UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Clostridium difficile infection in children: Microbiology, pathogenesis, and epidemiology

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

INTRODUCTION

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 microbiology, pathogenesis, and epidemiology of C. difficile infection in children will be discussed below. The clinical features, diagnosis, treatment, and prevention of C. difficile infection in children are discussed separately. (See "Clostridium difficile infection in children: Clinical features and diagnosis" and "Clostridium difficile infection in children: Treatment and outcome" 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".)

MICROBIOLOGY

Organism — C. difficile is an anaerobic, Gram-positive, spore-forming, toxin-producing bacillus. It exists in spore form in the environment. The spores are metabolically dormant and resistant to heat, acid, antibiotics, and most disinfectants. Once C. difficile spores reach the intestine, they germinate into the vegetative form, which is capable of producing toxins and is susceptible to killing by antimicrobial agents.

C. difficile is widely distributed in nature. It has been found in water, soil, food products (vegetables and retail meat), farm animals, and households [6-10]. Within healthcare facilities, C. difficile has been cultured from the hands of patients and healthcare personnel, hospital surfaces, medical equipment, and hospital pet therapy dogs [11,12]. C. difficile can persist on hospital surfaces for months [11].

                 

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: Nov 2016. | This topic last updated: Thu Sep 08 00:00:00 GMT+00:00 2016.
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 ©2016 UpToDate, Inc.
References
Top
  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. Zilberberg MD, Tillotson GS, McDonald C. Clostridium difficile infections among hospitalized children, United States, 1997-2006. Emerg Infect Dis 2010; 16:604.
  4. 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.
  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. Rodriguez-Palacios A, Staempfli HR, Duffield T, Weese JS. Clostridium difficile in retail ground meat, Canada. Emerg Infect Dis 2007; 13:485.
  7. Bauer MP, Kuijper EJ. Potential sources of Clostridium difficile in human infection. Infect Dis Clin North Am 2015; 29:29.
  8. Bakri MM, Brown DJ, Butcher JP, Sutherland AD. Clostridium difficile in ready-to-eat salads, Scotland. Emerg Infect Dis 2009; 15:817.
  9. Koene MG, Mevius D, Wagenaar JA, et al. Clostridium difficile in Dutch animals: their presence, characteristics and similarities with human isolates. Clin Microbiol Infect 2012; 18:778.
  10. Alam MJ, Anu A, Walk ST, Garey KW. Investigation of potentially pathogenic Clostridium difficile contamination in household environs. Anaerobe 2014; 27:31.
  11. Kim KH, Fekety R, Batts DH, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis 1981; 143:42.
  12. Lefebvre SL, Weese JS. Contamination of pet therapy dogs with MRSA and Clostridium difficile. J Hosp Infect 2009; 72:268.
  13. Voth DE, Ballard JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005; 18:247.
  14. Lima AA, Innes DJ Jr, Chadee K, et al. Clostridium difficile toxin A. Interactions with mucus and early sequential histopathologic effects in rabbit small intestine. Lab Invest 1989; 61:419.
  15. Riegler M, Sedivy R, Pothoulakis C, et al. Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 1995; 95:2004.
  16. Lyras D, O'Connor JR, Howarth PM, et al. Toxin B is essential for virulence of Clostridium difficile. Nature 2009; 458:1176.
  17. Alfa MJ, Kabani A, Lyerly D, et al. Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile-associated diarrhea. J Clin Microbiol 2000; 38:2706.
  18. Drudy D, Fanning S, Kyne L. Toxin A-negative, toxin B-positive Clostridium difficile. Int J Infect Dis 2007; 11:5.
  19. 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.
  20. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353:2433.
  21. 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.
  22. Petrella LA, Sambol SP, Cheknis A, et al. Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain. Clin Infect Dis 2012; 55:351.
  23. Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med 2015; 372:1539.
  24. Leung DY, Kelly CP, Boguniewicz M, et al. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991; 118:633.
  25. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000; 342:390.
  26. Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 2015; 313:1719.
  27. Shim JK, Johnson S, Samore MH, et al. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998; 351:633.
  28. Jiang ZD, Garey KW, Price M, et al. Association of interleukin-8 polymorphism and immunoglobulin G anti-toxin A in patients with Clostridium difficile-associated diarrhea. Clin Gastroenterol Hepatol 2007; 5:964.
  29. Eglow R, Pothoulakis C, Itzkowitz S, et al. Diminished Clostridium difficile toxin A sensitivity in newborn rabbit ileum is associated with decreased toxin A receptor. J Clin Invest 1992; 90:822.
  30. Keel MK, Songer JG. The distribution and density of Clostridium difficile toxin receptors on the intestinal mucosa of neonatal pigs. Vet Pathol 2007; 44:814.
  31. Lucado J, Gould C, Elixhauser A. Clostridium difficile Infections (CDI) in Hospital Stays, 2009. HCUP Statistical Brief #124. January 2012. Agency for Healthcare Research and Quality, Rockville, MD. Available at: www.hcup-us.ahrq.gov/reports/statbriefs/sb124.pdf (Accessed on August 10, 2015).
  32. Faden HS, Ma CX. The Diagnosis of Clostridium difficile Infection in Outpatient Pediatrics. Clin Pediatr (Phila) 2016; 55:871.
  33. 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.
  34. Centers for Disease Control and Prevention (CDC). Surveillance for community-associated Clostridium difficile--Connecticut, 2006. MMWR Morb Mortal Wkly Rep 2008; 57:340.
  35. Benson L, Song X, Campos J, Singh N. Changing epidemiology of Clostridium difficile-associated disease in children. Infect Control Hosp Epidemiol 2007; 28:1233.
  36. McDonald LC, Coignard B, Dubberke E, et al. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007; 28:140.
  37. Wendt JM, Cohen JA, Mu Y, et al. Clostridium difficile infection among children across diverse US geographic locations. Pediatrics 2014; 133:651.
  38. Tschudin-Sutter S, Tamma PD, Naegeli AN, et al. Distinguishing community-associated from hospital-associated Clostridium difficile infections in children: implications for public health surveillance. Clin Infect Dis 2013; 57:1665.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. Rousseau C, Lemée L, Le Monnier A, et al. Prevalence and diversity of Clostridium difficile strains in infants. J Med Microbiol 2011; 60:1112.
  44. Larson HE, Barclay FE, Honour P, Hill ID. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982; 146:727.
  45. Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981; 81:5.
  46. Al-Jumaili IJ, Shibley M, Lishman AH, Record CO. Incidence and origin of Clostridium difficile in neonates. J Clin Microbiol 1984; 19:77.
  47. Martirosian G, Kuipers S, Verbrugh H, et al. PCR ribotyping and arbitrarily primed PCR for typing strains of Clostridium difficile from a Polish maternity hospital. J Clin Microbiol 1995; 33:2016.
  48. Rousseau C, Poilane I, De Pontual L, et al. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis 2012; 55:1209.
  49. Adlerberth I, Huang H, Lindberg E, et al. Toxin-producing Clostridium difficile strains as long-term gut colonizers in healthy infants. J Clin Microbiol 2014; 52:173.
  50. Holst E, Helin I, Mårdh PA. Recovery of Clostridium difficile from children. Scand J Infect Dis 1981; 13:41.
  51. Jangi S, Lamont JT. Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. J Pediatr Gastroenterol Nutr 2010; 51:2.
  52. Cooperstock M, Riegle L, Woodruff CW, Onderdonk A. Influence of age, sex, and diet on asymptomatic colonization of infants with Clostridium difficile. J Clin Microbiol 1983; 17:830.
  53. Stark PL, Lee A, Parsonage BD. Colonization of the large bowel by Clostridium difficile in healthy infants: quantitative study. Infect Immun 1982; 35:895.
  54. Stoesser N, Crook DW, Fung R, et al. Molecular epidemiology of Clostridium difficile strains in children compared with that of strains circulating in adults with Clostridium difficile-associated infection. J Clin Microbiol 2011; 49:3994.
  55. Wilcox MH, Mooney L, Bendall R, et al. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 2008; 62:388.
  56. Leibowitz J, Soma VL, Rosen L, et al. Similar proportions of stool specimens from hospitalized children with and without diarrhea test positive for Clostridium difficile. Pediatr Infect Dis J 2015; 34:261.
  57. Burgner D, Siarakas S, Eagles G, et al. A prospective study of Clostridium difficile infection and colonization in pediatric oncology patients. Pediatr Infect Dis J 1997; 16:1131.
  58. Hourigan SK, Chirumamilla SR, Ross T, et al. Clostridium difficile carriage and serum antitoxin responses in children with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19:2744.
  59. 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.
  60. Clabots CR, Johnson S, Olson MM, et al. Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis 1992; 166:561.
  61. Samore MH, Venkataraman L, DeGirolami PC, et al. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996; 100:32.
  62. Shaughnessy MK, Micielli RL, DePestel DD, et al. Evaluation of hospital room assignment and acquisition of Clostridium difficile infection. Infect Control Hosp Epidemiol 2011; 32:201.
  63. Centers for Disease Control and Prevention (CDC). Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005. MMWR Morb Mortal Wkly Rep 2005; 54:1201.
  64. Toltzis P, Kim J, Dul M, et al. Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children. J Pediatr 2009; 154:607.
  65. 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.
  66. Deshpande A, Pasupuleti V, Thota P, et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J Antimicrob Chemother 2013; 68:1951.
  67. Sandora TJ, Fung M, Flaherty K, et al. Epidemiology and risk factors for Clostridium difficile infection in children. Pediatr Infect Dis J 2011; 30:580.
  68. Tamma PD, Sandora TJ. Clostridium difficile Infection in Children: Current State and Unanswered Questions. J Pediatric Infect Dis Soc 2012; 1:230.
  69. Owens RC Jr, Donskey CJ, Gaynes RP, et al. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 2008; 46 Suppl 1:S19.
  70. 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.
  71. Turco R, Martinelli M, Miele E, et al. Proton pump inhibitors as a risk factor for paediatric Clostridium difficile infection. Aliment Pharmacol Ther 2010; 31:754.
  72. Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol 2012; 107:1001.
  73. Nylund CM, Eide M, Gorman GH. Association of Clostridium difficile infections with acid suppression medications in children. J Pediatr 2014; 165:979.
  74. Freedberg DE, Lamousé-Smith ES, Lightdale JR, et al. Use of Acid Suppression Medication is Associated With Risk for C. difficile Infection in Infants and Children: A Population-based Study. Clin Infect Dis 2015; 61:912.
  75. Chen KT, Stephens DJ, Anderson E, et al. Clostridium difficile infection in the pediatric surgery population. J Pediatr Surg 2012; 47:1385.
  76. Castagnola E, Battaglia T, Bandettini R, et al. Clostridium difficile-associated disease in children with solid tumors. Support Care Cancer 2009; 17:321.
  77. Tai E, Richardson LC, Townsend J, et al. Clostridium difficile infection among children with cancer. Pediatr Infect Dis J 2011; 30:610.
  78. Perlmutter DH, Leichtner AM, Goldman H, Winter HS. Chronic diarrhea associated with hypogammaglobulinemia and enteropathy in infants and children. Dig Dis Sci 1985; 30:1149.
  79. de Blank P, Zaoutis T, Fisher B, et al. Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer. J Pediatr 2013; 163:699.
  80. Pascarella F, Martinelli M, Miele E, et al. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr 2009; 154:854.
  81. Sandberg KC, Davis MM, Gebremariam A, Adler J. Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011. J Pediatr Gastroenterol Nutr 2015; 60:486.
  82. Martinelli M, Strisciuglio C, Veres G, et al. Clostridium difficile and pediatric inflammatory bowel disease: a prospective, comparative, multicenter, ESPGHAN study. Inflamm Bowel Dis 2014; 20:2219.
  83. Yahav J, Samra Z, Blau H, et al. Helicobacter pylori and Clostridium difficile in cystic fibrosis patients. Dig Dis Sci 2006; 51:2274.
  84. Rivlin J, Lerner A, Augarten A, et al. Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis. J Pediatr 1998; 132:177.
  85. Hussain SZ, Chu C, Greenberg DP, et al. Clostridium difficile colitis in children with cystic fibrosis. Dig Dis Sci 2004; 49:116.
  86. Yates B, Murphy DM, Fisher AJ, et al. Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation. Thorax 2007; 62:554.
  87. Theunissen C, Knoop C, Nonhoff C, et al. Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation. Transpl Infect Dis 2008; 10:240.
  88. Urushihara N, Kohno S, Hasegawa S. Pseudomembranous enterocolitis and hemorrhagic necrotizing enterocolitis in Hirschsprung's disease. Surg Today 1994; 24:221.
  89. Mc Laughlin D, Friedmacher F, Puri P. The impact of Clostridium difficile on paediatric surgical practice: a systematic review. Pediatr Surg Int 2014; 30:853.
  90. Williams RN, Hemingway D, Miller AS. Enteral Clostridium difficile, an emerging cause for high-output ileostomy. J Clin Pathol 2009; 62:951.
  91. Causey MW, Spencer MP, Steele SR. Clostridium difficile enteritis after colectomy. Am Surg 2009; 75:1203.
  92. Narchi H, Beattie TJ, Taylor RG, et al. Pseudomembranous colitis in association with Henoch Schonlein purpura. Scott Med J 1988; 33:308.
  93. Boey CC, Ramanujam TM, Looi LM. Clostridium difficile-related necrotizing pseudomembranous enteritis in association with Henoch-Schonlein purpura. J Pediatr Gastroenterol Nutr 1997; 24:426.
  94. Rooney N, Variend S, Taitz LS. Haemolytic uraemic syndrome and pseudomembranous colitis. Pediatr Nephrol 1988; 2:415.
  95. Burgner DP, Rfidah H, Beattie TJ, Seal DV. Clostridium difficile after haemolytic uraemic syndrome. Arch Dis Child 1993; 69:239.
  96. Butani L. Hemolytic uremic syndrome associated with Clostridium difficile colitis. Pediatr Nephrol 2004; 19:1430.
  97. Thompson CM Jr, Gilligan PH, Fisher MC, Long SS. Clostridium difficile cytotoxin in a pediatric population. Am J Dis Child 1983; 137:271.
  98. Schechter R, Peterson B, McGee J, et al. Clostridium difficile colitis associated with infant botulism: near-fatal case analogous to Hirschsprung's enterocolitis. Clin Infect Dis 1999; 29:367.