PMID- 34541475 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220426 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 40 DP - 2021 Oct TI - A study into the effect of Lactobacillus casei Shirota in preventing antibiotic associated diarrhoea including Clostridioides difficile infection in patients with spinal cord injuries: a multicentre randomised, double-blind, placebo-controlled trial. PG - 101098 LID - 10.1016/j.eclinm.2021.101098 [doi] LID - 101098 AB - BACKGROUND: Antibiotic Associated Diarrhoea (AAD) and Clostridioides Difficile Infection (CDI) are of major concern in spinal cord injury (SCI) rehabilitation. METHODS: A multi-centre, randomized, double-blind, placebo-controlled (the ECLISP) trial, was conducted in three tertiary spinal cord injury centre in the UK to assess the efficacy of consuming a probiotic beverage containing at least 6.5 x 10(9) live Lactobacillus casei Shirota (LcS) in preventing AAD and CDI and in patients with SCI and to determine whether proton pump inhibitors (PPI) and under nutrition-risk are risk factors for AAD/CDI. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. Follow up was set at 7 and 30 days after the antibiotic course finished. The primary outcome was occurrence of AAD up to 30 days after finishing LcS/placebo. This trial is completed and registered (ISRCTN:13119162). FINDINGS: Between November 2014, and November 2019, 359 consenting adult SCI patients (median age: 53.3; range: 18-88 years), from 3 SCI centres responsible for providing approximate 45-50% of UK SCI service, with a requirement for antibiotics due to infection were randomly allocated to receive LcS (n = 181) or placebo (n = 178). Overall, no statistical difference was seen in occurrence of the primary outcomes of AAD at 30 days follow up (45% v 42.1%, RR: 1.071, 0.8-1.4, p = 0.639). In the secondary analyses LcS was associated with a lower risk of AAD at 7 (19% v 35.7%, RR: 0.53, 0.29-0.99, p = 0.040) and 30 days follow up (28% v 52.2%, RR: 0.54, 0.32-0.91, p = 0.015) in the participants who took PPI regularly. Under nutrition-risk was associated with an increased risk of AAD at 7 (RR: 1.76, 1.28-2.44) and 30 days follow up (RR: 1.69, 1.30-2.0). No intervention-related adverse events were reported during the study. INTERPRETATION: The present study indicates that LcS could not prevent AAD/CDI in unselected SCI patients. LcS might have the potential to prevent AAD in the higher risk group of patients on regular PPI. Confirmatory studies are needed to allow translation of this apparent therapeutic success into improved clinical outcomes. FUNDING: Yakult Honsha Co., Ltd. CI - Crown Copyright (c) 2021 Published by Elsevier Ltd. FAU - Wong, Samford AU - Wong S AD - National Spinal Injuries Centre, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom. AD - School of Health Sciences, City, University of London, London, United Kingdom. AD - Royal Buckinghamshire Hospital, Aylesbury, United Kingdom. FAU - Hirani, Shashivadan P AU - Hirani SP AD - School of Health Sciences, City, University of London, London, United Kingdom. FAU - Forbes, Alastair AU - Forbes A AD - University of Tartu, Estonia, and Norwich Medical School, University of East Anglia, Norwich, United Kingdom. FAU - Kumar, Naveen AU - Kumar N AD - Midland Centre for Spinal Injury, Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, United Kingdom. FAU - Hariharan, Ramaswamy AU - Hariharan R AD - The Princess Royal Spinal Injuries Centre, Northern General Hospital, Herries Rd, United Kingdom. FAU - O'Driscoll, Jean AU - O'Driscoll J AD - Department of Microbiology, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom. FAU - Viswanathan, Anand AU - Viswanathan A AD - The Princess Royal Spinal Injuries Centre, Northern General Hospital, Herries Rd, United Kingdom. FAU - Harvey, Graham AU - Harvey G AD - Midland Centre for Spinal Injury, Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, United Kingdom. FAU - Sekhar, Ravi AU - Sekhar R AD - Department of Gastroenterology, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom. FAU - Jamous, Ali AU - Jamous A AD - Royal Buckinghamshire Hospital, Aylesbury, United Kingdom. LA - eng PT - Journal Article DEP - 20210911 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC8435694 OTO - NOTNLM OT - Antibiotic Associated Diarrhoea OT - Clostridioides Difficile OT - Malnutrition OT - Probiotics OT - Proton Pump Inhibitor OT - Spinal Cord Injury COIS- Dr Samford Wong (Chief Investigator) has received funding support from Yakult Honsha Co Ltd. Yakult Europe B.V. provided free LcS/Placebo and the necessary equipment to maintain the cold chain. Prof Alastair Forbes receives honoraria form Fresenius Kabi, Takeda and Dr Falk Pharma. All the other authors have no conflicts to declare. EDAT- 2021/09/21 06:00 MHDA- 2021/09/21 06:01 PMCR- 2021/09/11 CRDT- 2021/09/20 06:21 PHST- 2021/03/19 00:00 [received] PHST- 2021/07/29 00:00 [revised] PHST- 2021/08/09 00:00 [accepted] PHST- 2021/09/20 06:21 [entrez] PHST- 2021/09/21 06:00 [pubmed] PHST- 2021/09/21 06:01 [medline] PHST- 2021/09/11 00:00 [pmc-release] AID - S2589-5370(21)00378-3 [pii] AID - 101098 [pii] AID - 10.1016/j.eclinm.2021.101098 [doi] PST - epublish SO - EClinicalMedicine. 2021 Sep 11;40:101098. doi: 10.1016/j.eclinm.2021.101098. eCollection 2021 Oct.