The battle of the bugs

1 January 2014

Does taking good bugs (probiotics) keep bad bugs at bay in hospital?


Taking high dose probiotics for 21 days does not prevent antibiotic-associated diarrhoea or Clostridium difficile diarrhoea in stable older adults receiving oral or intravenous antibiotics in hospital.


Efforts to reduce the incidence of hospital-acquired infections have concentrated on hand hygiene, as well as isolation procedures and antibiotic stewardship. Past reviews have also suggested lactobacillus (probiotic) preparations may prevent antibiotic-acquired diarrhoea, but the evidence is based on small trials. A large trial suggests otherwise and necessitates closer review.


Among hospitalised older adults, do probiotics reduce the incidence of antibiotic-associated diarrhoea?


PubMed – Clinical queries: Probiotics AND hospital AND adults AND diarrhoea.


Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Dhar A, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:1249-57.


Two-arm, pragmatic, double-blinded, randomised controlled trial conducted in five hospitals in Wales and England from 2009. 17,420 patients were screened, 3202 were not eligible, 9068 declined to participate, and 2981 were randomised. Included participants were hospitalised adults aged 65 or older who were either about to start or had already had one or more oral or intravenous antibiotics in the previous seven days. Exclusion criteria were existing diarrhoea, immunocompromised to the degree that isolation or barrier precautions required, high dependency or intensive care patient, had prosthetic heart valve, Clostridium difficile diarrhoea in preceding three months, inflammatory bowel disease that needed treatment in previous twelve months, suspected pancreatitis, known abnormality or disease of mesenteric vessels or coeliac axis, jejunal tube present, previous adverse reaction to probiotics, or unwilling to discontinue current use of probiotics.

Intervention (n=1493): Capsule containing lyophilised powder containing 6 x 106 live bacteria from two strains of Lactobacillus acidophilus and two strains of bifidobacterium (B. bifidum and B. lactis) once daily for 21 days.

Control (n=1488): Capsule containing maltodextrin powder once daily for 21 days.


Primary outcome measures were occurrence of antibiotic-associated diarrhoea (AAD) or Clostridium difficile diarrhoea (CDD), with diarrhoea defined as three or more loose stools in a 24 hour period. Stool samples were collected during episodes of diarrhoea. Secondary outcomes included severity and duration of diarrhoea, abdominal symptoms, serious adverse events, duration of hospital stay, acceptability of the microbial preparation, and quality of life .


Randomisation – computer-generated randomisation using variable sized blocks, stratified by study centre; Allocation concealment – not described, but likely to have been addressed through blinding mechanism. Complete follow-up – almost complete follow-up with only 40 lost or excluded from analysis (1.3per cent); Intention-to-treat analysis – modified intention-to-treat analysis with a small number (1.5 and 1.1per cent in each group) excluded from the analysis because the allocated intervention was not known (labelling error), the participant did not receive the intervention, or was lost to follow-up; Blinding – participants, study staff, and analysts were blinded to assignment; Equal treatment – appears equal on type, number and duration of antibiotic use; Baseline comparability – appears equal on demography, source of admission, smoking and alcohol use, previous admissions and comorbidity. Overall impression is that it was a high quality study.


Mean age of participants was 77 years. About 49 per cent of participants were female, more than 90 per cent had been admitted from own home, and about one third had been in hospital within the previous eight weeks. About 4 per cent had taken probiotics or yoghurt within the previous two weeks prior to the trial. The incidence of AAD was 10.6 per cent and the incidence of CDD was 1.0 per cent. There was no difference between the groups (table below). The median duration of hospitalisation was four days and no different between the groups. The incidence of serious adverse event (death, life-threatening event, prolonged hospitalisation, or other serious medical event) was 19.7 per cent, no different between groups and no serious adverse event was ascribed to the treatment.


Trial funded by NIHR Health Technology Assessment programme and registered on the ISRCTN WHO-compliant trials registry.

Previous systematic reviews have suggested probiotics prevent AAD or CDD. Although this trial finds no effect for probiotics, when added to meta-analysis from those previous reviews, the meta-analysis still suggested probiotics reduce diarrhoea in older adults. Raises the question of what evidence to believe – a meta-analysis of small poor quality trials or a large trial?

Reviewer: Dr Andrew Jull, RN PhD, Associate Professor, University of Auckland & Nurse Advisor – Quality & Safety, Auckland District Health Board.