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Impact of Toxigenic Clostridium difficile Colonization on the Risk of Subsequent C. difficile Infection in Intensive Care Unit Patients

  • Sarah Tschudin-Sutter (a1) (a2) (a3), Karen C. Carroll (a4), Pranita D. Tamma (a5), Madeleine L. Sudekum (a1), Reno Frei (a6), Andreas F. Widmer (a2), Brandon C. Ellis (a4), John Bartlett (a1) and Trish M. Perl (a1) (a3)...



Clostridium difficile infection (CDI) in hospitalized patients is generally attributed to the current stay, but recent studies reveal high C. difficile colonization rates on admission.


To determine the rate of colonization with toxigenic C. difficile among intensive care unit patients upon admission as well as acquired during hospitalization, and the risk of subsequent CDI.


Prospective cohort study from April 15 through July 8, 2013. Adults admitted to an intensive care unit within 48 hours of admission to the Johns Hopkins Hospital, Baltimore, Maryland, were screened for colonization with toxigenic C. difficile. The primary outcome was risk of developing CDI.


Among 542 patients, 17 (3.1%) were colonized with toxigenic C. difficile on admission and an additional 3 patients were found to be colonized during hospitalization. Both colonization with toxigenic C. difficile on admission and colonization during hospitalization were associated with an increased risk for development of CDI (relative risk, 10.29 [95% CI, 2.24–47.40], P=.003; and 15.66 [4.01–61.08], P<.001, respectively). Using multivariable analysis, colonization on admission and colonization during hospitalization were independent predictors of CDI (relative risk, 8.62 [95% CI, 1.48–50.25], P=.017; and 10.93 [1.49–80.20], P=.019, respectively), while adjusting for potential confounders.


In intensive care unit patients, colonization with toxigenic C. difficile is an independent risk factor for development of subsequent CDI. Further studies are needed to identify populations with higher toxigenic C. difficile colonization rates possibly benefiting from screening or avoidance of agents known to promote CDI.

Infect. Control Hosp. Epidemiol. 2015;36(11):1324–1329


Corresponding author

Address correspondence to Sarah Tschudin-Sutter, MD, MSc, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland (


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Presented in part: 24th European Congress of Clinical Microbiology and Infectious Diseases; Barcelona, Spain; May 11, 2014 (Abstract P0773).



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1. Kyne, L, Hamel, MB, Polavaram, R, Kelly, CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile . Clin Infect Dis 2002;34:346353.
2. Magill, SS, Edwards, JR, Bamberg, W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:11981208.
3. Micek, ST, Schramm, G, Morrow, L, et al. Clostridium difficile infection: a multicenter study of epidemiology and outcomes in mechanically ventilated patients. Crit Care Med 2013;41:19681975.
4. McDonald, LC. Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012;61:157162.
5. 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;31:431455.
6. Deutsches Institut für Normung EN. Chemische Desinfektionsmittel und Antiseptika. Hygienische Händedesinfektion. Prüfverfahren und Anforderungen (Phase 2/Stufe 2). 1997.
7. Stubbs, SL, Brazier, JS, O'Neill, GL, Duerden, BI. PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium difficile and construction of a library consisting of 116 different PCR ribotypes. J Clin Microbiol 1999;37:461463.
8. Zou, G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004;159:702706.
9. Hung, YP, Tsai, PJ, Hung, KH, et al. Impact of toxigenic Clostridium difficile colonization and infection among hospitalized adults at a district hospital in southern Taiwan. PLoS One 2012;7:e42415.
10. Alasmari, F, Seiler, SM, Hink, T, Burnham, CA, Dubberke, ER. Prevalence and risk factors for asymptomatic Clostridium difficile carriage. Clin Infect Dis 2014;59:216222.
11. Loo, VG, Bourgault, AM, Poirier, L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011;365:16931703.
12. Curry, SR, Schlackman, JL, Hamilton, TM, et al. Perirectal swab surveillance for Clostridium difficile by use of selective broth preamplification and real-time PCR detection of tcdB. J Clin Microbiol 2011;49:37883793.
13. McFarland, LV, Mulligan, ME, Kwok, RY, Stamm, WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204210.
14. Brazier, JS, Fitzgerald, TC, Hosein, I, et al. Screening for carriage and nosocomial acquisition of Clostridium difficile by culture: a study of 284 admissions of elderly patients to six general hospitals in Wales. J Hosp Infect 1999;43:317319.
15. Hutin, Y, Casin, I, Lesprit, P, et al. Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward. Clin Infect Dis 1997;24:920924.
16. 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;342:390397.
17. Leekha, S, Aronhalt, KC, Sloan, LM, Patel, R, Orenstein, R. Asymptomatic Clostridium difficile colonization in a tertiary care hospital: admission prevalence and risk factors. Am J Infect Control 2013;41:390393.
18. Samore, MH, DeGirolami, PC, Tlucko, A, Lichtenberg, DA, Melvin, ZA, Karchmer, AW. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181187.
19. Marciniak, C, Chen, D, Stein, AC, Semik, PE. Prevalence of Clostridium difficile colonization at admission to rehabilitation. Arch Phys Med Rehabil 2006;87:10861090.
20. Khanna, S, Pardi, DS, Aronson, SL, et al. The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am J Gastroenterol 2012;107:8995.
21. Severe Clostridium difficile–associated disease in populations previously at low risk—four states, 2005. MMWR Morb Mortal Wkly Rep 2005;54:12011205.
22. Surveillance for community-associated Clostridium difficile—Connecticut, 2006. MMWR Morb Mortal Wkly Rep 2008;57:340343.
23. Garey, KW, Jiang, ZD, Yadav, Y, Mullins, B, Wong, K, Dupont, HL. Peripartum Clostridium difficile infection: case series and review of the literature. Am J Obstet Gynecol 2008;199:332337.
24. Rouphael, NG, O'Donnell, JA, Bhatnagar, J, et al. Clostridium difficile–associated diarrhea: an emerging threat to pregnant women. Am J Obstet Gynecol 2008;198:635.e1–636.
25. Benson, L, Song, X, Campos, J, Singh, N. Changing epidemiology of Clostridium difficile–associated disease in children. Infect Control Hosp Epidemiol 2007;28:12331235.
26. Hoover, DG, Rodriguez-Palacios, A. Transmission of Clostridium difficile in foods. Infect Dis Clin North Am 2013;27:675685.
27. Deshpande, A, Pant, C, Pasupuleti, V, et al. Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastroenterol Hepatol 2012;10:225233.
28. Dubberke, ER, Reske, KA, Olsen, MA, et al. Evaluation of Clostridium difficile–associated disease pressure as a risk factor for C. difficile–associated disease. Arch Intern Med 2007;167:10921097.
29. Shim, JK, Johnson, S, Samore, MH, Bliss, DZ, Gerding, DN. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998;351:633636.
30. Kyne, L, Warny, M, Qamar, A, Kelly, CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 2001;357:189193.
31. Lowy, I, Molrine, DC, Leav, BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010;362:197205.


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