea. Clin Infect Dis 1998;26:954–959.

  23. 23.

    , , , et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhoea and colitis. Lancet 1983;ii:1043–1046.

  24. 24.

    , , , et al. Metronidazole: An alternate therapy for antibiotic-associated colitis. Gastroenterology 1982;82:849–851.

  25. 25.

    , Antibiotic-associated colitis: Why do patients relapse? Gastroenterology 1986;90:1098–1099.

  26. 26.

    , , , et al. Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and C. difficile-associated diarrhea. Antimicrob Agents Chemother 1992;36:2192–2196.

  27. 27.

    , , , et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: Comparison of two dosage regimens. Am J Med 1989;86:15–19.

  28. 28.

    , , . Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomycin and rifampin. J Clin Gastroenterol 1987;9:155–159.

  29. 29.

    , , Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis. Am J Gastroenterol 1985;80:867–868.

  30. 30.

    , , , et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996;22:813–818.

  31. 31.

    , , , et al. Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain. Eur J Clin Microbiol 1987;6:51–53.

  32. 32.

    , Bacteriotherapy for chronic relapsing C. difficile diarrhoea in six patients. Lancet 1989;1(8648):1156–1160.

  33. 33.

    , , , et al. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of normal faeces. Scand J Infect Dis 1984;16:211–215.

  34. 34.

    , Whole-bowel irrigation as an adjunct to the treatment of chronic, relapsing Clostridium difficile colitis. J Clin Gastroenterol 1996;22:186–189.

  35. 35.

    , Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol 2000;95:3283–3285.

  36. 36.

    , , Fusidic acid for the treatment of antibiotic-associated colitis induced by Clostridium difficile. Infection 1984;12:276–279.

  37. 37.

    , , , et al. Relapse of antibiotic associated colitis: Endogenous persistence of Clostridium difficile during vancomycin therapy. Gut 1983;24:206–212.

  38. 38.

    , , , et al. Symptomatic relapse after oral vancomycin therapy of antibiotic-associated-pseudomembranous colitis. Gastroenterology 1980;78:431–434.

  39. 39.

    , , , et al. Clostridium difficile colitis: Factors influencing treatment failure and relapse—a prospective evaluation. Am J Gastroenterol 1998;93:1873–1876.

  40. 40.

    Normal flora: Diversity and functions. Microb Ecol Health Dis 2000;12:193–207.

  41. 41.

    , , , et al. Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. Infect Immun 2001;69:2762–2765.

Download references

Acknowledgements

This study was supported by Laboratoires Biocodex, France.

Author information

Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA

    • Lynne V McFarland
    •  & Gary W Elmer
  2. Biocodex, Inc., Seattle, Washington, USA

    • Lynne V McFarland
  3. Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, USA

    • Christina M Surawicz

Authors

  1. Search for Lynne V McFarland in:

  2. Search for Gary W Elmer in:

  3. Search for Christina M Surawicz in:

Corresponding author

Correspondence to Christina M Surawicz.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1111/j.1572-0241.2002.05839.x

Further reading