Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

Clostridium difficile infection in children: Treatment and outcome

Jonathan Crews, MD, MS
Section Editor
Sheldon L Kaplan, MD
Deputy Editor
Mary M Torchia, MD


Clostridium difficile is an important cause of antibiotic-associated diarrhea and one of the most common healthcare-associated infections [1]. It causes a wide spectrum of illnesses from asymptomatic colonization or mild diarrhea to fulminant disease characterized by toxic megacolon, sepsis, and death. C. difficile infection is less common in children than adults, but the incidence of C. difficile infection in children is increasing [2-5].

The treatment of and outcomes associated with C. difficile infection in children will be discussed here. The pathogenesis, epidemiology, clinical features, diagnosis, and prevention of C. difficile are discussed separately. (See "Clostridium difficile infection in children: Microbiology, pathogenesis, and epidemiology" and "Clostridium difficile infection in children: Clinical features and diagnosis" and "Clostridium difficile infection: Prevention and control".)

C. difficile infection in adults also is discussed separately. (See "Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology" and "Clostridium difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridium difficile in adults: Treatment".)

There is limited high-quality evidence to guide the management of pediatric C. difficile infection. Most treatment recommendations are extrapolated from studies performed in adults. The treatment guidelines presented below are largely compatible with the recommendations of the American Academy of Pediatrics Committee on Infectious Diseases (2013), the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America guidelines for the treatment of C. difficile in adults (2010), and the American College of Gastroenterology (2013) [6-8].


Discontinuation of inciting antibiotics — Discontinuation of the inciting antibiotic is important in the management of C. difficile infection [6-8]. The use of concomitant antibiotics (ie, antibiotics other than those used to treat C. difficile) during treatment for C. difficile infection has been shown to prolong the duration of symptoms and increase the risk of recurrence in adults [9,10]. In children, the use of concomitant antibiotics has been associated with recurrent disease [11]. If an ongoing infection requires continued antibiotic treatment, we suggest tailoring therapy to achieve the narrowest spectrum and shortest duration possible   (See "Clostridium difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Antibiotic exposure'.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2015. | This topic last updated: Aug 25, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
  1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372:825.
  2. Kim J, Smathers SA, Prasad P, et al. Epidemiological features of Clostridium difficile-associated disease among inpatients at children's hospitals in the United States, 2001-2006. Pediatrics 2008; 122:1266.
  3. Nylund CM, Goudie A, Garza JM, et al. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011; 165:451.
  4. Zilberberg MD, Tillotson GS, McDonald C. Clostridium difficile infections among hospitalized children, United States, 1997-2006. Emerg Infect Dis 2010; 16:604.
  5. Deshpande A, Pant C, Anderson MP, et al. Clostridium difficile infection in the hospitalized pediatric population: increasing trend in disease incidence. Pediatr Infect Dis J 2013; 32:1138.
  6. Schutze GE, Willoughby RE, Committee on Infectious Diseases, American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics 2013; 131:196.
  7. 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.
  8. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108:478.
  9. Dubberke ER, Yan Y, Reske KA, et al. Development and validation of a Clostridium difficile infection risk prediction model. Infect Control Hosp Epidemiol 2011; 32:360.
  10. Mullane KM, Miller MA, Weiss K, et al. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis 2011; 53:440.
  11. Tschudin-Sutter S, Tamma PD, Milstone AM, Perl TM. Predictors of first recurrence of Clostridium difficile infections in children. Pediatr Infect Dis J 2014; 33:414.
  12. Morinville V, McDonald J. Clostridium difficile-associated diarrhea in 200 Canadian children. Can J Gastroenterol 2005; 19:497.
  13. Gogate A, De A, Nanivadekar R, et al. Diagnostic role of stool culture & toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children. Indian J Med Res 2005; 122:518.
  14. Shannon-Lowe J, Matheson NJ, Cooke FJ, Aliyu SH. Prevention and medical management of Clostridium difficile infection. BMJ 2010; 340:c1296.
  15. Church JM, Fazio VW. A role for colonic stasis in the pathogenesis of disease related to Clostridium difficile. Dis Colon Rectum 1986; 29:804.
  16. Koo HL, Koo DC, Musher DM, DuPont HL. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis 2009; 48:598.
  17. American Academy of Pediatrics. Clostridium difficile. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.298.
  18. Vasa CV, Glatt AE. Effectiveness and appropriateness of empiric metronidazole for Clostridium difficile-associated diarrhea. Am J Gastroenterol 2003; 98:354.
  19. Johnson S, Homann SR, Bettin KM, et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117:297.
  20. Wenisch 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.
  21. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45:302.
  22. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet 1983; 2:1043.
  23. Nelson RL, Kelsey P, Leeman H, et al. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2011; :CD004610.
  24. Al-Nassir WN, Sethi AK, Li Y, et al. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother 2008; 52:2403.
  25. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis 2014; 59:345.
  26. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut 1986; 27:1169.
  27. Baines SD, O'Connor R, Freeman J, et al. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. J Antimicrob Chemother 2008; 62:1046.
  28. Peláez T, Alcalá L, Alonso R, et al. Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrob Agents Chemother 2002; 46:1647.
  29. Mergenhagen KA, Wojciechowski AL, Paladino JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics 2014; 32:639.
  30. Bass SN, Lam SW, Bauer SR, Neuner EA. Comparison of oral vancomycin capsule and solution for treatment of initial episode of severe Clostridium difficile Infection. J Pharm Pract 2015; 28:183.
  31. Pai S, Aliyu SH, Enoch DA, Karas JA. Five years experience of Clostridium difficile infection in children at a UK tertiary hospital: proposed criteria for diagnosis and management. PLoS One 2012; 7:e51728.
  32. Tschudin-Sutter S, Tamma PD, Milstone AM, Perl TM. The prediction of complicated Clostridium difficile infections in children. Infect Control Hosp Epidemiol 2014; 35:901.
  33. Schwartz KL, Darwish I, Richardson SE, et al. Severe clinical outcome is uncommon in Clostridium difficile infection in children: a retrospective cohort study. BMC Pediatr 2014; 14:28.
  34. Khanna S, Baddour LM, Huskins WC, et al. The epidemiology of Clostridium difficile infection in children: a population-based study. Clin Infect Dis 2013; 56:1401.
  35. Crews JD, Koo HL, Jiang ZD, et al. A hospital-based study of the clinical characteristics of Clostridium difficile infection in children. Pediatr Infect Dis J 2014; 33:924.
  36. Wood A, Wassil K, Edwards E. Oral Absorption of Enteral Vancomycin in a Child with Clostridium difficile Colitis and Renal Impairment. J Pediatr Pharmacol Ther 2013; 18:315.
  37. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 2005; 40:1586.
  38. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005; 40:1591.
  39. Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis 2005; 5:549.
  40. Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med 2015; 372:1539.
  41. Apisarnthanarak A, Khoury H, Reinus WR, et al. Severe Clostridium difficile colitis: the role of intracolonic vancomycin? Am J Med 2002; 112:328.
  42. Wenisch JM, Schmid D, Kuo HW, et al. Prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection. Antimicrob Agents Chemother 2012; 56:1974.
  43. Saffouri G, Khanna S, Estes L, Pardi D. Outcomes from rectal vancomycin therapy in patients with Clostridium difficile infection. Am J Gastroenterol 2014; 109:924.
  44. Lee J, Tashjian DB, Moriarty KP. Is partial colectomy the operation of choice in pediatric Clostridium difficile colitis? Pediatr Surg Int 2012; 28:603.
  45. Castillo A, López J, Panadero E, et al. Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient. Transpl Infect Dis 2012; 14:E34.
  46. Bartlett JG. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1984; 6 Suppl 1:S235.
  47. Al-Nassir WN, Sethi AK, Nerandzic MM, et al. Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008; 47:56.
  48. Kociolek LK, Patel SJ, Shulman ST, Gerding DN. Molecular epidemiology of Clostridium difficile infections in children: a retrospective cohort study. Infect Control Hosp Epidemiol 2015; 36:445.
  49. Kim J, Shaklee JF, Smathers S, et al. Risk factors and outcomes associated with severe clostridium difficile infection in children. Pediatr Infect Dis J 2012; 31:134.
  50. McDonald LC, Coignard B, Dubberke E, et al. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007; 28:140.
  51. Kato H, Kato N, Watanabe K, et al. Relapses or reinfections: analysis of a case of Clostridium difficile-associated colitis by two typing systems. Curr Microbiol 1996; 33:220.
  52. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 2001; 357:189.
  53. Garey KW, Jiang ZD, Ghantoji S, et al. A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection. Clin Infect Dis 2010; 51:1406.
  54. Nicholson MR, Thomsen IP, Slaughter JC, et al. Novel risk factors for recurrent Clostridium difficile infection in children. J Pediatr Gastroenterol Nutr 2015; 60:18.
  55. Sammons JS, Gerber JS, Tamma PD, et al. Diagnosis and management of Clostridium difficile infection by pediatric infectious diseases physicians. J Pediatric Infect Dis Soc 2013; 4:43.
  56. Tamma PD, Sandora TJ. Clostridium difficile Infection in Children: Current State and Unanswered Questions. J Pediatric Infect Dis Soc 2012; 1:230.
  57. McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 2002; 97:1769.
  58. Dificid (Fidaxomicin) prescribing information www.accessdata.fda.gov/drugsatfda_docs/label/2011/201699s000lbl.pdf (Accessed on March 26, 2015).
  59. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364:422.
  60. Cornely OA, Crook DW, Esposito R, et al. 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 2012; 12:281.
  61. Crook DW, Walker AS, Kean Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis 2012; 55 Suppl 2:S93.
  62. Sears P, Kaplan SL, Michaels M, Flanagan S, O'Gorman M. Safety and pharmacokinetic study of fidaxomicin in children with Clostridium difficile-associated diarrhea. Abstract and oral presentation, ID Week, Philadelphia, PA, October 2014. https://idsa.confex.com/idsa/2014/webprogram/Paper48416.html (Accessed on April 30, 2015).
  63. ClinicalTrials.gov. A study to investigate the safety and efficacy of fidaxomicin (oral suspension or tablets and vancomycin (oral liquid or capsules) in pediatric subjects with Clostridium difficile-associated diarrhea (CDAD). https://clinicaltrials.gov/ct2/show/NCT02218372 (Accessed on April 30, 2015).
  64. Gerard L, Garey KW, DuPont HL. Rifaximin: a nonabsorbable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert Rev Anti Infect Ther 2005; 3:201.
  65. Mattila E, Arkkila P, Mattila PS, et al. Rifaximin in the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2013; 37:122.
  66. Patrick Basu P, Dinani A, Rayapudi K, et al. Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial. Therap Adv Gastroenterol 2010; 3:221.
  67. Curry SR, Marsh JW, Shutt KA, et al. High frequency of rifampin resistance identified in an epidemic Clostridium difficile clone from a large teaching hospital. Clin Infect Dis 2009; 48:425.
  68. Miller MA, Blanchette R, Spigaglia P, et al. Divergent rifamycin susceptibilities of Clostridium difficile strains in Canada and Italy and predictive accuracy of rifampin Etest for rifamycin resistance. J Clin Microbiol 2011; 49:4319.
  69. Dubreuil L, Houcke I, Mouton Y, Rossignol JF. In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrob Agents Chemother 1996; 40:2266.
  70. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis 2006; 43:421.
  71. Musher DM, Logan N, Bressler AM, et al. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clin Infect Dis 2009; 48:e41.
  72. Musher DM, Logan N, Mehendiratta V, et al. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother 2007; 59:705.
  73. Cavalcanti AB, Goncalves AR, Almeida CS, et al. Teicoplanin versus vancomycin for proven or suspected infection. Cochrane Database Syst Rev 2010; :CD007022.
  74. Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013; 108:500.
  75. Youngster I, Russell GH, Pindar C, et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014; 312:1772.
  76. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013; 368:407.
  77. Kronman MP, Nielson HJ, Adler AL, et al. Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients. J Pediatr Gastroenterol Nutr 2015; 60:23.
  78. Russell G, Kaplan J, Ferraro M, Michelow IC. Fecal bacteriotherapy for relapsing Clostridium difficile infection in a child: a proposed treatment protocol. Pediatrics 2010; 126:e239.
  79. Kahn SA, Young S, Rubin DT. Colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection in a child. Am J Gastroenterol 2012; 107:1930.
  80. Pierog A, Mencin A, Reilly NR. Fecal microbiota transplantation in children with recurrent Clostridium difficile infection. Pediatr Infect Dis J 2014; 33:1198.
  81. ClinicalTrials.gov. Fecal Transplant for Pediatric Patients Who Have Recurrent C-diff Infection (NCT02134392). https://clinicaltrials.gov/ct2/show/NCT02134392 (Accessed on April 07, 2015).
  82. ClinicalTrials.gov. Stool Transplant in Pediatric Patients With Recurring C. Difficile Infection (NCT01972334) https://clinicaltrials.gov/ct2/show/NCT01972334 (Accessed on April 07, 2015).
  83. Sammons JS, Localio R, Xiao R, et al. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis 2013; 57:1.
  84. Vendetti N, Zaoutis T, Coffin SE, Sammons JS. Risk Factors for In-Hospital Mortality among a Cohort of Children with Clostridium difficile Infection. Infect Control Hosp Epidemiol 2015; :1.