A multicentre, randomised, placebo controlled trial of lactic acid bacteria in prevention of antibiotic-associated diarrhoea (AAD) & Clostridium difficile diarrhoea (CDD) in patients aged 65 years & over admitted to hospital and receiving antibiotics

DESIGN: A multicentre, randomised, placebo-controlled, double blind trial. SETTING: All in-patient wards admitting adult patients at Singleton and Morriston hospitals, Swansea NHS Trust (total 1450 beds) and Medical and Care of the Elderly wards at the University Hospital of North Durham, Bishop Auckland General Hospital and Darlington Memorial Hospital, County Durham & Darlington Acute Hospitals (CDDAH) NHS Trust (598 beds). TARGET POPULATION: People aged 65 years and over admitted to hospital without diarrhoea and already receiving or now prescribed one or more antibiotics. Patients with severe debility, significant immunosuppression and disseminated cancer will be excluded. In 2005/6 (12 months), 26,692 people aged 65 years or greater were admitted in Swansea and 21,676 in CDDAH. 30-37% of patients received antibiotics. The majority of stool specimens positive for C. difficile toxin were in older patients on antibiotics. 432 stool samples were positive for C. difficile toxin in Swansea and 531 in CDDAH (total of 963 cases of CDD across the two sites in 2005/6). HEALTH TECHNOLOGIES BEING ASSESSED: A preparation containing high numbers of four strains of live lactobacilli of human origin. MEASUREMENT OF OUTCOMES AND COST: All clinical, laboratory and research methods will be uniform across the centres involved in the study. Project nurses will visit each ward 7 days/week to identify eligible patients and invite them to join the study. Patients in whom signed, informed consent is obtained will be assigned the next unique patient identification number. Each patient identification number will have been assigned at random to either the probiotic or identical placebo group on a 1:1 basis. Project nurses will review participants daily during admission to identify new cases of diarrhoea, ask about gastrointestinal symptoms (abdominal pain, bloating, flatus, nausea), acceptability and adverse effects of the interventions. All participants will be followed-up for a total of 8 weeks after stopping antibiotics. After discharge, follow-up will be weekly by telephone call or home visit. Diarrhoea is defined as the occurrence of 3 or more loose stools (stools which take the shape of their container) in a 24 hour period. AAD is defined as diarrhoea without pathogens detected on routine laboratory analysis and negative for C. difficile toxin. CDD is defined as diarrhoea with stools positive for C. difficile A or B toxin. Clinical investigation (e.g. sigmoidoscopy), the requirement for medical treatment of CDD and need for colectomy will be determined by the usual clinicians caring for the patients. The details of clinical management and results of investigations will be recorded in the participant log. A stool sample for analysis will be obtained by NHS or research staff as soon after the onset of diarrhoea as possible and collected by research nurses at a home visit if diarrhoea develops after discharge. Stools will be analysed by the hospital laboratories for diarrhoeal pathogens (Salmonella sp, Shigella sp, Campylobacter, E Coli 0157, wet film for ova, cysts and parasites) and for C. difficile toxins A and B using the Biostat EIA test. Stool samples will be repeated if negative for pathogens and C. difficile toxin on initial testing.