Skip to main content
    • Aa
    • Aa

Electronic Health Record–Based Detection of Risk Factors for Clostridium difficile Infection Relapse

  • Courtney Hebert (a1), Hongyan Du (a2), Lance R. Peterson (a3) and Ari Robicsek (a4) (a5)

A major challenge in treating Clostridium difficile infection (CDI) is relapse. Many new therapies are being developed to help prevent this outcome. We sought to establish risk factors for relapse and determine whether fields available in an electronic health record (EHR) could be used to identify high-risk patients for targeted relapse prevention strategies.


Retrospective cohort study.


Large clinical data warehouse at a 4-hospital healthcare organization.


Data were gathered from January 2006 through October 2010. Subjects were all inpatient episodes of a positive C. difficile test where patients were available for 56 days of follow-up.


Relapse was defined as another positive test between 15 and 56 days after the initial test. Multivariable regression was performed to identify factors independently associated with CDI relapse.


Eight hundred twenty-nine episodes met eligibility criteria, and 198 resulted in relapse (23.9%). In the final multivariable analysis, risk of relapse was associated with age (odds ratio [OR], 1.02 per year [95% confidence interval (CI), 1.01–1.03]), fluoroquinolone exposure in the 90 days before diagnosis (OR, 1.58 [95% CI, 1.11–2.26]), intensive care unit stay in the 30 days before diagnosis (OR, 0.47 [95% CI, 0.30–0.75]), cephalosporin (OR, 1.80 [95% CI, 1.19–2.71]), proton pump inhibitor (PPI; OR, 1.55 [95% CI, 1.05–2.29]), and metronidazole exposure after diagnosis (OR, 2.74 [95% CI, 1.64–4.60]). A prediction model tuned to ensure a 50% probability of relapse would flag 14.6% of CDI episodes.


Data from a comprehensive EHR can be used to identify patients at high risk for CDI relapse. Major risk factors include antibiotic and PPI exposure.

Corresponding author
Department of Bio-medical Informatics, Ohio State University Wexner Medical Center, 3190 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210 (
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1. MD Redelings , F Sorvillo , L Mascola . Increase in Clostridium difficile–related mortality rates, United States, 1999–2004. Emerg Infect Dis 2007;13(9):14171419.

2. CP Kelly , JT LaMont . Clostridium difficile: more difficult than ever. N Engl J Med 2008;359(18):19321940.

3. LC McDonald , M Owings , DB Jernigan . Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996–2003. Emerg Infect Dis 2006;12(3):409415.

4. LC McDonald , GE Killgore , A Thompson , et al.An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med 2005;353(23):24332441.

6. TJ Louie , MA Miller , KM Mullane , et al.Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364(5):422431.

7. I Lowy , DC Molrine , BA Leav , et al.Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010;362(3):197205.

9. A Linsky , K Gupta , EV Lawler , JR Fonda , JA Hermos . Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010;170(9):772778.

10. J Cadena , GR Thompson III JE Patterson , et al.Clinical predictors and risk factors for relapsing Clostridium difficile infection. Am J Med Sci 2010;339(4):350355.

11. J Pepin , ME Alary , L Valiquette , et al.Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005;40(11):15911597.

12. S Johnson , C Schriever , M Galang , CP Kelly , DN Gerding . Interruption of recurrent Clostridium difficile–associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007;44(6):846848.

13. LV McFarland , GW Elmer , CM Surawicz . Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 2002;97(7):17691775.

14. J O'Horo , N Safdar . The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review. Int J Infect Dis 2009;13(6):663667.

15. HK Choi , KH Kim , SH Lee , SJ Lee . Risk factors for recurrence of Clostridium difficile infection: effect of vancomycin-resistant enterococci colonization. J Korean Med Sci 2011;26(7):859864.

16. MY Hu , K Katchar , L Kyne , et al.Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 2009;136(4):12061214.

17. CE Metz , HB Kronman . Statistical significance tests for binormal ROC curves. J Math Psychol 1980;22(3):218243.

18. C Metz , P Wang , H Kronman . A new approach for testing the significance of differences between ROC curves from correlated data. In: F Deconinck , ed. Information Processing in Medical Imaging. The Hague: Nijhoff, 1984:432445.

20. RC Owens Jr CJ Donskey , RP Gaynes , VG Loo , CA Muto . Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 2008;46(suppl):S19S31.

21. MD Howell , V Novack , P Grgurich , et al.Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med 2010;170(9):784790.

22. S Dial , K Alrasadi , C Manoukian , A Huang , D Menzies . Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 2004;171(1):3338.

23. I Vesteinsdottir , S Gudlaugsdottir , R Einarsdottir , E Kalaitzakis , O Sigurdardottir , ES Bjornsson . Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study. Eur J Clin Microbiol Infect Dis 2012;31:26012610.

24. CS Kwok , AK Arthur , CI Anibueze , S Singh , R Cavallazzi , YK Loke . Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 2012;107:10111019.

25. A Deshpande , C Pant , V Pasupuleti , et al.Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastroenterol Hepatol 2012;10(3):225233.

26. BM Kuehn . Reflux drugs linked to C. difficile–related diarrhea. JAMA 2012;307(10):1014.

27. YG Kim , DY Graham , BI Jang . Proton pump inhibitor use and recurrent Clostridium difficile–associated disease: a case-control analysis matched by propensity score. J Clin Gastroenterol 2012;46(5):397400.

28. JW Kim , KL Lee , JB Jeong , et al.Proton pump inhibitors as a risk factor for recurrence of Clostridium difficile–associated diarrhea. World J Gastroenterol 2010;16(28):35733577.

29. RM Cadle , MD Mansouri , N Logan , DR Kudva , DM Musher . Association of proton-pump inhibitors with outcomes in Clostridium difficile colitis. Am J Health Syst Pharm 2007;64(22):23592363.

31. FA Zar , SR Bakkanagari , KM Moorthi , MB Davis . A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile–associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45(3):302307.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 18 *
Loading metrics...

Abstract views

Total abstract views: 128 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 29th April 2017. This data will be updated every 24 hours.