Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trialBMJ 2007; 335 doi: https://doi.org/10.1136/bmj.39231.599815.55 (Published 12 July 2007) Cite this as: BMJ 2007;335:80
- Mary Hickson, research dietitian1,
- Aloysius L D'Souza, research fellow2,
- Nirmala Muthu, research nurse3,
- Thomas R Rogers, professor of clinical microbiology and honorary consultant (Hammersmith Hospitals NHS Trust)4,
- Susan Want, clinical scientist5,
- Chakravarthi Rajkumar, senior lecturer2,
- Christopher J Bulpitt, professor of geriatric medicine2
- 1Nutrition and Dietetic Research Group, Faculty of Medicine, Imperial College, London W12 0HS
- 2Medicine for the Elderly, Faculty of Medicine, Imperial College, London
- 3Hillingdon Hospital, Uxbridge
- 4Department of Infectious Diseases and Immunity, Faculty of Medicine, Imperial College School of Medicine, London
- 5Microbiology Department, Hammersmith Hospital NHS Trust, London
- Correspondence to: M Hickson email@example.com
- Accepted 11 May 2007
Objective To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.
Design Randomised double blind placebo controlled study.
Participants 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.
Intervention Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.
Main outcome measures Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.
Results 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).
Conclusion Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.
Trial registration National Research Register N0016106821.
We thank Winston Banya for statistical advice and conducting the randomisation; Sheila Bacon, Paula Brown, and Linda Wedlake for assistance with data collection; Edward Pawley, Lucy O'Driscoll, Regina Storch, Kuldip Dehal, and the pharmacy departments at each hospital for management and dispensing of the study drinks; the nursing staff on all the wards involved for help with keeping stool charts, monitoring patients, and collecting stool samples; Manfred Almeida and the staff in the division of microbiology, Hammersmith Hospitals Trust, for help with lactobacilli counts and C difficile toxin tests; and Ruth Peters for organising data entry.
Contributors: ALD'S, MH, CJB, CR, SW, and TRR were all involved in the preparation of the protocol; ALD'S, CJB, and MH obtained ethical approval; ALD'S, CJB, CR, and TRR obtained funding; MH, NM, and ALD'S recruited patients and collected data; MH managed the running of the trial; TRR set up and SW undertook the microbiological investigations; MH and ALD'S undertook data cleaning and analysis with the assistance of CR and CJB; all authors assisted in the production of the manuscript and interpretation of the results and all approved the final version. MH is guarantor.
Funding: Healthcare Foundation and Hammersmith Hospital Trustees research committee and Danone Vitapole (Paris, France). The Healthcare Foundation made initial comments on the design of the study. Once funding was agreed none of the funding sources had any role in the data collection, analysis, interpretation of data, writing of the report, or the decision to submit the paper for publication.
Competing interests: CJB, MH, and ALD'S have received funding from Danone to attend Danone International Conventions on Probiotics. CJB is a member of Danone UK advisory group.
Ethical approval: London multicentre research ethics committee.
- Accepted 11 May 2007