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Effectiveness of Probiotic for Primary Prevention of Clostridium difficile Infection: A Single-Center Before-and-After Quality Improvement Intervention at a Tertiary-Care Medical Center

  • William E. Trick (a1), Stephen J. Sokalski (a2), Stuart Johnson (a3), Kristen L. Bunnell (a4), Joseph Levato (a2), Michael J. Ray (a1) and Robert A. Weinstein (a1)...



To evaluate probiotics for the primary prevention of Clostridium difficile infection (CDI) among hospital inpatients.


A before-and-after quality improvement intervention comparing 12-month baseline and intervention periods.


A 694-bed teaching hospital.


We administered a multispecies probiotic comprising L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2) to eligible antibiotic recipients within 12 hours of initial antibiotic receipt through 5 days after final dose. We excluded (1) all patients on neonatal, pediatric and oncology wards; (2) all individuals receiving perioperative prophylactic antibiotic recipients; (3) all those restricted from oral intake; and (4) those with pancreatitis, leukopenia, or posttransplant. We defined CDI by symptoms plus C. difficile toxin detection by polymerase chain reaction. Our primary outcome was hospital-onset CDI incidence on eligible hospital units, analyzed using segmented regression.


The study included 251 CDI episodes among 360,016 patient days during the baseline and intervention periods, and the incidence rate was 7.0 per 10,000 patient days. The incidence rate was similar during baseline and intervention periods (6.9 vs 7.0 per 10,000 patient days; P=.95). However, compared to the first 6 months of the intervention, we detected a significant decrease in CDI during the final 6 months (incidence rate ratio, 0.6; 95% confidence interval, 0.4–0.9; P=.009). Testing intensity remained stable between the baseline and intervention periods: 19% versus 20% of stools tested were C. difficile positive by PCR, respectively. From medical record reviews, only 26% of eligible patients received a probiotic per the protocol.


Despite poor adherence to the protocol, there was a reduction in the incidence of CDI during the intervention, which was delayed ~6 months after introducing probiotic for primary prevention.

Infect Control Hosp Epidemiol 2018;765–770


Corresponding author

Address correspondence to William E. Trick, MD, Collaborative Research Unit, 1900 W Polk Street, Ste 1600, Chicago, IL 60612 (


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1. Pronovost, P, Needham, D, Berenholtz, S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. New Engl J Med 2006;355:27252732.
2. Gerding, DN, Muto, CA, Owens, RC. Measures to control and prevent Clostridium difficile infection. Clin Infect Dis 2008;46:S43S49.
3. Trick, WE, Temple, RS, Chen, D, Wright, MO, Solomon, SL, Peterson, LR. Patient colonization and environmental contamination by vancomycin-resistant enterococci in a rehabilitation facility. Arch Phys Med Rehab 2002;83:899902.
4. Sethi, AK, Al-Nassir, WN, Nerandzic, MM, Donskey, CJ. Skin and environmental contamination with vancomycin-resistant enterococci in patients receiving oral metronidazole or oral vancomycin treatment for Clostridium difficile–associated disease. Infect Control Hosp Epidemiol 2009;30:1317.
5. McDonald, LC, Owings, M, Jernigan, DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996–2003. Emerg Infect Dis 2006;12:409415.
6. Dubberke, ER, Gerding, DN, Classen, D, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals. Infect Control Hosp Epidemiol 2008;29(Suppl 1):S81S92.
7. Stelfox, HT, Bates, DW, Redelmeier, DA. Safety of patients isolated for infection control. JAMA 2003;290:18991905.
8. Johnson, S, Clabots, CR, Linn, FV, Olson, MM, Peterson, LR, Gerding, DN. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97100.
9. Goldenberg, JZ, Ma, SS, Saxton, JD, et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea in adults and children. Cochrane Libr 2013.
10. Lau, CS, Chamberlain, RS. Probiotics are effective at preventing Clostridium difficile–associated diarrhea: a systematic review and meta-analysis. Int J Gen Med 2016;9:2737.
11. Johnson, S, Maziade, PJ, McFarland, LV, et al. Is primary prevention of Clostridium difficile infection possible with specific probiotics? Int J Infect Dis 2012;16:786792.
12. Beausoleil, M, Fortier, N, Guenette, S, et al. Effect of a fermented milk combining Lactobacillus acidophilus CL1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Canad J Gastroenterol 2007;21:732736.
13. Sampalis, J, Psaradellis, E, Rampakakis, E. Efficacy of BioK+ CL1285 in the reduction of antibiotic-associated diarrhea–a placebo-controlled double-blind randomized, multi-center study. Arch Med Sci 2010;6:5664.
14. Gao, XW, Mubasher, M, Fang, CY, Reifer, C, Miller, LE. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol 2010;105:16361641.
15. Maziade, P-J, Andriessen, J, Pereira, P, Currie, B, Goldstein, E. Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital. Curr Med Res Opin 2013;29:13411347.
16. Goldstein, EJ, Citron, DM, Claros, MC, Tyrrell, KL. Bacterial counts from five over-the-counter probiotics: are you getting what you paid for? Anaerobe 2014;25:14.
17. McDonald, LC, Coignard, B, Dubberke, E, Song, X, Horan, T, Kutty, PK. Recommendations for surveillance of Clostridium difficile–associated disease. Infect Control Hosp Epidemiol 2007;28:140145.
18. Longtin, Y, Paquet-Bolduc, B, Gilca, R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of c difficile infections: a quasi-experimental controlled study. JAMA Intern Med 2016;176:796804.
19. Song, X, Srinivasan, A, Plaut, D, Perl, TM. Effect of nosocomial vancomycin-resistant enterococcal bacteremia on mortality, length of stay, and costs. Infect Control Hosp Epidemiol 2003;24:251256.
20. Averill, RF, McCullough, EC, Goldfield, N, Hughes, JS, Bonazelli, J, Bentley, L. 3M APR DRG classification system: methodology overview. Agency for Healthcare Research and Quality website. Published 2013. Accessed July 6, 2017.
21. Hernan, MA, Robins, JM. Per-protocol analyses of pragmatic trials. New Engl J Med 2017;377:13911398.
22. Weber, DJ, Rutala, WA, Miller, MB, Huslage, K, Sickbert-Bennett, E. Role of hospital surfaces in the transmission of emerging health care-associated pathogens: norovirus, Clostridium difficile, and Acinetobacter species. Am J Infect Control 2010;38:S25S33.
23. Samore, MH, Venkataraman, L, DeGirolami, PC, Arbeit, RD, Karchmer, AW. Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea. Am J Med 1996;100:3240.
24. Halpin, AL, McDonald, LC. The dawning of microbiome remediation for addressing antibiotic resistance. Clin Infect Dis 2016;62:14871488.
25. Freedberg, DE, Salmasian, H, Cohen, B, Abrams, JA, Larson, EL. Receipt of antibiotics in hospitalized patients and risk for Clostridium difficile infection in subsequent patients who occupy the same bed. JAMA Intern Med 2016;176:18011808.
26. Aroutcheva, A, Auclair, J, Frappier, M, et al. Importance of molecular methods to determine whether a probiotic is the source of lactobacillus bacteremia. Probiot Antimicrob Prot 2016;8:3140.
27. McFarland, LV, Huang, Y, Wang, L, Malfertheiner, P. Systematic review and meta-analysis: multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events. United Eur Gastroen J 2015;4:546561.
28. Johnston, BC, Ma, SS, Goldenberg, JZ, et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea: a systematic review and meta-analysis. Ann Intern Med 2012;157:878888.


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