title: 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: BACKGROUND
  Antibiotic 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.
  
  
  METHODS
  This 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.
  
  
  CONCLUSIONS
  Antibiotic 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.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial Number Register ISRCTN70017204.
authors.affiliation: Swansea University, Singleton Park, Swansea, SA2 8PP, UK. s.j.allen@swansea.ac.uk
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Kathie
authors.initials: K
authors.lastname: Wareham
authors.forename: Caroline
authors.initials: C
authors.lastname: Bradley
authors.forename: Wyn
authors.initials: W
authors.lastname: Harris
authors.forename: Anjan
authors.initials: A
authors.lastname: Dhar
authors.forename: Helga
authors.initials: H
authors.lastname: Brown
authors.forename: Alwyn
authors.initials: A
authors.lastname: Foden
authors.forename: Way Yee
authors.initials: WY
authors.lastname: Cheung
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gravenor
authors.forename: Sue
authors.initials: S
authors.lastname: Plummer
authors.forename: Ceri J
authors.initials: CJ
authors.lastname: Phillips
authors.forename: Dietrich
authors.initials: D
authors.lastname: Mack
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001644:Bifidobacterium / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002214:Capsules / Q000008:administration & dosage; D002985:Clinical Protocols; D003015:Clostridium Infections / Q000139:chemically induced / Q000517:prevention & control*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D006761:Hospitals; D006801:Humans; D007297:Inpatients; D007778:Lactobacillus / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D019936:Probiotics / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents; D002214:Capsules; D010919:Placebos