Original Contribution | Published:

Colon/Small Bowel

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

The American Journal of Gastroenterology volume 105, pages 16361641 (2010) | Download Citation

Abstract

OBJECTIVES:

Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.

METHODS:

In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285® +Lactobacillus casei LBC80R® Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.

RESULTS:

Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.

CONCLUSIONS:

The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , , . Probiotics as prevention and treatment for diarrhea. Curr Opin Gastroenterol 2009;25:18–23.

  2. 2.

    , , . Clostridium difficile colitis. N Engl J Med 1994;330:257–262.

  3. 3.

    , , et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079–1084.

  4. 4.

    . C. difficile hits Sherbrooke, Que., hospital: 100 deaths. CMAJ 2004;171:436.

  5. 5.

    . Clostridium difficile-associated diarrhea: risk factors, diagnostic methods, and treatment. Rev Gastroenterol Disord 2004;4:186–195.

  6. 6.

    , . Clostridium difficile-associated diarrhea in adults. CMAJ 2004;171:51–58.

  7. 7.

    , . Clostridium difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med 2006;73:187–197.

  8. 8.

    , . Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol 2008;14:2650–2661.

  9. 9.

    , , et al. Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study. Arch Intern Med 1996;156:1449–1454.

  10. 10.

    , , et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2007, CD004827.

  11. 11.

    . Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol 2008;3:563–578.

  12. 12.

    , , . The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea. Lancet Infect Dis 2009;9:237–244.

  13. 13.

    , , et al. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 2002;324:1361.

  14. 14.

    . Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812–822.

  15. 15.

    , , . The use of probiotics in the prevention and treatment of antibiotic-associated diarrhea with special interest in Clostridium difficile-associated diarrhea. Nutr Clin Pract 2009;24:33–40.

  16. 16.

    , , . The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA 2001;285:1987–1991.

  17. 17.

    , . Bristol Scale Stool Form. A still valid help in medical practice and clinical research. Tech Coloproctol 2001;5:163–164.

  18. 18.

    , , et al. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Int Microbiol 2004;7:59–62.

  19. 19.

    , , et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;335:80.

  20. 20.

    , , . Probiotics for prevention of antibiotic-associated diarrhea. J Clin Gastroenterol 2008;42 (Suppl 2): S58–S63.

  21. 21.

    , , . Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis 2006;12:409–415.

  22. 22.

    , , et al. Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008;47:56–62.

  23. 23.

    , , et al. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother 2008;52:2403–2406.

  24. 24.

    , , . New issues in infectious diarrhea. Rev Gastroenterol Disord 2005;5 (Suppl 3): S16–S25.

  25. 25.

    , , . Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 2006;83:1256–1264; quiz 1446–7.

  26. 26.

    , , et al. Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review. CMAJ 2005;173:167–170.

Download references

Acknowledgements

We thank Charlie Zhang, MD, and Kelly Zhang, RN, of Sprim Advanced Life Sciences for their help with study conduct and data collection.

Author information

Affiliations

  1. Department of Gastroenterology, Xinhua/Yuyao Hospital, Shanghai, China

    • Xing Wang Gao
    •  & Chong Yu Fang
  2. Sprim Advanced Life Sciences, San Francisco, California, USA

    • Mohamed Mubasher
    • , Cheryl Reifer
    •  & Larry E Miller

Authors

  1. Search for Xing Wang Gao in:

  2. Search for Mohamed Mubasher in:

  3. Search for Chong Yu Fang in:

  4. Search for Cheryl Reifer in:

  5. Search for Larry E Miller in:

Competing interests

Guarantor of the article: Xing Wang Gao, MD.

Specific author contributions: Planning study: Xing Wang Gao, Mohamed Mubasher, Chong Yu Fang, and Cheryl Reifer; conducting study: Xing Wang Gao, Chong Yu Fang, and Cheryl Reifer; collecting data: Xing Wang Gao and Chong Yu Fang; interpreting data: Xing Wang Gao, Mohamed Mubasher, and Larry E. Miller; drafting paper: Xing Wang Gao, Mohamed Mubasher, Cheryl Reifer, and Larry E. Miller; approval of submitted final draft: Xing Wang Gao, Mohamed Mubasher, Chong Yu Fang, Cheryl Reifer, and Larry E. Miller.

Financial support: Bio-K+ International (Laval, Quebec, Canada) provided financial support for this clinical trial. Sprim Advanced Life Sciences helped with study planning, conduct, and analysis and with paper development.

Potential competing interests: None.

Corresponding author

Correspondence to Larry E Miller.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ajg.2010.11

Further reading