Skip to main content Accessibility help

Oral vancomycin prophylaxis during systemic antibiotic exposure to prevent Clostridiodes difficile infection relapses

  • Daniel A. Caroff (a1) (a2), John T. Menchaca (a3), Zilu Zhang (a1), Chanu Rhee (a1) (a4), Michael S. Calderwood (a5), David W. Kubiak (a6), Deborah S. Yokoe (a7) and Michael Klompas (a1) (a4)...



To determine whether oral vancomycin prophylaxis accompanying systemic antibiotics reduces the risk of relapse in patients with history of Clostridioides difficile infection (CDI).


Retrospective cohort study.


Adult inpatients with a history of CDI who received systemic antibiotics in either of 2 hospitals between January 2009 and June 2015.


We compared relapse rates in patients who started oral vancomycin concurrently with systemic antibiotics (exposed group) versus those who did not. We assessed for CDI relapse by toxin or nucleic acid testing at 90 days. We used inverse probability weighting and machine learning to adjust for confounders, to estimate propensity for treatment, and to calculate odds ratios for CDI relapse. We performed secondary analyses limited to toxin-positive relapses, patients with 1 versus >1 prior CDI episodes, and patients who received oral vancomycin on each antibiotic day.


CDI relapse occurred within 90 days in 19 of 193 exposed patients (9.8%) versus 53 of 567 unexposed patients (9.4%; unadjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.60–1.81; adjusted OR, 0.63; 95% CI, 0.35–1.14). CDI relapses at 90 days were less frequent in exposed patients with only 1 prior episode of CDI (OR, 0.42; 95% CI, 0.19–0.93) but not in those with >1 prior episode (OR, 1.19; 95% CI, 0.42–3.33). Our findings were consistent with a lack of benefit of oral vancomycin when restricting results to toxin-positive relapses and to patients who received vancomycin each antibiotic day.


Prophylactic oral vancomycin was not consistently associated with reduced risk of CDI relapse among hospitalized patients receiving systemic antibiotics. However, patients with only 1 prior CDI episode may benefit.


Corresponding author

Author for correspondence: Daniel A. Caroff, E-mail:; Michael Klompas, E-mail:


Hide All
1. Magill, SS, Edwards, JR, Bamberg, W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:11981208.
2. Lessa, FC, Mu, Y, Bamberg, WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825834.
3. Cornely, OA, Crook, DW, Esposito, R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis 2012;12:281289.
4. Louie, TJ, Miller, MA, Mullane, KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364:422431.
5. Rodrigues, R, Barber, GE, Ananthakrishnan, AN. A Comprehensive study of costs associated with recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol 2017;38:196202.
6. Van Hise, NW, Bryant, AM, Hennessey, EK, Crannage, AJ, Khoury, JA, Manian, FA. Efficacy of oral vancomycin in preventing recurrent Clostridium difficile infection in patients treated with systemic antimicrobial agents. Clin Infect Dis 2016;63:651653.
7. Carignan, A, Poulin, S, Martin, P, et al. Efficacy of secondary prophylaxis with vancomycin for preventing recurrent Clostridium difficile infections. Am J Gastroenterol 2016;111:18341840.
8. Stevens, V, Dumyati, G, Fine, LS, Fisher, SG, van Wijngaarden, E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011;53:4248.
9. Nelson, DE, Auerbach, SB, Baltch, AL, et al. Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins. Infect Control Hosp Epidemiol 1994;15:8894.
10. Bignardi, GE. Risk factors for Clostridium difficile infection. J Hosp Infect 1998;40:115.
11. McFarland, LV, Surawicz, CM, Stamm, WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J Infect Dis 1990;162:678684.
12. Zacharioudakis, IM, Zervou, FN, Pliakos, EE, Ziakas, PD, Mylonakis, E. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol 2015;110:381390.
13. 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.
14. Elixhauser, A, Steiner, C, Harris, DR, Coffey, RM. Comorbidity measures for use with administrative data. Med Care 1998;36:827.
15. Brown, KA, Khanafer, N, Daneman, N, Fisman, DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013;57:23262332.
16. Pirracchio, R, Petersen, ML, van der Laan, M. Improving propensity score estimators’ robustness to model misspecification using super learner. Am J Epidemiol 2015;181:108119.
17. Gruber, S, van der Laan, M. tmle: an R package for targeted maximum likelihood estimation. J Stat Softw 2012;51:35.
18. Lee, BK, Lessler, J, Stuart, EA. Improving propensity score weighting using machine learning. Stat Med 2010;29:337346.
19. Johnson, S, Homann, SR, Bettin, KM, et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med 1992;117:297302.
20. Polage, CR, Gyorke, CE, Kennedy, MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015;175:17921801.
Type Description Title
Supplementary materials

Caroff et al. supplementary material
Appendix 1

 Word (66 KB)
66 KB


Altmetric attention score

Full text views

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

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed