Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial

doi:10.1136/bmj.39231.599815.55

BMJ 2007;335:80 (14 July), doi:10.1136/bmj.39231.599815.55 (published 29 June 2007)

Research

Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial

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

¹ Nutrition and Dietetic Research Group, Faculty of Medicine, Imperial College, London W12 0HS, ² Medicine for the Elderly, Faculty of Medicine, Imperial College, London, ³ Hillingdon Hospital, Uxbridge, ⁴ Department of Infectious Diseases and Immunity, Faculty of Medicine, Imperial College School of Medicine, London, ⁵ Microbiology Department, Hammersmith Hospital NHS Trust, London

Correspondence to: M Hickson mhickson@hhnt.nhs.uk

Objective To determine the efficacy of a probiotic drink containingLactobacillus for the prevention of any diarrhoea associatedwith 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 pathologythat could result in diarrhoea, antibiotic use in the previousfour weeks, severe illness, immunosuppression, bowel surgery,artificial heart valves, and history of rheumatic heart diseaseor infective endocarditis.

Intervention Consumption of a 100 g (97 ml) drink containingLactobacillus casei, L bulgaricus, and Streptococcus thermophilustwice a day during a course of antibiotics and for one weekafter the course finished. The placebo group received a longlifesterile milkshake.

Main outcome measures Primary outcome: occurrence of antibioticassociated diarrhoea. Secondary outcome: presence of C difficiletoxin and diarrhoea.

Results 7/57 (12%) of the probiotic group developed diarrhoeaassociated with antibiotic use compared with 19/56 (34%) inthe placebo group (P=0.007). Logistic regression to controlfor other factors gave an odds ratio 0.25 (95% confidence interval0.07 to 0.85) for use of the probiotic, with low albumin andsodium also increasing the risk of diarrhoea. The absolute riskreduction was 21.6% (6.6% to 36.6%), and the number needed totreat 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 ofantibiotic 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.

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Prescribing antibiotics in primary care: Chris Del Mar
BMJ 2007 335: 407-408. [Extract] [Full Text] [PDF]

Data are not widely applicable: Mark H Wilcox and Jonathan A Sandoe
BMJ 2007 335: 171. [Extract] [Full Text] [PDF]

No high risk antibiotics?: Tom Billyard
BMJ 2007 335: 171. [Extract] [Full Text] [PDF]

No proton pump inhibitors?: Mario B Konfortov
BMJ 2007 335: 171. [Extract] [Full Text] [PDF]

Do adverts subvert? Are bacteria good for us?: Douglas Kamerow
BMJ 2007 335: 0. [Extract] [Full Text]

Diarrhoea associated with antibiotic use: Lynne V McFarland
BMJ 2007 335: 54-55. [Extract] [Full Text] [PDF]

Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis: Aloysius L D'Souza, Chakravarthi Rajkumar, Jonathan Cooke, and Christopher J Bulpitt
BMJ 2002 324: 1361. [Abstract] [Full Text] [PDF]

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Monaghan, T, Boswell, T, Mahida, Y R (2008). Recent advances in Clostridium difficile-associated disease. Gut 57: 850-860 [Abstract] [Full text]
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Gould, K., Short, G. (2008). Probiotics and antibiotic-associated diarrhoea--a logical flaw?. J Antimicrob Chemother 61: 761-761 [Full text]
Thompson, I. (2008). Clostridium difficile-associated disease: update and focus on non-antibiotic strategies. Age Ageing 37: 14-18 [Abstract] [Full text]
(2007). Probiotics Prevent C. difficile Diarrhea. JWatch Gastroenterology 2007: 2-2 [Full text]
Mar, C. D. (2007). Prescribing antibiotics in primary care. BMJ 335: 407-408 [Full text]
Wilcox, M. H, Sandoe, J. A (2007). Data are not widely applicable. BMJ 335: 171-171 [Full text]
Billyard, T. (2007). No high risk antibiotics?. BMJ 335: 171-171 [Full text]
Konfortov, M. B (2007). No proton pump inhibitors?. BMJ 335: 171-171 [Full text]
(2007). Lactobacillus Helps Prevent Antibiotic-Related Diarrhea. JWatch General 2007: 2-2 [Full text]
McFarland, L. V (2007). Diarrhoea associated with antibiotic use. BMJ 335: 54-55 [Full text]

Rapid Responses:

Read all Rapid Responses

A prectical approach to prevent diarrhoea associated with antiobiotics and Clostridium difficile: Maria Louise O. Demesa
bmj.com, 3 Jul 2007 [Full text]
milk as a placebo?: vijayashankara nanjegowda
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Effect of PPI?: Mario B Konfortov
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Helicobacter pylori treatment, improved by probiotics.: Enrique J. S�nchez-Delgado, MD, Professor
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Why exclude high risk antibiotics?: Tom Billyard
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yakult or yazoo - What say you, seniore?: sunku h guptha
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Restricting the use of Antibiotics: A cost effective way to prevent antibiotic associated diarrhea: S Kapoor
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Probiotics and the enteric ecosystem !: MOHAMED S. NOSHI,MD,FACP
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Used of probiotic study: lack of appropriate control group: Jeorge M. Orendi
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Antibiotic associated diarrhoea and primary care: Shaun Conway
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Prescribe probiotics?: Sreekanth J Pillai
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Tobacco: potential confounder: Michael K Park
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A win-win intervention: Dr Beena R. Nayak, et al.
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Critical appraisal: ABRAHAM P. GEORGE, et al.
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Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: NAZAR R DESSOUKI
bmj.com, 28 Jul 2007 [Full text]
Author's Reply: Mary Hickson, et al.
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Local incidence of Clostridium difficile associated diarrhoea to be considered.: Jes�s Rodr�guez-Ba�o, et al.
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