Article Text

A probiotic drink prevented diarrhoea and Clostridium difficile–associated diarrhoea in older patients taking antibiotics

Statistics from

M Hickson

Dr M Hickson, Charing Cross Hospital, London, UK; mary.hickson{at}


Does a probiotic drink prevent diarrhoea and Clostridium difficile–associated diarrhoea in older adults receiving antibiotics in hospital?



randomised controlled trial (RCT).




blinded (patients, {clinicians, data collectors, outcome assessors, data analysts, monitoring committee}*).

Follow-up period:

4 weeks after discharge.


3 hospitals in London, UK.


135 patients >50 years of age (mean age 74 y, 54% women) who were receiving antibiotics (single or multiple, oral or intravenous) and were able to take food and drinks. Exclusion criteria included diarrhoea on admission or recurrent diarrhoea; bowel pathology that could cause diarrhoea; intake of high-risk antibiotics (ie, clindamycin, cephalosporins, or aminopenicillins) or >2 courses of other antibiotics in the past 4 weeks; severe life-threatening illness; immunosuppression; bowel surgery; artificial heart valve; history of rheumatic heart disease or infective endocarditis; probiotic treatment before admission; and intolerance to lactose or dairy products.


100 g of probiotic yoghurt drink (Actimel, Danone, France) (n = 69) or a sterile milkshake (n = 66) twice daily, 30 minutes before or 1–2 hours after meals. The probiotic drink contained L casei (1.0 x 108 colony-forming units [cfu]/ml), S thermophilus (1.0 x 108 cfu/ml), and L bulgaricus (1.0 x 107 cfu/ml). The drinks were started ⩽48 hours after starting antibiotic treatment and stopped 1 week after the end of treatment.


diarrhoea (>2 liquid stools/d for ⩾3 d in quantities exceeding normal). Secondary outcome was C difficile infection (an episode of diarrhoea and detection of toxins A and/or B from a stool sample)

Patient follow-up:

84% (intention-to-treat analysis).


The probiotic group had fewer episodes of antibiotic- and C difficile–associated diarrhoea than the placebo group (table). No patients in the probiotic group tested positive for C difficile toxins (table).

Probiotic drink v sterile milkshake to prevent antibiotic- and Clostridium difficile–associated diarrhoea in older inpatients*


A probiotic drink prevented antibiotic- and Clostridium difficile–associated diarrhoea in older adults receiving antibiotics in hospital.

*Information provided by author.

A modified version of this abstract appears in Evidence-Based Medicine.


Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;335:80.

Clinical impact ratings: General/Internal medicine 6/7; Infectious disease 5/6


Diarrhoea is a common side effect in patients receiving antibiotics. Although multiple pathogens have been identified as causative agents for diarrhoea, C difficile accounts for up to 25% of all cases, with an estimated incidence of 7 cases per 10 000 patient-days.1 Probiotics containing bacteria or yeast are intended to replenish the body’s naturally occurring intestinal microflora that is reduced by antibiotics. However, the therapeutic value of probiotics to prevent opportunistic infections subsequent to antibiotic use remains equivocal. A meta-analysis concluded that probiotics are beneficial in preventing antibiotic-associated diarrhoea (relative risk 0.40, 95% CI 0.27 to 0.57),2 although included studies did not use a placebo design. Another review of 25 RCTs found that Saccaromyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures reduced risk of antibiotic-associated diarrhoea, although only S boulardii was effective for C difficile–related diarrhoea.3 On the other hand, intention-to-treat analysis of 10 RCTs of children found non-significant results.4

The trial by Hickson et al compared a probiotic Lactobacillus preparation with placebo for the prevention of antibiotic-associated diarrhoea and found a significant reduction in diarrhoea caused by antibiotic use or C difficile. The groups were comparable, with a substantial proportion of patients classified as high risk (ie, received aminopenicillin or cephalosporins). However, the bottles that contained the probiotics and placebo were not identical; nurses dispensed the treatment and recorded diarrhoea. Being aware of treatment assignment could lead to bias, although the authors considered this possibility a low risk. The greater threat to the integrity of the findings was loss to follow-up (16%), as these patients were excluded from the analysis. However, the loss was balanced between both groups (17% v 15%). Overall, this is a well-designed and executed study.

The potential cost savings of preventing C difficile–related diarrhoea are impressive: costs were US$120 for probiotic use compared with US$3669 for management of C difficile–diarrhoea, and only 5 patients would need to be treated with probiotics to prevent 1 case of antibiotic-associated diarrhoea. Probiotic bacteria have strain-specific action. Routine administration of strain-specific probiotics with antibiotics in older patients is justifiable.

View Abstract


  • Source of funding: Health Foundation and Hammersmith Hospital Trustees Research Committee, and Danone Vitapole.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.