Drug Safety

, Volume 17, Issue 1, pp 37–46

Drug-Induced Clostridium difficile-Associated Disease

  • Martin L. Job
  • Norman F. JacobsJr
Review Articles Pharmacoepidemiology

Summary

Clostridium difficile is a spore-forming anaerobe that resides in the colon and is capable of producing gastrointestinal disease in humans.

Factors such as previous exposure to antibacterials and some antineoplastic agents have been reported to promote the overgrowth of C. difficile, with subsequent liberation of potent exotoxins that induce inflammation in the colonic mucosa. Colonisation rates vary, and are higher during infancy and hospitalisation, compared with healthy adults.

Although many antibacterials have been reported to induce disease, those agents that achieve high concentrations in the intestinal lumen and are active against bowel flora are more likely to promote overgrowth of C. difficile. Agents with a high potential to induce C. difficile-associated disease (CDAD) include aminopenicillins, cephalosporins and clindamycin. These antibacterials are capable of reducing normal colonisation resistance within the colon.

The exact incidence of CDAD is unknown. Some reports suggest an incidence of 1 to 3 infections per 100 000 courses of outpatient oral therapy.

The spectrum of illness of CDAD can range from mild diarrhoeal disease to severe colitis, toxic megacolon and sepsis. Fatalities have occurred in some cases. Discontinuation of the offending antibacterial in patients with mild disease is often sufficient to alleviate symptoms. For those with moderate to severe illness, metronidazole and vancomycin are reported to be equally efficacious. Increasing resistance of enterococci to vancomycin limits its use to patients with severe life-threatening infections. Patients with recurrent disease usually respond well to the same course of therapy as was used to treat the initial infection.

CDAD is potentially preventable when appropriate antibacterial selection and infection control measures are implemented.

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References

  1. 1.
    Gerding DDN, Johnson S, Peterson LR et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995; 16: 459–77PubMedCrossRefGoogle Scholar
  2. 2.
    Fekety R. Antibiotic-associated colitis. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. New York: Churchill-Livingstone, 1996: 978–87Google Scholar
  3. 3.
    Aronsson B, Möllby R, Nord CE. Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiologic data from Sweden 1980–1982. J Infect Dis 1985; 151: 476–81PubMedCrossRefGoogle Scholar
  4. 4.
    Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile infection. Gastroenterology 1981; 81: 5–9PubMedGoogle Scholar
  5. 5.
    Nakamura S, Mikawa M, Takabatake M, et al. Isolation of Clostridium difficile from the feces and antibody in sera of young and elderly adults. Microbiol Immunol 1981; 25: 343–51Google Scholar
  6. 6.
    McFarland LV, Mulligan ME, Kwok RYY, et al. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320: 204–10PubMedCrossRefGoogle Scholar
  7. 7.
    Rudensky B, Rosner S, Sonnenblick M, et al. The prevalence and nosocomial acquisition of Clostridium difficile in elderly hospitalized patients. Postgrad Med J 1993; 69: 45–7PubMedCrossRefGoogle Scholar
  8. 8.
    Bartlett JG. Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism. Clin Infect Dis 1994; 18 Suppl. 4: 265S–72SCrossRefGoogle Scholar
  9. 9.
    Reigler M, Sedivy R, Pothoutakis C, et al. Clostridium difficiletoxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 1995; 95: 2004–11CrossRefGoogle Scholar
  10. 10.
    Viscidi R, Laughon BE, Yoken R, et al. Serum antibody response to toxin A and B of Clostridium difficile. J Infect Dis 1983; 148: 93–100PubMedCrossRefGoogle Scholar
  11. 11.
    McFarland LV, Surawicz CM, Stamm WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J Infect Dis 1990; 162: 678–84PubMedCrossRefGoogle Scholar
  12. 12.
    Katz DA, Lynch ME, Littenberg B. Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea. Am J Med 1996; 100: 487–95PubMedCrossRefGoogle Scholar
  13. 13.
    Hooker DK, DiPiro JT. Effect of antimicrobial therapy on bowel flora. Clin Pharm 1988; 7: 878–88PubMedGoogle Scholar
  14. 14.
    Dzink JA, Bartlett JG. In vitro susceptibility of Clostridium difficile isolates from patients with antibiotic-associated diarrhea or colitis. Antimicrob Agents Chemother 1980; 17: 695–8PubMedCrossRefGoogle Scholar
  15. 15.
    Tedesco FJ. Clindamycin and colitis: a review. J Infect Dis 1977; 135 Suppl: 595–8CrossRefGoogle Scholar
  16. 16.
    Privitera G, Scalpellini P, Ortisi G, et al. Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother 1991; 35: 208–10PubMedCrossRefGoogle Scholar
  17. 17.
    Carlberg A, Ahestig K, Nord CE, et al. Intestinal side effects of cefoperazone. J Antimicrob Chemother 1982; 10: 483–7PubMedCrossRefGoogle Scholar
  18. 18.
    Fekety R, Kim K-H, Brow D, et al. Epidemiology of antibiotic-associated colitis: isolation of Clostridium difficile from the hospital environment. Am J Med 1981; 70: 906–8PubMedCrossRefGoogle Scholar
  19. 19.
    Silva J, Fekety R, Werk C, et al. Inciting and etiologic agents of colitis. Rev Infect Dis 1984; 6 Suppl.: 5214–21CrossRefGoogle Scholar
  20. 20.
    Colarian J. Clostridium difficile following antiviral therapy in the acquired immunodeficiency state [letter]. Am J Med 1988; 84: 1081PubMedCrossRefGoogle Scholar
  21. 21.
    Anand A, Glatt AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993; 17: 109–13PubMedCrossRefGoogle Scholar
  22. 22.
    Reinhart WH, Kappeier M, Halter F. Severe pseudomembranous and ulcerative colitis during gold therapy. Endoscopy 1983; 15: 70–2PubMedCrossRefGoogle Scholar
  23. 23.
    Gentric A, Pennec YL. Diclofenac-induced pseudomembranous colitis [letter]. Lancet 1992; 340: 125–7CrossRefGoogle Scholar
  24. 24.
    Jarvis B, Shevchuk YM. Recurrent Clostridium difficile diarrhoea associated with mitoxantrone and etoposide: a case report and review. Pharmacotherapy 1997; 17(3): 606–11PubMedGoogle Scholar
  25. 25.
    Cuzzolin L, Zamberi D, Dowini M, et al. Influence of radiotherapy on intestinal microflora in cancer patients. J Chemother 1992; 4: 176–9PubMedGoogle Scholar
  26. 26.
    Silva J. Update on pseudomembranous colitis. West J Med 1989; 151(6): 644–8PubMedGoogle Scholar
  27. 27.
    Stergachis A, Perera DR, Schnell MM, et al. Antibiotic-associated colitis. West J Med 1984; 140: 217–9PubMedGoogle Scholar
  28. 28.
    Hirschhorn LR, Trnka Y, Onderdonk A, et al. Epidemiology of community-acquired Clostridium difficile-associated diarrhea. J Infect Dis 1994; 160: 127–33CrossRefGoogle Scholar
  29. 29.
    Gerding DN, Olson MM, Peterson LR, et al. Clostridium difficile-associated diarrhea and colitis in adults: a prospective case-controlled epidemiologic study. Arch Intern Med 1986; 146: 95–100PubMedCrossRefGoogle Scholar
  30. 30.
    Jobe BA, Grosley A, Deveney KE, et al. Clostridium difficilecolitis: an increasing hospital-acquired illness. Am J Surg 1995; 169: 480–3PubMedCrossRefGoogle Scholar
  31. 31.
    Kaatz GW, Gitlin SD, Shaberg DR, et al. Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol 1988; 127: 1289–94PubMedGoogle Scholar
  32. 32.
    Johnson S, Clabots CR, Finn FV, et al. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990; 336: 97–100PubMedCrossRefGoogle Scholar
  33. 33.
    Kelly CP, Pouthoulakis C, LaMont JT. Clostridium difficilecolitis. N Engl J Med 1994; 330: 257–62PubMedCrossRefGoogle Scholar
  34. 34.
    Knoop FC, Owens M, Crocker JC. Clostridium difficile: clinical disease and diagnosis. Clin Microbiol Rev. 1993; 6: 251–65PubMedGoogle Scholar
  35. 35.
    Caputo GM, Weitekamp MR, Bacon AE. Clostridium difficileinfection: a common clinical problem for the general internist. J Gen Int Med 1994; 9: 528–32CrossRefGoogle Scholar
  36. 36.
    Jacobs NE. Antibiotic-induced diarrhea and pseudomembranous colitis. Postgrad Med 1994; 95: 111–20PubMedGoogle Scholar
  37. 37.
    Chatilo W, Manthows CA. Clostridium difficile causing sepsis and acute abdomen in critically ill patients. Crit Care Med 1995; 23: 1146–9CrossRefGoogle Scholar
  38. 38.
    Fekety R, Shah AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993; 269: 71–5PubMedCrossRefGoogle Scholar
  39. 39.
    Bartlett JG. The 10 most common questions about Clostridium difficile-associated diarrhea/colitis. Infect Dis Clin Pract 1992; 1: 254–9CrossRefGoogle Scholar
  40. 40.
    Samone MH, Venkataraman L, De Girolami PC, et al. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996; 100: 32–40CrossRefGoogle Scholar
  41. 41.
    Collier MC, Stock F, De Girolami PC, et al. Comparison of pcp-based approaches to molecular analysis of Clostridium difficile. J Clin Microbiol 1996; 34: 1153–7PubMedGoogle Scholar
  42. 42.
    Bergenstein JM, Kramer A, Withman DH, et al. Pseudomembranous colitis: how useful is endoscopy? Surg Endosc 1990; 4: 217–9CrossRefGoogle Scholar
  43. 43.
    Tedesco FJ, Corless JK, Brownstein RE. Rectal sparing in antibiotic-associated pseudomembranous colitis: a prospective study. Gastroenterology 1982; 83: 1259–60PubMedGoogle Scholar
  44. 44.
    Wilcox MH, Spencer RC. Clostridium difficile infection: responses, relapses, and reinfections. J Hosp Pract 1992; 22: 85–92Google Scholar
  45. 45.
    Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhea and colitis. Lancet 1983; II: 1043–6CrossRefGoogle Scholar
  46. 46.
    Anand A, Bahey B, Mir T, et al. Epidemiology, clinical manifestations, and outcome of Clostridium difficile-associateddiarrhea. Am J Gastroenterol 1994; 89: 519–23PubMedGoogle Scholar
  47. 47.
    Werisch C, Parschalk B, Hasenhündl M, et al. Comparison of vancomycin, teicoplanin, metronidazole and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996; 22: 813–8CrossRefGoogle Scholar
  48. 48.
    Fekety R, Silva J, Kaufman C, et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989; 86: 15–9PubMedCrossRefGoogle Scholar
  49. 49.
    Tedesco F, Markham R, Gurwith M, et al. Oral vancomycin for antibiotic-associated pseudomembranous colitis. Lancet 1978; 2: 226–8PubMedCrossRefGoogle Scholar
  50. 50.
    Jones RN, Sader HS, Erwin ME, et al. Emerging multiply-resistant enterococci among clinical isolates. 1. Prevalence data from 97 Medical Center Surveillance Study in the United States. Diagn Microbiol Infect Dis 1995; 21: 85–93PubMedCrossRefGoogle Scholar
  51. 51.
    Fraise AP. The treatment and control of vancomycin-resistant enterocci. J Antimicrob Chemother 1996; 38: 753–6PubMedCrossRefGoogle Scholar
  52. 52.
    Reinke LM, Messick LR. Update on Clostridium difficile-induced colitis, part 2. Am J Hosp Pharm 1994; 51: 1892–1901PubMedGoogle Scholar
  53. 53.
    Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol 1995; 16: 105–13CrossRefGoogle Scholar
  54. 54.
    Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic-associated colitis due to Clostridium difficile. Gut 1986; 27: 1169–72PubMedCrossRefGoogle Scholar
  55. 55.
    Kleinfeld DI, Sharpe RJ, Donta ST. Parenteral therapy for antibiotic-associated pseudomembranous colitis [letter]. J Infect Dis 1988; 157: 389PubMedCrossRefGoogle Scholar
  56. 56.
    Dudley MH, McLaughlin JC, Carrington G, et al. Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea: a randomized double-blind trial. Arch Intern Med 1986; 146: 1101–4PubMedCrossRefGoogle Scholar
  57. 57.
    Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis 1997; 24: 324-33Google Scholar
  58. 58.
    Ariano RE, Zhanel GG, Harding GKM. The role of anion-ex-change resins in the treatment of antibiotic-associated pseudomembranous colitis. Can Med Assoc J 1990; 142(10): 1049–50Google Scholar
  59. 59.
    Tedesco FJ, Gordon D, Fortson WC. Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis. Am J Gastroenterol 1985; 80: 867–8PubMedGoogle Scholar
  60. 60.
    Tedesco FJ. Treatment of recurrent antibiotic-associated pseudomembranous colitis. Am J Gastroenterol 1982; 77: 220–1PubMedGoogle Scholar
  61. 61.
    McFarland L, Surawicz L, Greenberg R, et al. A randomized placebo-controlled trial of Saccharomyces boulardi in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 271: 1913–8PubMedCrossRefGoogle Scholar
  62. 62.
    Klein S, Elmer G, McFarland L, et al. Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardi, in healthy human volunteers. Pharm Res 1993; 10: 1615–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Martin L. Job
    • 1
  • Norman F. JacobsJr
    • 2
  1. 1.School of Pharmacy, Department of Pharmacy PracticeMercer UniversityAtlantaUSA
  2. 2.Department of MedicineDeKalb Medical CenterDecaturUSA

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