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

Samford Wong; Shashivadan P Hirani; Alastair Forbes; Naveen Kumar; Ramaswamy Hariharan; Jean O'Driscoll; Anand Viswanathan; Graham Harvey; Ravi Sekhar; Ali Jamous

doi:10.1016/j.eclinm.2021.101098

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

EClinicalMedicine. 2021 Sep 11:40:101098. doi: 10.1016/j.eclinm.2021.101098. eCollection 2021 Oct.

Authors

Samford Wong^{1

2

3}, Shashivadan P Hirani², Alastair Forbes⁴, Naveen Kumar⁵, Ramaswamy Hariharan⁶, Jean O'Driscoll⁷, Anand Viswanathan⁶, Graham Harvey⁵, Ravi Sekhar⁸, Ali Jamous³

Affiliations

¹ National Spinal Injuries Centre, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom.
² School of Health Sciences, City, University of London, London, United Kingdom.
³ Royal Buckinghamshire Hospital, Aylesbury, United Kingdom.
⁴ University of Tartu, Estonia, and Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
⁵ Midland Centre for Spinal Injury, Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, United Kingdom.
⁶ The Princess Royal Spinal Injuries Centre, Northern General Hospital, Herries Rd, United Kingdom.
⁷ Department of Microbiology, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom.
⁸ Department of Gastroenterology, Stoke Mandeville Hospital, Mandeville Rd, United Kingdom.

Abstract

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 × 10⁹ 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.

Keywords: Antibiotic Associated Diarrhoea; Clostridioides Difficile; Malnutrition; Probiotics; Proton Pump Inhibitor; Spinal Cord Injury.