Korean J Gastroenterol.  2009 Jul;54(1):5-12. 10.4166/kjg.2009.54.1.5.

Management of Antibiotics-Associated Diarrhea

• Park HS
• Han DS

• KMID: 1792760
• DOI: http://doi.org/10.4166/kjg.2009.54.1.5

Abstract

Antibiotics-associated diarrhea (AAD) is defined as unexplained diarrhea that occurs with the administration of antibiotics. Approximately 20% AAD cases are due to Clostridium difficile. Over the last decade, the incidence of Clostridium difficile-associated disease (CDAD) has progressively increased, and now a significant clinical problem. Recent change in the epidemiology of CDAD and the emergence of an epidemic hypervilruent strain suggest the need for greater attention for infection control, early diagnosis, and more effective treatment modality. However, since most cases of CDAD are both iatrogenic and nosocomial, careful selection of antibiotics, combined with proper hand hygiene and precaution by medical staffs are required.

Keyword

Antibiotics-associated diarrhea (AAD); C. difficile; Clostridium difficile-associated disease (CDAD)

MeSH Terms

Anti-Bacterial Agents/*adverse effects/therapeutic use
*Clostridium difficile
Diarrhea/*etiology
Enterocolitis, Pseudomembranous/diagnosis/*etiology/therapy
Humans
Immunotherapy
Recurrence

Reference

1. Redelings MD, Sorvillo F, Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004. Emerg Infect Dis. 2007; 13:1417–1419.

2. Vonberg RP, Reichardt C, Behnke M, et al. Costs of nosocomial Clostridium difficile-associated diarrhoea. J Hosp Infect. 2008; 70:15–20.

3. Kyne L, Warny M, Qamar A, et al. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000; 342:390–397.

4. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994; 330:257–262.

5. Shim JK, Johnson S, Samore MH, et al. Primary symptom-less colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet. 1998; 351:633.

6. Dial S, Delaney JA, Schneider V, et al. Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy. CMAJ. 2006; 175:745–748.

7. Carignan A, Allard C, Pepin J, et al. Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain. Clin Infect Dis. 2008; 46:1838–1843.

8. Bacon AE, Fekety R. Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea. Diagn Microbiol Infect Dis. 1994; 18:205–209.

9. Wilcox MH, Mooney L, Bendall R, et al. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemothe. 2008; 62:388–396.

10. Dial S, Delaney A, Barkun AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005; 294:2989–2995.

11. Byun TJ, Han DS, Ahn SB, et al. Clinical characteristics and changing epidemiology of Clostridium difficile-associated disease (CDAD). Korean J Gastroenterol. 2009; 54:13–19.

12. Lee HL, Han DS, Kim JB, et al. A case of pseudomembranous colitis presenting as toxic megacolon and protein losing enteropathy. Korean J Gastroenterol. 2003; 41:410–413.

13. Na KS, Jun DW, Park EJ, et al. A case of pseudomembranous colitis associated with neutrocytic ascites. Korean J Gastrointest Endosc. 2000; 21:568–571.

14. Koh DH, Lee HL, Kim JM, et al. A case of toxic megacolon associated with fulminant pseudomembranous colitis. Korean J Gastrointest Endosc. 2008; 36:112–116.

15. O'Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009; 136:1913–1924.

16. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005; 353:2442–2449.

17. Warny M, Pepin J, Fang A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet. 2005; 366:1079–1084.

18. Hong YR, Jeong SH, Kim KB, et al. Diagnosis of anti-biotic-associated diarrhea and pseudomembranous colitis by direct detection of Clostridium difficile toxin B gene. Infect Chemother. 2003; 35:241–248.

19. Lyras D, O'Connor JR, Howarth PM, et al. Toxin B is essen-tial for virulence of Clostridium difficile. Nature. 2009; 458:1176–1179.

20. Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med. 2002; 346:334–339.

21. Blossom DB, McDonald LC. The challenges posed by re-emerging Clostridium difficile infection. Clin Infect Dis. 2007; 45:222.

22. Planche T, Aghaizu A, Holliman R, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis. 2008; 8:777–784.

23. McFarland LV. Update on the changing epidemiology of Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol. 2008; 5:40–48.

24. Shin BM, Kuak EY, Yoo HM, et al. Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005. J Med Microbiol. 2008; 57:697–701.

25. Shin BM, Kuak EY, Yoo SJ, et al. Emerging toxin A-B+ variant strain of Clostridium difficile responsible for pseudomembranous colitis at a tertiary care hospital in Korea. Diagn Microbiol Infect Dis. 2008; 60:333–337.

26. Reller ME, Lema CA, Perl TM, et al. Yield of stool culture with isolate toxin testing versus a two-step algorithm including stool toxin testing for detection of toxigenic Clostridium difficile. J Clin Microbiol. 2007; 45:3601.

27. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2008. CD004611.

28. Wanahita A, Goldsmith EA, Marino BJ, et al. Clostridium difficile infection in patients with unexplained leukocytosis. Am J Med. 2003; 115:543–546.

29. Baines SD, O'Connor R, Freeman J, et al. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. J Antimicrob Chemother. 2008; 62:1046–1052.

30. Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007; 45:302–307.

31. Gerding DN, Johnson S, Peterson LR, et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459–477.

32. Johnson S, Homann SR, Bettin KM, et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, place-bo-controlled trial. Ann Intern Med. 1992; 117:297–302.

33. Leffler DA, LaMont JT. Treatment of Clostridium difficile-associated disease. Gastroenterology. 2009; 136:1899–1912.

34. Maroo S, Lamont JT. Recurrent Clostridium difficile. Gastroenterology. 2006; 130:1311–1316.

35. O'Connor JR, Galang MA, Sambol SP, et al. Rifampin and rifaximin resistance in clinical isolates of Clostridium difficile. Antimicrob Agents Chemother. 2008; 52:2813–2817.

36. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis. 2006; 43:421–427.

37. Peppe J, Porzio A, Davidson DM. A new formulation of tole-vamer, a novel nonantibiotic polymer, is safe and well-tol-erated in healthy volunteers: a randomized phase I rial. Br J Clin Pharmacol. 2008; 66:102–109.

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

39. Segarra-Newnham M. Probiotics for Clostridium difficile-associated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii. Ann Pharmacother. 2007; 41:1212–1221.

40. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006; 101:812–822.

41. Pothoulakis C, Kelly CP, Joshi MA, et al. Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum. Gastroenterology. 1993; 104:1108–1115.

42. Juang P, Skledar SJ, Zgheib NK, et al. Clinical outcomes of intravenous immune globulin in severe Clostridium difficile-associated diarrhea. Am J Infect Control. 2007; 35:131–137.

43. Borody TJ, Warren EF, Leis SM, et al. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol. 2004; 38:475–483.

44. You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med. 2008; 148:632–633.

45. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. 1989; 320:204–210.

46. Kuijper EJ, van Dissel JT, Wilcox MH. Clostridium difficile: changing epidemiology and new treatment options. Curr Opin Infect Dis. 2007; 20:376–383.

47. Hookman P, Barkin JS. Clostridium difficile-associated infection, diarrhea and colitis. World J Gastroenterol. 2009; 15:1554–1580.