DOI QR코드

DOI QR Code

Clostridium difficile Infection at Diagnosis and during the Disease Course of Pediatric Inflammatory Bowel Disease

  • Kim, Do Hyun (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Cho, Jin Min (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Yang, Hye Ran (Department of Pediatrics, Seoul National University Bundang Hospital)
  • Received : 2017.10.09
  • Accepted : 2017.12.22
  • Published : 2018.01.15

Abstract

Purpose: Clostridium difficile colonization and infection are commonly associated with poor outcomes in patients with pediatric inflammatory bowel disease (PIBD). We aimed to investigate the prevalence of C. difficile colonization and infection at the time of diagnosis and to evaluate risk factors associated with the development of C. difficile infection during the course of PIBD treatment. Methods: We retrospectively enrolled a total of 59 children who were newly diagnosed with PIBD at the tertiary medical center. All patients underwent C. difficile toxin assays and cultures initially and at every follow-up during the disease course. Kaplan-Meier survival analysis and Cox regression test were used for statistical analysis. Results: Initial cultures for C. difficile were positive in 13 (22.0%) of 59 PIBD patients, whereas initial toxin assays were positive in 3 patients (5.1%). During treatment, C. difficile cultures converted to positive in 28 (47.5%) in addition to 13 patients who were initially culture-positive, and C. difficile toxins converted to positive in 13 (22.0%) in addition to 3 originally toxin-positive patients. Antibiotic usage alone was significantly associated with the development of C. difficile colonization (p=0.011), and the length of hospitalization was associated with the development of C. difficile infection (p=0.032). Conclusion: C. difficile colonization and infection occur frequently during the disease course of PIBD. Antibiotic usage and longer hospital stay were significant risks factors for the conversion of C. difficile status in PIBD patients undergoing treatment.

Keywords

References

  1. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994;330:257-62. https://doi.org/10.1056/NEJM199401273300406
  2. Pascarella F, Martinelli M, Miele E, Del Pezzo M, Roscetto E, Staiano A. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr 2009;154:854-8. https://doi.org/10.1016/j.jpeds.2008.12.039
  3. Sokol H, Lay C, Seksik P, Tannock GW. Analysis of bacterial bowel communities of IBD patients: what has it revealed? Inflamm Bowel Dis 2008;14:858-67. https://doi.org/10.1002/ibd.20392
  4. Ananthakrishnan AN, McGinley EL, Saeian K, Binion DG. Temporal trends in disease outcomes related to Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:976-83. https://doi.org/10.1002/ibd.21457
  5. Mezoff E, Mann EA, Hart KW, Lindsell CJ, Cohen MB. Clostridium difficile infection and treatment in the pediatric inflammatory bowel disease population. J Pediatr Gastroenterol Nutr 2011;52:437-41. https://doi.org/10.1097/MPG.0b013e3181f97209
  6. Wultanska D, Banaszkiewicz A, Radzikowski A, Obuch- Woszczatynski P, Mlynarczyk G, Brazier JS, et al. Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease. Eur J Clin Microbiol Infect Dis 2010;29:1265-70. https://doi.org/10.1007/s10096-010-0997-9
  7. Kelsen JR, Kim J, Latta D, Smathers S, McGowan KL, Zaoutis T, et al. Recurrence rate of Clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17:50-5. https://doi.org/10.1002/ibd.21421
  8. Pant C, Anderson MP, Deshpande A, Altaf MA, Grunow JE, Atreja A, et al. Health care burden of Clostridium difficile infection in hospitalized children with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19:1080-5. https://doi.org/10.1097/MIB.0b013e3182807563
  9. Banaszkiewicz A, Kowalska-Duplaga K, Pytrus T, Pituch H, Radzikowski A. Clostridium difficile infection in newly diagnosed pediatric patients with inflammatory bowel disease: prevalence and risk factors. Inflamm Bowel Dis 2012;18:844-8. https://doi.org/10.1002/ibd.21837
  10. Banaszkiewicz A, Pituch H. Clostridium difficile infection in children with inflammatory bowel disease: current evidence. Curr Pharm Des 2014;20:4549-55. https://doi.org/10.2174/13816128113196660729
  11. Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:345-51. https://doi.org/10.1016/j.cgh.2006.12.028
  12. Rodemann JF, Dubberke ER, Reske KA, Seo DH, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:339-44. https://doi.org/10.1016/j.cgh.2006.12.027
  13. 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. https://doi.org/10.1111/j.1572-0241.2007.01780.x
  14. Schutze GE, Willoughby RE; Committee on Infectious Diseases; American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics 2013;131:196-200. https://doi.org/10.1542/peds.2012-2992
  15. Ananthakrishnan AN, Issa M, Binion DG. Clostridium difficile and inflammatory bowel disease. Gastroenterol Clin North Am 2009;38:711-28. https://doi.org/10.1016/j.gtc.2009.07.003
  16. Musa S, Thomson S, Cowan M, Rahman T. Clostridium difficile infection and inflammatory bowel disease. Scand J Gastroenterol 2010;45:261-72. https://doi.org/10.3109/00365520903497098
  17. Goodhand JR, Alazawi W, Rampton DS. Systematic review: Clostridium difficile and inflammatory bowel disease. Aliment Pharmacol Ther 2011;33:428-41. https://doi.org/10.1111/j.1365-2036.2010.04548.x
  18. Gryboski JD. Clostridium difficile in inflammatory bowel disease relapse. J Pediatr Gastroenterol Nutr 1991;13:39-41. https://doi.org/10.1097/00005176-199107000-00007
  19. Markowitz JE, Brown KA, Mamula P, Drott HR, Piccoli DA, Baldassano RN. Failure of single-toxin assays to detect Clostridium difficile infection in pediatric inflammatory bowel disease. Am J Gastroenterol 2001; 96:2688-90. https://doi.org/10.1111/j.1572-0241.2001.04125.x
  20. Monaghan TM, Cockayne A, Mahida YR. Pathogenesis of Clostridium difficile infection and its potential role in inflammatory bowel disease. Inflamm Bowel Dis 2015;21:1957-66. https://doi.org/10.1097/MIB.0000000000000461
  21. Gomez S, Chaves F, Orellana MA. Clinical, epidemiological and microbiological characteristics of relapse and re-infection in Clostridium difficile infection. Anaerobe 2017;48:147-51. https://doi.org/10.1016/j.anaerobe.2017.08.012
  22. Ott C, Girlich C, Klebl F, Plentz A, Iesalnieks I, Scholmerich J, et al. Low risk of Clostridium difficile infections in hospitalized patients with inflammatory bowel disease in a German tertiary referral center. Digestion 2011;84:187-92. https://doi.org/10.1159/000324617
  23. Sokol H, Lalande V, Landman C, Bourrier A, Nion-Larmurier I, Rajca S, et al. Clostridium difficile infection in acute flares of inflammatory bowel disease: a prospective study. Dig Liver Dis 2017;49:643-6. https://doi.org/10.1016/j.dld.2017.01.162
  24. Erb S, Frei R, Stranden AM, Dangel M, Tschudin-Sutter S, Widmer AF. Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients. Clin Microbiol Infect 2015;21:998.e9-15. https://doi.org/10.1016/j.cmi.2015.07.016
  25. Martinelli M, Strisciuglio C, Veres G, Paerregaard A, Pavic AM, Aloi M, et al. Clostridium difficile and pediatric inflammatory bowel disease: a prospective, comparative, multicenter, ESPGHAN study. Inflamm Bowel Dis 2014;20:2219-25. https://doi.org/10.1097/MIB.0000000000000219
  26. Saffouri G, Gupta A, Loftus EV Jr, Baddour LM, Pardi DS, Khanna S. The incidence and outcomes from Clostridium difficile infection in hospitalized adults with inflammatory bowel disease. Scand J Gastroenterol 2017;52:1240-7.
  27. Hojsak I, Ferenc T, Bojanic K, Misak Z, Mocic Pavic A, et al. Incidence of Clostridium difficile infection in children with inflammatory bowel disease compared to oncology and immunocompetent patients. Digestion 2012; 86:6-11.
  28. Peterson LR, Manson RU, Paule SM, Hacek DM, Robicsek A, Thomson RB Jr, et al. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007;45:1152-60. https://doi.org/10.1086/522185

Cited by

  1. Molecular characteristics of Clostridium difficile in children with acute gastroenteritis from Zhejiang vol.20, pp.None, 2018, https://doi.org/10.1186/s12879-020-05030-6