Probiotics – Do they reduce the incidence of antibiotic associated diarrhoea (AAD) in adults?
Date First Published:
December 10, 2009
Last Updated:
April 29, 2010
Report by:
Lee Helliwell , SpR Emergency Medicine (Lancashire Teaching Hospital, Preston, UK )
Search checked by:
Catherine Jackson, Lancashire Teaching Hospital, Preston, UK
Three-Part Question:
In [adult patients taking antibiotics] does the [co-administration of probiotics] [reduce the incidence of antibiotic-associated diarrhoea]?
Clinical Scenario:
Your relative has returned from their general practitioner with a prescription for antibiotics. They ask you if there is anything they could take to prevent diarrhoea following the antibiotics, as, on occasions, it has resulted in them stopping the antibiotics early. You have some recollection regarding the use of probiotics and wonder whether there is evidence to support their use in this manner.
Search Strategy:
Medline 1950 - November week 1 2009 using the OvidSP interface
Search Details:
[(exp Anti-Bacterial Agents/OR antibiotic$.mp.) AND (exp Probiotics/OR probiotic$.mp. OR exp Lactobacillus/OR Lactobacill$.mp. OR exp Saccharomyces/OR Saccharomyc$.mp.) AND (exp Clostridium/OR exp Clostridium difficile/OR clostridium difficile.mp. OR exp Diarrhea/OR Diarrh$.mp.)] LIMIT to abstracts and English language and humans and ‘all adult (19 plus years)’. The Cochrane database of systematic reviews.
Outcome:
This MEDLINE search returned 104 papers, of which 13 answered the question.
Of these 13 papers: one was excluded because it was a pilot study, of very small numbers (Safdar et al, 2008); a second was excluded because it pooled data from both adults and paediatric patients (Conway et al, 2007) and three others as they were included in the meta-analysis (Lewis et al, 1998; McFarland et al, 1995 and Gotz et al, 1979).
The Cochrane database of systematic reviews did not return any relevant articles.
Of these 13 papers: one was excluded because it was a pilot study, of very small numbers (Safdar et al, 2008); a second was excluded because it pooled data from both adults and paediatric patients (Conway et al, 2007) and three others as they were included in the meta-analysis (Lewis et al, 1998; McFarland et al, 1995 and Gotz et al, 1979).
The Cochrane database of systematic reviews did not return any relevant articles.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink Wenus C, Goll R, Loken E, et al. 2008 Norway | All adult inpatients that were prescribed antibiotics of at least 7 days duration were randomised to recieve a probiotic milk drink or placebo. | Randomised, double-blind, placebo-controlled study. | Primary end point criterion was diarrhoea, defined as at least three fluid stools/day for at least 2 days during the test period | 87 patients were randomized to probiotic (n=46) or placebo (n=41) treatment. Eight (27.6%) patients in the placebo group, and two (5.9%) patients in the probiotic group experienced AAD (P=0.035). | Small sample size High drop out rate (12 in each group). Calculations based on per-protocol analysis and not intention-to-treat. |
| The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin. Koning C, Jonkers D, Stobberingh E, et al. 2008 Netherlands | 41 healthy volunteers were given 500 mg amoxycillin twice daily for 7 days and were randomized to either 5 g of a multispecies probiotic, Ecologic, or placebo, twice daily for 14 days. | Randomised, double-blind, placebo-controlled study. |
Main outcome measures were intestinal microbiota composition, bowel frequency and consistency according to the Bristol stool scale | Bowel movements with a frequency >or=3 per day for at least 2 days and/or a consistency >or=5 for at least 2 days were reported less frequently in the probiotic compared to the placebo group (48%vs 79%, P < 0.05) | The use of healthy volunteers may not make this study transferable to those acutely unwell. Small sample size. |
| 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 Beausoleil M, Fortier N, Guenette S, et al. 2007 Canada | All hospitalized patients, who were anticipated to take at least three days of any systemic antibiotic, were randomly assigned to receive either a lactobacilli-fermented milk or a placebo. | Randomised, double-blind, placebo-control study. | The primary outcome of the present study was the incidence of AAD during the study period | Among 89 randomized patients, antibiotic-associated diarrhea occurred in seven of 44 patients (15.9%) in the lactobacilli group and in 16 of 45 patients (35.6%) in the placebo group (OR 0.34, 95% CI 0.125 to 0.944; P=0.05). | Hugely underpowered. Large proportion excluded (1306 of 1422 screened). Lack of generalisability of subjects as all hospitalised. |
| Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial Hickson M, D'Souza A, Muthu N, et al. 2007 UK | 135 hospitalised patients taking antibiotics randomised to receive either probiotic drink or placebo. | Randomised, double-blind, placebo-controlled study. | Primary outcome: occurrence of AAD. Secondary outcome: presence of CDAD | 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). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by CDAD (p=0.001) | Analysis did not follow the intention to treat model. High exclusion rate (1625/1760) questioning generalisability. High numbers (16%) lost to follow up. |
| Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: A prospective study Can M, Besirbellioglu B, Avci I, et al. 2006 Turkey | 151 inpatients randomised to recieve antibiotics plus either S. boulardii or placebo |
Randomised, double-blind, placebo-controlled study. | Rate of AAD in both groups | The rate of AAD was 9% in the placebo group and 1.4% in the S. boulardii group (p<0.05) | Outcome measures not defined. No power calculation performed. No consort diagram. No intention to treat model. |
| Meta-analysis: the effect of probiotic administration on antibioticassociated diarrhoea Cremonini F, Di Caro S, Nista E, et al. 2002 Italy | 7 randomised, control studies that included 881 patients. | Meta-analysis | Whether probiotics reduce AAD | Three studies showed significantly less AAD with a combined relative risk of 0.397 (95% CI 0.275 to 0.571) | Studies included children Poor homogeneity |
| Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial. Thomas M, Litin S, Osmon D, et al.(abstract only available). 2001 USA | 302 hospitalised patients recieving antibiotics were randomly allocated to receive Lactobacillus GG or placebo for 14 days. | Prospective, randomised, double-blind, placebo-controlled trial. | Proportion of patients who developed diarrhoea | ADD occurrence rate was 39/133 (29.3%) in those receiving Lactobacillus and 40/134 (29.9%) in those receiving placebo (p=0.93) | Only abstract available from publishers. |
Bottom Line:
The evidence supports probiotics for reducing antibiotic-associated diarrhoea.
References:
- Wenus C, Goll R, Loken E, et al. . Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink
- Koning C, Jonkers D, Stobberingh E, et al. . The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin.
- 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
- Hickson M, D'Souza A, Muthu N, et al. . Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial
- Can M, Besirbellioglu B, Avci I, et al. . Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: A prospective study
- Cremonini F, Di Caro S, Nista E, et al.. Meta-analysis: the effect of probiotic administration on antibioticassociated diarrhoea
- Thomas M, Litin S, Osmon D, et al.(abstract only available).. Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.