Lactobacillus casei Shirota probiotic drinks reduce antibiotic associated diarrhoea in patients with spinal cord injuries who regularly consume proton pump inhibitors: a subgroup analysis of the ECLISP multicentre RCT.

STUDY DESIGN: This was a sub-group analysis of a multicentre, randomised, placebo-controlled, double-blind trial (ECLISP trial) OBJECTIVES: To assess the efficacy of a probiotic containing at least 6.5 × 109 live Lactobacillus casei Shirota (LcS) in preventing antibiotic associated diarrhoea (AAD) in patients with spinal cord injury (SCI) who consumed proton pump inhibitor (PPI) regularly. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. The trial was registered with ISRCTN:13119162. SETTING: Three SCI centres (National Spinal Injuries Centre, Midland Centre for Spinal Injuries and Princess Royal Spinal Cord Injuries Centre) in the United Kingdom METHODS: Between November 2014, and November 2019, 95 eligible consenting SCI patients (median age: 57; IQ range: 43-69) were randomly allocated to receive LcS (n = 50) or placebo (n = 45). The primary outcome is the occurrence of AAD up to 30 days after finishing LcS/placebo. RESULTS: The LcS group had a significantly lower incidence of AAD at 30 days after finishing the antibiotic course (28.0 v 53.3%, RR: 95% CI: 0.53, 0.31-0.89; z = 2.5, p = 0.01). Multivariate logistic regression analysis identified that LcS can reduce the risk of AAD at 30 days (OR: 0.36, 95% CI 0.13, 0.99, p < 0.05). No intervention-related adverse events were reported during the study. CONCLUSIONS: LcS has the potential to prevent AAD in what could be considered a defined vulnerable group of SCI patients on regular PPI. A confirmatory, randomised, placebo-controlled study is needed to confirm this apparent therapeutic success to translate it into appropriate clinical outcomes. SPONSORSHIP: Yakult Honsha Co., Ltd.

A Lactobacillus casei Shirota probiotic drink reduces antibiotic-associated diarrhoea in patients with spinal cord injuries: a randomised controlled trial.

Certain probiotics may prevent the development of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD), but their effectiveness depends on both strain and dose. There are few data on nutritional interventions to control AAD/CDAD in the spinal cord injury (SCI) population. The present study aimed to assess (1) the efficacy of consuming a commercially produced probiotic containing at least 6·5 × 109 live Lactobacillus casei Shirota (LcS) in reducing the incidence of AAD/CDAD, and (2) whether undernutrition and proton pump inhibitors (PPI) are risk factors for AAD/CDAD. A total of 164 SCI patients (50·1 (sd 17·8) years) with a requirement for antibiotics (median 21 d, range 5-366) were randomly allocated to receive LcS (n 76) or no probiotic (n 82). LcS was given once daily for the duration of the antibiotic course and continued for 7 days thereafter. Nutritional risk was assessed by the Spinal Nutrition Screening Tool. The LcS group had a significantly lower incidence of AAD (17·1 v. 54·9%, P< 0·001). At baseline, 65% of patients were at undernutrition risk. Undernutrition (64·1 v. 33·3%, P< 0·01) and the use of PPI (38·4 v. 12·1 %, P= 0·022) were found to be associated with AAD. However, no significant difference was observed in nutrient intake between the groups. The multivariate logistic regression analysis identified poor appetite ( < 1/2 meals eaten) (OR 5·04, 95% CI 1·28, 19·84) and no probiotic (OR 8·46, 95% CI 3·22, 22·20) as the independent risk factors for AAD. The present study indicated that LcS could reduce the incidence of AAD in hospitalised SCI patients. A randomised, placebo-controlled study is needed to confirm this apparent therapeutic success in order to translate into improved clinical outcomes.

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.

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.

Effectiveness of probiotic in preventing and treating antibiotic-associated diarrhoea and/or Clostridium difficile-associated diarrhoea in patients with spinal cord injury: a protocol of systematic review of randomised controlled trials.

BACKGROUND: Probiotics may prevent antibiotic-associated and Clostridium difficile-associated diarrhoea (AAD/CDAD). Many spinal cord injury centre (SCIC) practitioners consider probiotics generically and may not realise that efficacy can be strain-, dose- and disease-specific. In order to confirm these effects and fully evaluate the extent of probiotic effectiveness in these patients, a systematic review and meta-analysis is indicated. METHODS: The following databases will be searched for relevant studies: Cochrane Library; Centre for Reviews and Dissemination (CRD) Database; CINAHL; PsycINFO; Embase; Medline; AMED; International Clinical Trials Registry Platform Search Portal and ISRCTN Registry and will hand search a list of conference proceedings. Any randomised controlled trials without restriction of publication status will be included with treatment of AAD/CDAD. Outcomes will include the effect of probiotic on the occurrence of AAD/CDAD and duration of diarrhoea, intensive care unit admission, hospital mortality and length of hospital stay. Two reviewers will independently screen the titles, abstracts or even full texts and extract data. Two other reviewers will assess study quality. Revman 5.1 software will be used to conduct meta-analysis and calculate the risk ratio for dichotomous data. Weighted mean difference or standard mean difference will be calculated for continuous data. The Cochrane Collaboration's tool will be used to assess the risk of bias. DISCUSSION: This systematic review protocol will provide information on probiotic therapy for AAD and CDAD in spinal cord injury (SCI) population. The results will be disseminated through peer-reviewed publication or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015016976.