Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years)
inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile,
AAD can result in life-threatening illness. Although underlying disease mechanisms
are not well understood, microbial preparations have been assessed in the prevention
of AAD. However, studies have been mostly small single-centre trials with varying
quality, providing insufficient data to reliably assess effectiveness. We aimed to
do a pragmatic efficacy trial in older inpatients who would be representative of those
admitted to National Health Service (NHS) and similar secondary care institutions
and to recruit a sufficient number of patients to generate a definitive result.
We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy
trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral
antibiotics. A computer-generated randomisation scheme was used to allocate participants
(in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria,
with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo.
Patients, study staff, and specimen and data analysts were masked to assignment. The
primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD)
within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This
trial is registered, number ISRCTN70017204.
Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation
group and 1488 to the placebo group. 1470 and 1471, respectively, were included in
the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%)
participants in the microbial preparation group and 153 (10·4%) participants in the
placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon
cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group
and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35).
578 (19·7%) participants had one or more serious adverse event; the frequency of serious
adverse events was much the same in the two study groups and none was attributed to
participation in the trial.
We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria
was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology
of AAD is needed to guide future studies.
Health Technology Assessment programme; National Institute for Health Research, UK.
Copyright © 2013 Allen et al. Open Access article distributed under the terms of CC
BY. Published by Elsevier Ltd. All rights reserved.