Skip to main content


Log in

Diagnostic Modality of Clostridioides difficile Infection Predicts Treatment Response and Outcomes in Inflammatory Bowel Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript



Inflammatory bowel disease (IBD) patients are at increased risk of developing Clostridioides difficile infection (CDI). Common methods to diagnose CDI involve a combination of tests including the toxin A/B enzyme immunoassay (Toxin) and toxin gene polymerase chain reaction assay (PCR). Disease outcomes in Toxin+ versus Toxin-PCR+ IBD patients remain unclear.


This study aimed to examine the response to antibiotics and risk of IBD therapy escalation in Toxin+ versus Toxin-PCR+ patients.


IBD patients at an academic center with CDI diagnosis based on Toxin+ or Toxin-PCR+ from 2012 to 2017 were identified. Comparisons of response to antibiotics within 30 days and escalation of IBD therapy within 90 days of CDI diagnosis between these two groups were analyzed by Chi-square analysis. Multivariable regression analysis examined factors associated with antibiotic response.


Among 92 patients included, 61% had Crohn’s disease and 39% had ulcerative colitis. 70% tested Toxin-PCR+. 60% received vancomycin or fidaxomicin to treat CDI. 82% of Toxin+ patients responded to antibiotics compared to 25% of Toxin-PCR+ patients (p < 0.001). 21% of Toxin+ patients required IBD therapy escalation compared to 63% of Toxin-PCR+ patients (p < 0.001). When adjusted for the types of antibiotics used, IBD subtypes, and immunosuppression status, positivity to Toxin (OR 14.85, CI 4.62–47.72) was the most significant predictor of response to antibiotics.


Toxin+ compared to Toxin-PCR+ IBD patients had a significantly higher rate of response to antibiotics and lower chances of requiring IBD therapy escalation. Future outcome studies involving CDI in IBD patients should be stratified by modality of diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others


  1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825–834.

    Article  CAS  Google Scholar 

  2. Khanna S, Shin A, Kelly CP. Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017;15:166–174.

    Article  Google Scholar 

  3. Clayton EM, Rea MC, Shanahan F, et al. The vexed relationship between Clostridium difficile and inflammatory bowel disease: an assessment of carriage in an outpatient setting among patients in remission. Am J Gastroenterol. 2009;104:1162–1169.

    Article  Google Scholar 

  4. Rao K, Higgins PDR. Epidemiology, diagnosis, and management of Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1744–1754.

    Article  Google Scholar 

  5. Tang YM, Stone CD. Clostridium difficile infection in inflammatory bowel disease: challenges in diagnosis and treatment. Clin J Gastroenterol. 2017;10:112–123.

    Article  Google Scholar 

  6. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478–498.

    Article  CAS  Google Scholar 

  7. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:987–994.

    Article  CAS  Google Scholar 

  8. Burnham C-AD, Carroll KC. Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories. Clin Microbiol Rev. 2013;26:604–630.

    Article  CAS  Google Scholar 

  9. Longtin Y, Trottier S, Brochu G, et al. Impact of the type of diagnostic assay on Clostridium difficile infection and complication rates in a mandatory reporting program. Clin Infect Dis. 2013;56:67–73.

    Article  Google Scholar 

  10. Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792–1801.

    Article  Google Scholar 

  11. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19 Suppl A:5A–36A.

    Article  Google Scholar 

  12. Kyne L, Warny M, Qamar A, et al. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357:189–193.

    Article  CAS  Google Scholar 

  13. Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197:435–438.

    Article  Google Scholar 

  14. Ott SJ, Musfeldt M, Wenderoth DF, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut. 2004;53:685–693.

    Article  CAS  Google Scholar 

  15. D’Aoust J, Battat R, Bessissow T. Management of inflammatory bowel disease with Clostridium difficile infection. World J Gastroenterol. 2017;23:4986–5003.

    Article  Google Scholar 

  16. Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: Management of Crohn’s Disease in Adults. Am J Gastroenterol. 2018;113:481–517.

    Article  Google Scholar 

  17. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114:384–413.

    Article  Google Scholar 

  18. Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev. 2017;3:CD004610.

    PubMed  Google Scholar 

  19. Wang Y, Atreja A, Wu X, et al. Similar outcomes of IBD inpatients with Clostridium difficile infection detected by ELISA or PCR assay. Dig Dis Sci. 2013;58:2308–2313.

    Article  CAS  Google Scholar 

  20. Reinink AR, Limsrivilai J, Reutemann BA, et al. Differentiating Clostridium difficile Colitis from Clostridium difficile colonization in ulcerative colitis: a role for procalcitonin. Digestion. 2017;96:207–212.

    Article  CAS  Google Scholar 

  21. Desai M, Gray J, Nguyen VQ, et al. Differentiating C. difficile disease from colonization in patients with and without inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2020 (in press).

Download references


This study was not funded.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Vu Q. Nguyen.

Ethics declarations

Conflict of interest

Vu Q. Nguyen has received grant support from AbbVie Inc and American College of Gastroenterology. Dario Sorrentino has received consulting fees from Abbott/AbbVie, Centocor Inc., Ferring, Hoffman-LaRoche, Giuliani, Schering-Plough, MSD, Janssen Research & Development, and TechLab and research grants from AbbVie, Centocor, Crohn’s and Colitis Foundations, Janssen Research & Development, LLC, Medtronics, Schering-Plough, Takeda, TechLab, and serves in the Speakers Bureau of AbbVie and the National Faculty of Janssen.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, A., Wash, C., Wu, Y. et al. Diagnostic Modality of Clostridioides difficile Infection Predicts Treatment Response and Outcomes in Inflammatory Bowel Disease. Dig Dis Sci 66, 547–553 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: