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.

Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.

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.

Access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda: a qualitative study.

BACKGROUND: Inappropriate use of antimicrobials in both humans and animals is a key driver of antimicrobial resistance (AMR). In addition, human behaviours such as poor disposal of antimicrobials in the environment can increase their exposure to microbes which can impact on humans and animals. However, evidence on access, use and disposal of antimicrobials for humans and animals at community level in Uganda is limited. This study therefore explored access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda. METHODS: A qualitative study was conducted that involved focus group discussions (FGDs) and key informant interviews (KIIs). Participants of the FGDs were community health workers (CHWs) and farmers involved in animal husbandry, while key informants included: officials from the Ministry of Health; Ministry of Agriculture, Animal Industry and Fisheries; human and animal health professionals; district health officials; and members of the national AMR surveillance committee. Twelve FGDs were held (8 for CHWs and 4 for farmers) while 15 KIIs were conducted. Thematic analysis in NVivo (version 12) was performed. RESULTS: Five main themes emerged from the study: access to antimicrobials in humans; access to antimicrobials in animals; use of antimicrobials in humans; use of antimicrobials in animals; and disposal of antimicrobials. Community members mainly accessed antimicrobials for humans from public health facilities such as government health centres, as well as private facilities, including drug shops and clinics. Antimicrobials for animals were obtained from veterinary practitioners and drug shops (both for humans and veterinary). Examples of inappropriate use of antimicrobials in both humans and animals was evident, such as sharing antibiotics among household members, and giving human-prescribed antimicrobials to food-producing animals as growth promoters. While some CHWs returned unused antimicrobials to public health facilities for proper disposal, community members mainly disposed of antimicrobials with general household waste including dumping in rubbish pits. CONCLUSIONS: There is a need to increase awareness among the population on proper access, use and disposal of antimicrobials for both humans and animals. Development of a drug disposal system at community level would facilitate improved waste management of antimicrobials. Together, these measures would help prevent the rate of progression of AMR in communities.

A One Health Approach to Strengthening Antimicrobial Stewardship in Wakiso District, Uganda.

Antimicrobial stewardship (AMS), as one of the global strategies to promote responsible use of antimicrobials to prevent antimicrobial resistance (AMR), remains poor in many low-and middle-income countries (LMICs). We implemented a project aimed at strengthening AMS in Wakiso district, Uganda using a One Health approach. A total of 86 health practitioners (HPs), including animal health workers, and 227 community health workers (CHWs) participated in training workshops, and over 300 pupils from primary schools were sensitized on AMR, AMS, and infection prevention and control (IPC). We further established two multidisciplinary online communities of practice (CoPs) for health professionals and students, with a current membership of 321 and 162, respectively. In addition, a Medicine and Therapeutics Committee (MTC) was set up at Entebbe Regional Referral Hospital. The project evaluation, conducted three months after training, revealed that the majority of the HPs (92.2%) and CHWs (90.3%) reported enhanced practices, including improved hand washing (57.3% and 81.0%, respectively). In addition, 51.5% of the HPs reported a reduction in the quantity of unnecessary antibiotics given per patient. This project demonstrates that AMS interventions using a One Health approach can promote understanding of the prudent use of antimicrobials and improve practices at health facilities and in communities.

An uncommon cause for a breast abscess: Actinomyces turicensis with Peptoniphilus harei.

Our case report describes a patient with a common presenting complaint yet an uncommon infection. Our patient presented with a fluctuant breast mass diagnosed as a breast abscess. An aspirate sample was sent for culture and sensitivities, which revealed the presence of Actinomyces turicensis and the anaerobe Peptoniphilus harei She was therefore prescribed several weeks of amoxicillin and metronidazole, and made a full recovery. There are only three case reports describing A. turicensis as a causative organism for breast abscess, one of which had also occurred in our department. One case also showed the additional presence of P. harei Our findings reveal a growing need for increasing clinician awareness of A. turicensis and the importance of aspirate sample culture and sensitivity.

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.