A multicentre randomised controlled trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea in older people admitted to hospital: the PLACIDE study protocol

Abstract

BackgroundAntibiotic associated diarrhoea complicates 5–39% of courses of antibiotic treatment. Major risk factors are increased age and admission to hospital. Of particular importance is C. difficile associated diarrhoea which occurs in about 4% of antibiotic courses and may result in severe illness, death and high healthcare costs. The emergence of the more virulent 027 strain of C. difficile has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora.MethodsThis study aims to test the hypothesis that administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhoea. We have designed a prospective, parallel group trial where people aged 65 years or more admitted to hospital and receiving one or more antibiotics are randomly allocated to receive either one capsule of the probiotic or a matching placebo daily for 21 days. The primary outcomes are the frequency of antibiotic associated and C. difficile diarrhoea during 8–12 weeks follow-up. To directly inform routine clinical practice, we will recruit a sufficient number of patients to demonstrate a 50% reduction in the frequency of C. difficile diarrhoea with a power of 80%. To maximize the generalizability of our findings and in view of the well-established safety record of probiotics, we will recruit a broad range of medical and surgical in-patients from two different health regions within the UK.DiscussionAntibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control C. difficile diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals.Trial registrationInternational Standard Randomised Controlled Trial Number Register ISRCTN70017204.

The Use of Probiotic Strains in Caries Prevention: A Systematic Review

“…All studies meeting the inclusion criteria then went to a validity assessment. Studies rejected at this or subsequent stages are reported in the Table 1 of excluded studies with the reasons for exclusion [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82]. For each trial, the following information was recorded: citation details; participants: including demographic characteristics and criteria for inclusion; intervention: including type and duration of intervention, duration of follow-up and method of administration.…”

Effect of probiotics on the expression of Barrett’s oesophagus biomarkers

“…For example, inflammatory cytokines are released in oesophageal epithelial injuries, which induce and activate NF-kB and interleukins (1b, 4, 8, 10, 12, and 18) to interconnect in a multiple pathway (Babar et al, 2012). In addition, COX2, which is a tumour-promoting factor, is induced by TNFa and growth factors to accelerate tumourgenesis (Allen et al, 2012;Hashimoto, 2012). These procedures continue during carcinogenesis in association with the activation of p53 and also the induction of CDX genes.…”

Sample Size Considerations in Clinical Trials When Comparing Two Interventions Using Multiple Co-Primary Binary Relative Risk Contrasts

“…We illustrate the methodology with an example from the PLACIDE study (Allen et al, 2012; Allen et al, 2013) described in the Introduction. Recall that the study was designed to evaluate if the administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhea.…”

“…For example, PLACIDE is a randomized double-blinded, parallel group, placebo-controlled clinical trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhea in older people admitted to hospital (Allen et al, 2012; Allen et al, 2013). The trial was designed to demonstrate that the administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment, prevents antibiotic associated diarrhea.…”