1932

Abstract

infection (CDI) is a serious complication of hospitalization and antibiotic use with a high mortality and very high costs. Despite appropriate treatment, a subset of patients develop chronic recurrent CDI. Some other patients develop severe and life-threatening colitis. The risk factors, pathogenesis, and treatment of recurrent CDI and severe CDI are discussed in this review. In particular, fecal microbiota transplantation (FMT) as a treatment strategy is outlined and a treatment algorithm incorporating FMT is described.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-070813-114317
2015-01-14
2024-10-11
Loading full text...

Full text loading...

/deliver/fulltext/med/66/1/annurev-med-070813-114317.html?itemId=/content/journals/10.1146/annurev-med-070813-114317&mimeType=html&fmt=ahah

Literature Cited

  1. Hensgens MP, Goorhuis A, Dekkers OM. 1.  et al. 2013. All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study. Clin. Infect. Dis. 56:81108–16 [Google Scholar]
  2. Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. 2.  2012. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J. Antimicrob. Chemother. 67:3742–48 [Google Scholar]
  3. Khanna S, Pardi DS, Aronson SL. 3.  et al. 2012. The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am. J. Gastroenterol. 107:189–95 [Google Scholar]
  4. Soes LM, Holt HM, Bottiger B. 4.  et al. 2014. The incidence and clinical symptomatology of Clostridium difficile infections in a community setting in a cohort of Danish patients attending general practice. Eur. J. Clin. Microbiol. Infect. Dis. 33:6957–67 [Google Scholar]
  5. Hensgens MP, Dekkers OM, Demeulemeester A. 5.  et al. 2014. Diarrhoea in general practice: When should a Clostridium difficile infection be considered? Results of a nested case-control study. Clin. Microbiol. Infect. In press. doi: 10.1111/1469-0691.12758 [Google Scholar]
  6. Bauer MP, Veenendaal D, Verhoef L. 6.  et al. 2009. Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands. Clin. Microbiol. Infect. 15:121087–92 [Google Scholar]
  7. Debast SB, Bauer MP, Kuijper EJ. 7.  2014. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin. Microbiol. Infect. 20:Suppl. 21–26 [Google Scholar]
  8. Hu MY, Katchar K, Kyne L. 8.  et al. 2009. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 136:41206–14 [Google Scholar]
  9. Hensgens MP, Dekkers OM, Goorhuis A. 9.  et al. 2013. Predicting a complicated course of Clostridium difficile infection at the bedside. Clin. Microbiol. Infect. 20:5O301–8 [Google Scholar]
  10. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. 10.  2010. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J. Clin. Gastroenterol. 44:5354–60 [Google Scholar]
  11. van Nood E, Vrieze A, Nieuwdorp M. 11.  et al. 2013. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368:5407–15 [Google Scholar]
  12. Dethlefsen L, Huse S, Sogin ML, Relman DA. 12.  2008. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLOS Biol. 6:11e280 [Google Scholar]
  13. Chang JY, Antonopoulos DA, Kalra A. 13.  et al. 2008. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile–associated diarrhea. J. Infect. Dis. 197:3435–38 [Google Scholar]
  14. Fuentes S, van Nood E, Tims S. 14.  et al. 2014. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection. ISME J. 8:1621–33 [Google Scholar]
  15. Song Y, Garg S, Girotra M. 15.  et al. 2013. Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection. PLOS ONE 8:11e81330 [Google Scholar]
  16. Britton RA, Young VB. 16.  2014. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology 146:61547–53 [Google Scholar]
  17. Khosravi A, Mazmanian SK. 17.  2013. Disruption of the gut microbiome as a risk factor for microbial infections. Curr. Opin. Microbiol. 16:2221–27 [Google Scholar]
  18. Antunes LC, Han J, Ferreira RB. 18.  et al. 2011. Effect of antibiotic treatment on the intestinal metabolome. Antimicrob. Agents Chemother. 55:41494–503 [Google Scholar]
  19. Giel JL, Sorg JA, Sonenshein AL, Zhu J. 19.  2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLOS ONE 5:1e8740 [Google Scholar]
  20. Weingarden AR, Chen C, Bobr A. 20.  et al. 2014. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol. 306:4G310–19 [Google Scholar]
  21. Rea MC, Sit CS, Clayton E. 21.  et al. 2010. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. Proc. Natl. Acad. Sci. USA 107:209352–57 [Google Scholar]
  22. Johnston BC, Ma SS, Goldenberg JZ. 22.  et al. 2012. Probiotics for the prevention of Clostridium difficile–associated diarrhea: a systematic review and meta-analysis. Ann. Intern. Med. 157:12878–88 [Google Scholar]
  23. McFarland LV.23.  2006. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am. J. Gastroenterol. 101:4812–22 [Google Scholar]
  24. Allen SJ, Wareham K, Wang D. 24.  et al. 2013. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 382:99001249–57 [Google Scholar]
  25. Hensgens MP, Keessen EC, Squire MM. 25.  et al. 2012. Clostridium difficile infection in the community: a zoonotic disease?. Clin. Microbiol. Infect. 18:7635–45 [Google Scholar]
  26. Alam MJ, Anu A, Walk ST, Garey KW. 26.  2014. Investigation of potentially pathogenic Clostridium difficile contamination in household environs. Anaerobe 27:31–33 [Google Scholar]
  27. Kato H, Kita H, Karasawa T. 27.  et al. 2001. Colonisation and transmission of Clostridium difficile in healthy individuals examined by PCR ribotyping and pulsed-field gel electrophoresis. J. Med. Microbiol. 50:8720–27 [Google Scholar]
  28. Ozaki E, Kato H, Kita H. 28.  et al. 2004. Clostridium difficile colonization in healthy adults: transient colonization and correlation with enterococcal colonization. J. Med. Microbiol. 53:Pt. 2167–72 [Google Scholar]
  29. Kyne L, Warny M, Qamar A, Kelly CP. 29.  2000. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N. Engl. J. Med. 342:6390–97 [Google Scholar]
  30. Johnson S, Gerding DN. 30.  1998. Clostridium difficile–associated diarrhea. Clin. Infect. Dis. 26:1027–36 [Google Scholar]
  31. Arvand M, Moser V, Schwehn C. 31.  et al. 2012. High prevalence of Clostridium difficile colonization among nursing home residents in Hesse, Germany. PLOS ONE 7:1e30183 [Google Scholar]
  32. Riggs MM, Sethi AK, Zabarsky TF. 32.  et al. 2007. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin. Infect. Dis. 45:8992–98 [Google Scholar]
  33. Rea MC, O'Sullivan O, Shanahan F. 33.  et al. 2012. Clostridium difficile carriage in elderly subjects and associated changes in the intestinal microbiota. J. Clin. Microbiol. 50:3867–75 [Google Scholar]
  34. Eyre DW, Cule ML, Wilson DJ. 34.  et al. 2013. Diverse sources of C. difficile infection identified on whole-genome sequencing. N. Engl. J. Med. 369:131195–205 [Google Scholar]
  35. Kamboj M, Khosa P, Kaltsas A. 35.  et al. 2011. Relapse versus reinfection: surveillance of Clostridium difficile infection. Clin. Infect. Dis. 53:101003–6 [Google Scholar]
  36. Bauer MP, Nibbering PH, Poxton IR. 36.  et al. 2014. Humoral immune response as predictor of recurrence in Clostridium difficile infection. Clin. Microbiol. In press. doi: 10.1111/1469-0691.12769 [Google Scholar]
  37. Kyne L, Warny M, Qamar A, Kelly CP. 37.  2001. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357:9251189–93 [Google Scholar]
  38. Shim JK, Johnson S, Samore MH. 38.  et al. 1998. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 351:9103633–36 [Google Scholar]
  39. Tschudin Sutter S, Carroll KC, Tamma PD. 39.  et al. 2014. Clostridium difficile: impact of colonisation versus transmission on the development of infection—results from a prospective observational study Poster 0073. Presented at Eur. Congr. Clin. Microbiol. Infect. Dis., 10–14 May, Barcelona, Spain [Google Scholar]
  40. Lowy I, Molrine DC, Leav BA. 40.  et al. 2010. Treatment with monoclonal antibodies against Clostridium difficile toxins. N. Engl. J. Med. 362:3197–205 [Google Scholar]
  41. Mattila E, Anttila VJ, Broas M. 41.  et al. 2008. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile–associated diarrhoea: efficacy and safety data of a prematurely interrupted trial. Scand. J. Infect. Dis. 40:9702–8 [Google Scholar]
  42. Numan SC, Veldkamp P, Kuijper EJ. 42.  et al. 2007. Clostridium difficile–associated diarrhoea: bovine anti–Clostridium difficile whey protein to help aid the prevention of relapses. Gut 56:6888–89 [Google Scholar]
  43. Bartlett JG, Chang TW, Gurwith M. 43.  et al. 1978. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N. Engl. J. Med. 298:10531–34 [Google Scholar]
  44. Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ. 44.  2009. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile–infection (CDI). Clin. Microbiol. Infect. 15:121053–66 [Google Scholar]
  45. Surawicz CM, Brandt LJ, Binion DG. 45.  et al. 2013. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am. J. Gastroenterol. 108:4478–98 [Google Scholar]
  46. Deshpande A, Pasupuleti V, Rolston DD. 46.  et al. 2011. Diagnostic accuracy of real-time polymerase chain reaction in detection of Clostridium difficile in the stool samples of patients with suspected Clostridium difficile infection: a meta-analysis. Clin. Infect. Dis. 53:7e81–e90 [Google Scholar]
  47. Cornely OA, Crook DW, Esposito R. 47.  et al. 2012. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect. Dis. 12:4281–89 [Google Scholar]
  48. Louie TJ, Miller MA, Mullane KM. 48.  et al. 2011. Fidaxomicin versus vancomycin for Clostridium difficile infection. N. Engl. J. Med. 364:5422–31 [Google Scholar]
  49. Nelson RL, Kelsey P, Leeman H. 49.  et al. 2011. Antibiotic treatment for Clostridium difficile–associated diarrhea in adults. Cochrane Database Syst. Rev.9CD004610 [Google Scholar]
  50. van Nood E, Keller JJ, Kuijper EJ, Speelman P. 50.  2013. Nieuwe mogelijkheden bij Clostridium difficile-infecties [New treatment options for infections with Clostridium difficile]. Ned. Tijdschr. Geneeskd. 157:48A6580 [Google Scholar]
  51. Debast SB, Bauer MP, Sanders IM. 51.  et al. 2013. Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications. J. Antimicrob. Chemother. 68:61305–11 [Google Scholar]
  52. Scott LJ.52.  2013. Fidaxomicin: a review of its use in patients with Clostridium difficile infection. Drugs 73:151733–47 [Google Scholar]
  53. Louie TJ, Cannon K, Byrne B. 53.  et al. 2012. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin. Infect. Dis. 55:Suppl. 2S132–42 [Google Scholar]
  54. Iarikov DE, Alexander J, Nambiar S. 54.  2014. Hypersensitivity reactions associated with fidaxomicin use. Clin. Infect. Dis. 58:4537–39 [Google Scholar]
  55. Smeltzer S, Hassoun A. 55.  2013. Successful use of fidaxomicin in recurrent Clostridium difficile infection in a child. J. Antimicrob. Chemother. 68:71688–89 [Google Scholar]
  56. Eiseman B, Silen W, Bascom GS, Kauvar AJ. 56.  1958. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44:5854–59 [Google Scholar]
  57. Gough E, Shaikh H, Manges AR. 57.  2011. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin. Infect. Dis. 53:10994–1002 [Google Scholar]
  58. van Nood E, Speelman P, Kuijper EJ, Keller JJ. 58.  2009. Struggling with recurrent Clostridium difficile infections: Is donor faeces the solution?. Eurosurveillance 14:3419316 [Google Scholar]
  59. Owens C, Broussard E, Surawicz C. 59.  2013. Fecal microbiota transplantation and donor standardization. Trends Microbiol. 21:443–45 [Google Scholar]
  60. Bakken JS, Borody T, Brandt LJ. 60.  et al. 2011. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. 9:121044–49 [Google Scholar]
  61. Lee CH, Belanger JE, Kassam Z. 61.  et al. 2014. The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur. J. Clin. Microbiol. Infect. Dis. 33:81425–28 [Google Scholar]
  62. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. 62.  2012. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am. J. Gastroenterol. 107:5761–67 [Google Scholar]
  63. Youngster I, Sauk J, Pindar C. 63.  et al. 2014. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin. Infect. Dis. 58:111515–22 [Google Scholar]
  64. Louie TJ. 64.  et al. 2013. Fecal microbiome transplantation (FMT) via oral fecal microbial capsules for recurrent Clostridium difficile infection (rCDI) Presented at ID Week, Oct. 8–12, Philadelphia, PA. Abstr. 89 [Google Scholar]
  65. Quera R, Espinoza R, Estay C, Rivera D. 65.  2014. Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn's disease and recurrent Clostridium difficile infection. J. Crohn's Colitis 8:3252–53 [Google Scholar]
  66. Angelberger S, Reinisch W, Makristathis A. 66.  et al. 2013. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am. J. Gastroenterol. 108:1620–30 [Google Scholar]
  67. Kelly CR, Ihunnah C, Fischer M. 67.  et al. 2014. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am. J. Gastroenterol. 109:1065–71 [Google Scholar]
  68. Tvede M, Rask-Madsen J. 68.  1989. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 333:86481156–60 [Google Scholar]
  69. Petrof EO, Gloor GB, Vanner SJ. 69.  et al. 2013. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: “RePOOPulating” the gut. Microbiome 1:3 [Google Scholar]
  70. Besselink MG, van Santvoort HC, Buskens E. 70.  et al. 2008. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:9613651–59 [Google Scholar]
  71. Juang P, Skledar SJ, Zgheib NK. 71.  et al. 2007. Clinical outcomes of intravenous immune globulin in severe clostridium difficile–associated diarrhea. Am. J. Infect. Control 35:2131–37 [Google Scholar]
  72. Abougergi MS, Broor A, Cui W, Jaar BG. 72.  2010. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature. J. Hosp. Med. 5:1E1–E9 [Google Scholar]
  73. Seltman AK.73.  2012. Surgical management of Clostridium difficile colitis. Clin. Colon Rectal Surg. 25:4204–9 [Google Scholar]
  74. Neal MD, Alverdy JC, Hall DE. 74.  et al. 2011. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann. Surg. 254:3423–27 [Google Scholar]
  75. Brandt LJ, Borody TJ, Campbell J. 75.  2011. Endoscopic fecal microbiota transplantation: “first-line” treatment for severe clostridium difficile infection?. J. Clin. Gastroenterol. 45:8655–57 [Google Scholar]
  76. You DM, Franzos MA, Holman RP. 76.  2008. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann. Intern. Med. 148:8632–33 [Google Scholar]
  77. Neemann K, Eichele DD, Smith PW. 77.  et al. 2012. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient. Transpl. Infect. Dis. 14:6E161–65 [Google Scholar]
/content/journals/10.1146/annurev-med-070813-114317
Loading
/content/journals/10.1146/annurev-med-070813-114317
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error