Tools for Practice


#92 Probiotics C the Difference for the Prevention of C diff


CLINICAL QUESTION
Do probiotics prevent Clostridium difficile-associated diarrhea (CDAD) in patients taking antibiotics?

BOTTOM LINE
Probiotics may reduce the incidence of CDAD in patients on antibiotics, preventing one case of CDAD in 29 but no benefits are seen in studies not funded by manufacturers.  Furthermore, the ideal product, length of therapy, and safety of probiotics (particularly in the immunocompromised) is unknown.


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EVIDENCE
Cochrane review1 of 31 randomized controlled trials (RCTs) of 4492 mostly adult inpatients using a variety of probiotics for a variable length of time (majority for duration of antibiotic use or up to 14 days after antibiotics finished): 
  • Outcomes: 
    • Reduction in CDAD incidence:  
      • Probiotics 2.0%, placebo 5.5%, number needed to treat (NNT)=29 
  • Limitations: 
    • 13 trials missed up to 45% of CDAD data 
    • 8 trials did not report CDAD 
    • Most studies funded by probiotic manufacturer.
Similar results found in older systematic reviews.2-4  RCT5 of 2981 elderly inpatients given probiotic (containing L acidophilus and Bifidobacterium) or placebo for 21 days 
  • No difference in CDAD (probiotic 1.2%, placebo 0.8%), but event rate lower than in other studies 
  • Systematic review6 including this study found similar results to Cochrane review. 
With the above RCT5 the Cochrane meta-analysis1 was re-run examining the influence of funding,7 the relative risk (confidence intervals) of CDAD was 
  • 0.79 (0.41-1.53) in public funded, no effect. 
  • 0.34 (0.24-0.48) in industry funded, reduced CDAD with probiotics.
Context:  
  • Risk factors for CDAD:8-10 
    • Primarily: antibiotic use (especially cephalosporins, clindamycin and quinolones) and hospitalization 
    • Also: Advancing age, concurrent diseases (especially inflammatory bowel disease), use of corticosteroids, PPIs and H2RAs.
  • Probiotics also decrease antibiotic-associated diarrhea in adults and children (NNT=13).1 
  • Cases of fungemia and bacteremia reported in immunocompromised patients given probiotic,11 but overall adverse events seem similar to placebo.1,11  
  • American guidelines12 do not endorse probiotics for CDAD prevention, but they do not cite systematic reviews discussed here. 
  • The Canadian Pediatrics Society provide conflicting13,14 recommendations regarding probiotics for CDAD prevention. 
  • Approximate Canadian cost for 14 days of probiotics with evidence for CDAD prevention: 
    • Bio-K+ (L acidophilus, L casei):  $13 
    • TuZen (L plantarum 299v): $37 
    • Florastor (S boulardii):  $45 
    • VSL#3 (8 species): $112 
Ricky updated Aug 11 2016
June 24, 2013

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Author(s):

  • Daniel Rainkie BScPharm ACPR PharmD
  • Michael R Kolber MD CCFP MSc

1. Goldenberg JZ, Ma SSY, Saxton Martzen MR, et al. Cochrane Database Syst Rev 2013;5:CD006095.

2. Johnston BC, Ma SSY, Goldenberg JZ, et al. Ann Intern Med 2012;157:878-88.

3. Hempel S, Newberry SJ, Maher AR, et al. JAMA 2012;307:1959-69.

4. Avadhani A, Miley H. J Am Acad Nurse Prac 2011;23:269-74.

5. Allen SJ, Wareham K, Wang D, et al. Lancet 2013;382:1249-57.

6. Lau CSM, Chamberlain RS. Int J Gen Med 2016;9:27-37.

7. Kolber MR, Vandermeer B, Allan GM. Am J Gastroenterol. 2014;109:1081-2.

8. Brown KA, Khanafer N, Daneman N, et al. Antimicrob Agents Chemother 2013;57:2326-32.

9. Kwok CS, Arthur AK, Anibueze CI, et al. Am J Gastroenterol 2012;107:1011–9.

10. Furuya-Kanamori L, Stone JC, Clark J, et al. Infect Control Hosp Epidemiol 2015;36:132-41.

11. Hempel S, Newberry S, Ruelaz A, et al. Safety of Probiotics to Reduce Risk and Prevent or Treat Disease. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Apr. (Evidence Reports/Technology Assessments, No. 200.) Available from: http://www.ncbi.nlm.nih.gov/books/NBK56091/

12. Surawicz CM, Brandt LJ, Binion DG. Am J Gastroenterol 2013;108:478-98.

13. http://www.cps.ca/documents/position/clostridium-difficile-in-paediatric-populations [Accessed 11 Aug 2016]

14. http://www.cps.ca/documents/position/probiotics-in-the-paediatric-population [Accessed 11 Aug 2016]

Authors do not have any conflicts of interest to declare.