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Clostridium difficile infection: clinical spectrum and approach to management

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Abstract

Clostridium difficile is recognized globally as an important enteric pathogen associated with considerable morbidity and mortality due to the widespread use of antibiotics. The overall incidence of C. difficile-associated diarrhea (CDAD) is increasing due to the emergence of a hypervirulent strain known as NAP1/BI/027. C. difficile acquisition by a host can result in a varied spectrum of clinical conditions inclusive of both colonic and extracolonic manifestations. Repeated occurrence of CDAD, manifested by the sudden re-appearance of diarrhea and other symptoms usually within a week of stopping treatment, makes it a difficult clinical problem. C. difficile infection has also been reported to be involved in exacerbation of inflammatory bowel diseases. The first step in the management of a suspected CDAD case is the withdrawal of the offending agent and changing the antibiotic regimens. Antimicrobial therapy directed against C. difficile viz. metronidazole for mild cases and vancomycin for severe cases is needed. For patients with ileus, oral vancomycin with simultaneous intravenous (IV) metronidazole and intracolonic vancomycin may be given. Depending on the severity of disease, the further line of management may include surgery, IV immunoglobulin treatment or high dose of vancomycin. Adjunctive measures used for CDAD are probiotics and prebiotics, fecotherapy, adsorbents and immunoglobulin therapy. Among the new therapies fidaxomicin has recently been approved by the American Food and Drugs Administration for treatment of CDAD.

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References

  1. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431–55.

    Article  PubMed  Google Scholar 

  2. Crogan NL, Evans BC. Clostridium difficile: an emerging epidemic in nursing homes. Geriatr Nurs. 2007;28:161–4.

    Article  PubMed  Google Scholar 

  3. Yassin SF, Young-Fadok TM, Zein NN, Pardi DS. Clostridium difficile associated diarrhea and colitis. Mayo Clin Proc. 2001;76:725–30.

    Article  PubMed  CAS  Google Scholar 

  4. Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 1997;92:739–50.

    PubMed  CAS  Google Scholar 

  5. Modena S, Bearelly D, Swartz K, Friedenberg FK. Clostridium difficile among hospitalized patients receiving antibiotics: a case–control study. Infect Control Hosp Epidemiol. 2005;26:685–90.

    Article  PubMed  Google Scholar 

  6. Best EL, Fawley WN, Parnell P, Wilcox MH. The potential for airborne dispersal of Clostridium difficile from symptomatic patients. Clin Infect Dis. 2010;50:1450–7.

    Article  PubMed  Google Scholar 

  7. Johnson S, Kent SA, O’Leary KJ, et al. Fatal pseudomembranous colitis associated with a variant Clostridium difficile strain not detected by toxin A immunoassay. Ann Intern Med. 2001;135:434–8.

    PubMed  CAS  Google Scholar 

  8. Vaishnavi C, Bhasin D, Kochhar R, Singh K. Clostridium difficile toxin and faecal lactoferrin assays in adult patients. Microbes Infect. 2000;2:1827–30.

    Article  PubMed  CAS  Google Scholar 

  9. Tedesco FJ. Treatment of recurrent antibiotic-associated pseudomembranous colitis. Am J Gastroenterol. 1982;77:220–1.

    PubMed  CAS  Google Scholar 

  10. Gebhard RL, Gerding DN, Olson MM, et al. Clinical and endoscopic findings in patients early in the course of Clostridium difficile-associated pseudomembranous colitis. Am J Med. 1985;78:45–8.

    Article  PubMed  CAS  Google Scholar 

  11. Jafri SF, Marshall JB. Ascites associated with antibiotic-associated pseudomembranous colitis. South Med J. 1996;89:1014–7.

    Article  PubMed  CAS  Google Scholar 

  12. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care. 2007;13:450–5.

    Article  PubMed  Google Scholar 

  13. Tedesco FJ, Barton RW, Alpers DH. Clindamycin associated colitis. A prospective study. Ann Intern Med. 1974;81:429–33.

    PubMed  CAS  Google Scholar 

  14. Laine L. Management of acute colonic pseudo-obstruction. N Engl J Med. 1999;341:192–3.

    Article  PubMed  CAS  Google Scholar 

  15. Mahajan LA, Hupertz V, Mahajan S, et al. The appendix: a possible reservoir for Clostridium difficile. Am J Gastroenterol. 2006;101:S392.

    Google Scholar 

  16. 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;271:1913–8.

    Article  PubMed  CAS  Google Scholar 

  17. Kochhar R, Ayyagiri A, Goenka MK, Dhali GK, Aggarwal R, Mehta SK. Role of infectious agents in exacerbation of ulcerative colitis in India: a study of Clostridium difficile. J Clin Gastroenterol. 1993;16:26–30.

    Article  PubMed  CAS  Google Scholar 

  18. Vaishnavi C, Kochhar R, Bhasin DK, Thennarasu K, Singh K. Simultaneous assay for Clostridium difficile and fecal lactoferrin in ulcerative colitis. Trop Gastroenterol. 2003;24:13–6.

    PubMed  Google Scholar 

  19. Balamurugan R, Balaji V, Ramakrishna BS. Estimation of faecal carriage of Clostridium difficile in patients with ulcerative colitis using real time polymerase chain reaction. Indian J Med Res. 2008;127:472–7.

    PubMed  CAS  Google Scholar 

  20. Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol. 2009;15:1554–80.

    Article  PubMed  Google Scholar 

  21. Nguyen GC, Kaplan GG, Harris ML, Brant SR. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. 2008;103:1443–50.

    Article  PubMed  Google Scholar 

  22. Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:339–44.

    Article  PubMed  Google Scholar 

  23. Greenfield C, Aguilar Ramirez JR, Pounder RE, et al. Clostridium difficile and inflammatory bowel disease. Gut. 1983;24:713–7.

    Article  PubMed  CAS  Google Scholar 

  24. Issa M, Ananthakrishnan AN. Clostridium difficile and inflammatory bowel disease. Inflam Bowel Dis. 2008;14:1432–42.

    Article  Google Scholar 

  25. Gryboski JD. Clostridium difficile in inflammatory bowel disease relapse. J Pediatr Gastroenterol Nutr. 1991;13:39–41.

    Article  PubMed  CAS  Google Scholar 

  26. Boland E, Thompson JS. Fulminant Clostridium difficile enteritis after proctocolectomy and ileal pouch–anal anastomosis. Gastroenterol Res Pract. 2009;2008:1–5.

    Article  Google Scholar 

  27. Navaneethan U, Giannella RA. Thinking beyond the colon—small bowel involvement in Clostridium difficile infection. Gut Pathog. 2009;1:7.

    Article  PubMed  Google Scholar 

  28. Bhargava A, Sen P, Swaminathan A, Ogbolu C, Chechko S, Stone F. Rapidly progressive necrotizing fasciitis and gangrene due to Clostridium difficile. Clin Infect Dis. 2000;30:954–5.

    Article  PubMed  CAS  Google Scholar 

  29. Libby DB, Bearman G. Bacteremia due to Clostridium difficile—review of the literature. Int J Infect Dis. 2009:13: e305–9. Epub.

    Google Scholar 

  30. Fairweather SD, Youngs D, George RH, Burdon DW, Keighley MR. Arthritis in pseudomembranous colitis associated with an antibody to Clostridium difficile toxin. J R Soc Med. 1980;73:524–5.

    PubMed  CAS  Google Scholar 

  31. Boice JL. Reactive arthritis induced by Clostridium difficile. West J Med. 1994;160:171–2.

    PubMed  CAS  Google Scholar 

  32. Birnbaum J, Bartlett JG, Gelber AC. Clostridium difficile: an under recognized cause of reactive arthritis? Clin Rheumatol. 2008;27:253–5.

    Article  PubMed  Google Scholar 

  33. Jacobs A, Barnard K, Fishel R, Gradon JD. Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2001:80:88–101.

  34. Ducroix-Roubertou S, Genet C, Rogez JP, Weinbreck P, Denes E. Reactive arthritis due to Clostridium difficile. Med Mal Infect. 2005;35:419–21.

    Article  PubMed  CAS  Google Scholar 

  35. Brown TA, Rajappannair L, Dalton AB, Bandi R, Myers JP, Kefalas CH. Acute appendicitis in the setting of Clostridium difficile colitis: case report and review of the literature. Clin Gastroenterol Hepatol. 2007;5:969–71.

    Article  PubMed  Google Scholar 

  36. Price AB, Davies DR. Pseudomembranous colitis. J Clin Pathol. 1977;30:1–12.

    Article  PubMed  CAS  Google Scholar 

  37. Schnitt SJ, Antonioli DA, Goldman H. Massive mural edema in severe pseudomembranous colitis. Arch Pathol Lab Med. 1983;107:211–3.

    PubMed  CAS  Google Scholar 

  38. Vaishnavi C. Established and potential risk factors for Clostridium difficile infection. Indian J Med Microbiol. 2009;27:289–300.

    Article  PubMed  CAS  Google Scholar 

  39. Keven K, Basu A, Re L. Clostridium difficile colitis in patients after kidney and pancreas–kidney transplantation. Transpl Infect Dis. 2004;6:10–4.

    Article  PubMed  CAS  Google Scholar 

  40. Cunningham R, Dale B, Undy B, Gaunt N. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect. 2003;54:243–5.

    Article  PubMed  CAS  Google Scholar 

  41. Gellad ZF, Alexander BD, Liu JK, et al. Severity of Clostridium difficile-associated diarrhea in solid organ transplant patients. Transpl Infect Dis. 2007;9:276–80.

    Article  PubMed  CAS  Google Scholar 

  42. Zerey M, Paton BL, Lincourt AE, Gersin KS, Kercher KW, Heniford BT. The burden of Clostridium difficile in surgical patients in the United States. Surg Infect (Larchmt). 2007;8:557–66.

    Article  Google Scholar 

  43. Weiss B, Kleinkauf N, Neumann M, et al. Risk factors for Clostridium difficile ribotype 027 infection in Germany: preliminary results of a retrospective case–control study (abstract). 18th European Congress of Clin. Microbial and Infectious Diseases, Barcelona, Spain. 2008:1480.

  44. Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease:old therapies and new strategies. Lancet Infect Dis. 2005;5:549–57.

    Article  PubMed  CAS  Google Scholar 

  45. Pepin J, Saheb N, Coulombe M, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhoea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41:1254–60.

    Article  PubMed  CAS  Google Scholar 

  46. Keel K, Brazier JS, Post KW, Weese S, Songer JG. Prevalence of PCR ribotypes among Clostridium difficile isolates from pigs, calves, and other species. J Clin Microbiol. 2007;45:1963–4.

    Article  PubMed  CAS  Google Scholar 

  47. Gupta U, Jadav RN. Clostridium difficile in hospital patients. Indian J Med Res. 1985;82:398–401.

    PubMed  CAS  Google Scholar 

  48. Ayyagari A, Sharma P, Venkateswarlu, Mehta S, Agarwal KC. Prevalence of Clostridium difficile in pseudomembranous and antibiotic associated colitis in North India. J Diarrhoeal Dis Res. 1986;4:157–60.

    PubMed  CAS  Google Scholar 

  49. Niyogi SK, Dutta P, Dutta D, Mitra U, Sikdar S. Clostridium difficile and its cytotoxin in hospitalized children with acute diarrhea. Indian Pediatr. 1991;28:1129–32.

    PubMed  CAS  Google Scholar 

  50. Niyogi SK, Bhattacharya SK, Dutta P, et al. Prevalence of Clostridium difficile in hospitalised patients with acute diarrhoea in Calcutta. J Diarrhoeal Dis Res. 1991;9:16–9.

    PubMed  CAS  Google Scholar 

  51. Bhattacharya MK, Niyogi SK, Rasaily R, et al. Clinical manifestation of Clostridium difficile enteritis in Calcutta. J Assoc Physicians India. 1991;39:683–4.

    PubMed  CAS  Google Scholar 

  52. Vaishnavi C, Kochhar R, Bhasin DK, Thapa BR, Singh K. Detection of Clostridium difficile toxin by an indigenously developed latex agglutination assay. Trop Gastroenterol. 1999;20:33–5.

    PubMed  CAS  Google Scholar 

  53. Vaishnavi C, Kochhar R, Bhasin DK, et al. Faecal lactoferrin latex agglutination assay for Clostridium difficile associated intestinal disease. Indian J Med Microbiol. 1998;16:81–3.

    Google Scholar 

  54. Kang G, Srivastava A, Pulimood AB, Dennison D, Chandy M. Etiology of diarrhea in patients undergoing allogenic bone marrow transplantation in South India. Transplantation. 2002;73:1247–51.

    Article  PubMed  Google Scholar 

  55. Kumar B, Vaishnavi C, Sandhu K, Kaur I. Clostridium difficile toxin assay in psoriatic patients. Trop Gastroenterol. 2004;25:164–7.

    PubMed  Google Scholar 

  56. Gogate A, De A, Nanivadekar R, et al. Diagnostic role of stool culture and toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children. Indian J Med Res. 2005;122:518–24.

    PubMed  CAS  Google Scholar 

  57. Chaudhry R, Joshy L, Kumar L, Dhawan B. Changing pattern of Clostridium difficile associated diarrhoea in a tertiary care hospital: a 5 year retrospective study. Indian J Med Res. 2008;127:377–82.

    PubMed  Google Scholar 

  58. Ingle M, Deshmukh A, Desai D, et al. Prevalence and clinical course of Clostridium difficile infection in a tertiary-care hospital: a retrospective analysis. Indian J Gastroenterol. 2011;30:89–93.

    Article  PubMed  Google Scholar 

  59. Teasley PG, Gerding DN, Olson MM, et al. Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhea and colitis. Lancet. 1983;2:1043–6.

    Article  PubMed  CAS  Google Scholar 

  60. Bauer MP, van Dissel JT, Kuijper EJ. Clostridium difficile: controversies and approaches to management. Curr Opin Infect Dis. 2009;22:517–24.

    Article  PubMed  Google Scholar 

  61. Ben-Horin S, Margalit M, Bossuyt P, et al. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and Clostridium difficile infection. Clin Gastroenterol Hepatol. 2009;7:981–7.

    Article  PubMed  Google Scholar 

  62. Enache-Angoulvant A, Hemnnequin C. Invasive Saccharmyces infection: a comprehensive review. Clin Infect Dis. 2005;41:1559–68.

    Article  PubMed  Google Scholar 

  63. Park J, Floch MH. Prebiotics, probiotics and dietary fiber in gastrointestinal diseases. Gastroenterol Clin North Am. 2007;36:47–63.

    Article  PubMed  Google Scholar 

  64. Lewis S, Burmeister S, Brazier J. Effect of prebiotic oligofructose on relapse of Clostridium difficile associated diarrhea: a randomized, controlled study. Clin Gastroenterol Hepatol. 2005;3:442–8.

    Article  PubMed  CAS  Google Scholar 

  65. Jorup-Ronstrom C, Hakonson A, Persson AK, Midtvedt T, Norin E. Feces culture successful therapy in Clostridium difficile diarrhea. Lakartidningen (Swedish). 2006;103:3603–5.

    PubMed  Google Scholar 

  66. Louie RJ, Peppe J, Watt CK, et al. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile associated diarrhea. Clin Infect Dis. 2006;43:411–20.

    Article  PubMed  CAS  Google Scholar 

  67. Balagopal A, Sears CL. Clostridium difficile: new therapeutic options. Curr Opin Pharmacol. 2007;7:455–8.

    Article  PubMed  CAS  Google Scholar 

  68. Leung DY, Kelly CP, Bogunlewicz M, Pothoulakis C, LaMont JT, Flores A. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr. 1991;118:633–7.

    Article  PubMed  CAS  Google Scholar 

  69. Abougergi MS, Broor A, Cui W, Jaar BG. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature. J Hospital Med. 2010;5:E1–9.

    Article  Google Scholar 

  70. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362:197–205.

    Article  PubMed  CAS  Google Scholar 

  71. van Dissel JT, Groot ND, Hensgens MH, et al. Bovine antibody enriched whey to aid in the prevention of a relapse of Clostridium difficile associated diarrhea: preclinical and preliminary clinical data. J Med Microbiol. 2005;54:197–205.

    Article  PubMed  Google Scholar 

  72. Aboudala S, Kotloff KL, Kyne L, et al. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun. 2003;71:1608–10.

    Article  Google Scholar 

  73. Souigioltzis S, Kyne L, Drudy D, et al. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology. 2005;128:764–70.

    Article  Google Scholar 

  74. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis. 2006;43:421–7.

    Article  PubMed  CAS  Google Scholar 

  75. Herpers BL, Vlaminckx B, Burkhardt O, et al. Intravenous tigecycline as adjunctive or alternate therapy for severe refractory Clostridium difficile infection. Clin Infect Dis. 2009;48:1732–5.

    Article  PubMed  CAS  Google Scholar 

  76. Louie TJ, Miller MA, Mullane KM. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–31.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, Punjab, India

    Chetana Vaishnavi

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Vaishnavi, C. Clostridium difficile infection: clinical spectrum and approach to management. Indian J Gastroenterol 30, 245–254 (2011). https://doi.org/10.1007/s12664-011-0148-y

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