Antibiotics & C-diff Risk

23 Feb

During one of our interventions we suggested modifying an antibiotic regimen to use, in our opinion, a less C-diffogenic antibiotic.  This prompted us to do a literature search on the C-diffogenicity (not sure if this is a word) of various antibiotics.

Several risk factors have been identified for Clostridium difficile infection (CDI).  Culprits include, increased age, use of acid suppression therapy, and antibiotic therapy to name a few (1).   The most widely reported and well documented risk factor is antimicrobial exposure (2).  Prudent antibiotic use and antimicrobial stewardship programs have been shown to decrease nosocomial CDI (3).  That being said, we have also encountered community acquired CDI in patients without prior antibiotic exposure (4).   

The postulated pathophysiology of antibiotic associated CDI is that antibiotic exposure/use disrupts the natural microflora of the colon (killing the good and bad bugs).  This microflora provides a defence against potential pathogens (e.g.  C. difficile) by inhibiting colonization.  Once this intestinal flora is altered it may take weeks for it to return to normal levels.  (5,6).   This concept of reverting back to the normal flora has been recently challenged in an editorial published in Nature.  The author suggests that sometimes the natural flora may never fully recover.  A very interesting read (10).  This disruption is thought to either cause an overgrowth of indigenous C. difficile or allow for ingested C. difficile spores to colonize the flora (7, 8, 9).

Back to the topic of this post.  I was unable to find a nice chart outlining the C-diffogenciity of various antibiotics.  We compiled this list based on the risk ratios of different antibiotics based on two published papers and our own clinical experience (1, 11).  Unfortunately there are no published prospective randomized trials that explore this issue (that I’m aware of).  Thus, this chart is likely affected by many biases and is our opinion.  Due to the complexity of CDI and lack of prospective clinical trials it’s difficult to say that a patient will acquire CDI by using a certain antibiotic.  If we aim to treat patients with the optimal antibiotic at the shortest duration we can minimize the collateral damage associated with antibiotic use (12).

Again, this chart is for informational purposes.  Any antibiotic exposure increases the risk of CDI.

Most likely to cause C diff Less likely to cause C. diff
Quinolones (moxifloxacin, levofloxacin, ciprofloxacin) Trimethoprim/sulfamethoxazole
Cephalosporins (1st generation may have lower risk) Nitrofurantoin
Clindamycin Macrolides (e.g. azithromycin, erythromycin)
Amoxicillin/Clavulanate Penicillin + Antistaphylococcal penicillins
  Aminoglycosides (e.g. tobramycin, gentamicin)
  Tetracyclines (large confidence interval)



  1.  Dial, S., Kezouh, A., Dascal, A., Barkun, A., & Suissa, S. (2008). Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection. CMAJ Canadian Medical Association Journal, 179(8), 767-772. Canadian Medical Association. Retrieved from
  2. Owens, R. C., Donskey, C. J., Gaynes, R. P., Loo, V. G., & Muto, C. A. (2008). Antimicrobial-associated risk factors for Clostridium difficile infection. (C J Donskey, R P Gaynes, V G Loo, & C A Muto, Eds.)Clinical Infectious Diseases, 46 Suppl 1(Suppl 1), S19-S31. Retrieved from
  3. Valiquette, L., Cossette, B., Garant, M.-P., Diab, H., & Pépin, J. (2007). Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clinical Infectious Diseases, 45 Suppl 2(Suppl 2), S112-S121. Retrieved from
  4. Kuntz, J. L., Chrischilles, E. A., Pendergast, J. F., Herwaldt, L. A., & Polgreen, P. M. (2011). Incidence of and risk factors for community-associated Clostridium difficile infection: A nested case-control study. The Journal of antimicrobial chemotherapy, 11(3), 194. BioMed Central. Retrieved from
  5. Donskey, C. J. (2004). The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clinical Infectious Diseases, 39(2), 219-226. Retrieved from
  6. Gerding, D. N. (2004). Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile-associated diarrhea: this is an antimicrobial resistance problem. Clinical Infectious Diseases. Retrieved from
  7. Wilson, K. H. (1993). The microecology of Clostridium difficile. Clinical Infectious Diseases, 16 Suppl 4(4), S214-S218. Retrieved from
  8. Chang, J. Y., Antonopoulos, D. A., Kalra, A., Tonelli, A., Khalife, W. T., Schmidt, T. M., & Young, V. B. (2008). Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. The Journal of Infectious Diseases, 197(3), 435-438. Oxford University Press. Retrieved from
  9. Rodriguez-Palacios, A., Staempfli, H. R., Duffield, T., & Weese, J. S. (2007). Clostridium difficile in Retail Ground Meat, Canada. Emerging Infectious Diseases, 13(3), 485-487. Centers for Disease Control and Prevention. Retrieved from
  10. Blaser, M. (2011). Antibiotic overuse: Stop the killing of beneficial bacteria. Nature, 476(7361), 393-394. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Retrieved from
  11. Bignardi, G. E. (1998). difficile Risk factors infection. The Journal of hospital infection, 40(1), 1-15. Elsevier. Retrieved from
  12. Stevens, V., Dumyati, G., Fine, L. S., Fisher, S. G., & Van Wijngaarden, E. (2011). Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clinical Infectious Diseases, 53(1), 42-48. Retrieved from

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