Epidemiology of Escherichia coli bloodstream infection antimicrobial resistance trends across South West England during the first 2 years of the coronavirus disease 2019 pandemic response.

OBJECTIVES: Between 2016 and 2019, the proportion of Escherichia coli bloodstream infection (BSI) with resistance to at least one antibiotic increased nationally. Public health interventions implemented in response to the COVID-19 pandemic changed population contact patterns and healthcare systems, with consequent effects on epidemiological trends of numerous pathogens. We investigated the impact of COVID-19 restrictions on epidemiological trends of E. coli BSI antimicrobial resistance (AMR) across South West England. METHODS: We undertook a retrospective ecological analysis utilizing routine surveillance data of E. coli BSI cases reported to the UK Health Security Agency between 2016 and 2021. We analysed AMR trends for antimicrobial agents including amoxicillin-clavulanate, ciprofloxacin, piperacillin-tazobactam, gentamicin, third-generation cephalosporins and carbapenems before and after the implementation of COVID-19 restrictions (23 March 2020) using Bayesian segmented regression. RESULTS: We identified 19 055 cases. A total of 50.2% were male. Median age was 76 (interquartile range, 65-85 years). Piperacillin-tazobactam (-2.90% [95% highest density interval {HDI} -4.51%, -0.48%]) and ciprofloxacin (-2.40% [95% HDI -4.35%, 0.48%]) resistance demonstrated immediate step changes at the implementation of COVID-19 restrictions. Gentamicin (odds ratio [OR] 0.92 [95% HDI 0.76, 1.12]) and third-generation cephalosporins (OR 0.95 [95% HDI 0.80, 1.14]) exhibited decreasing annual resistance trends after the implementation of COVID-19 restrictions, with moderate evidence for a lower OR after restrictions as compared to the period before (gentamicin Bayes Factor = 5.10, third-generation cephalosporins Bayes Factor = 6.67). DISCUSSION: COVID-19 restrictions led to abrupt and longer term changes to E.coli BSI AMR. The immediate effects suggest altered transmission, whereas changes to resistant E. coli reservoirs may explain trend effects.

High-content phenotypic screen to identify small molecule enhancers of Parkin-dependent ubiquitination and mitophagy.

Mitochondrial dysfunction and aberrant mitochondrial homeostasis are key aspects of Parkinson's disease (PD) pathophysiology. Mutations in PINK1 and Parkin proteins lead to autosomal recessive PD, suggesting that defective mitochondrial clearance via mitophagy is key in PD etiology. Accelerating the identification and/or removal of dysfunctional mitochondria could therefore provide a disease-modifying approach to treatment. To that end, we performed a high-content phenotypic screen (HCS) of ∼125,000 small molecules to identify compounds that positively modulate mitochondrial accumulation of the PINK1-Parkin-dependent mitophagy initiation marker p-Ser65-Ub in Parkin haploinsufficiency (Parkin +/R275W) human fibroblasts. Following confirmatory counter-screening and orthogonal assays, we selected compounds of interest that enhance mitophagy-related biochemical and functional endpoints in patient-derived fibroblasts. Identification of inhibitors of the ubiquitin-specific peptidase and negative regulator of mitophagy USP30 within our hits further validated our approach. The compounds identified in this work provide a novel starting point for further investigation and optimization.

Use of novel psychoactive substances by inpatients on general adult psychiatric wards.

OBJECTIVES: Non-illicit alternatives to controlled drugs, known as novel psychoactive substances (NPS), have recently risen to prominence. They are readily available, with uncertain pharmacology and no widely available assay. Given that psychiatric patients are at risk of comorbid substance abuse, we hypothesised that NPS use would be present in the psychiatric population, and sought to determine its prevalence and investigate the characteristics of those who use these drugs with a retrospective review of discharge letters. SETTING: General adult inpatient wards of a psychiatric hospital in a Scottish city. PARTICIPANTS: All adult inpatients (18-65) discharged from general psychiatric wards between 1 July 2014 and 31 December 2014. Of the 483 admissions identified, 46 were admissions for maintenance electroconvulsive therapy (ECT) and were excluded. Of the remaining 437 admissions, 49 discharge letters were unobtainable, leaving 388 admissions to analyse. PRIMARY OUTCOME MEASURE: The mention, or lack thereof, of NPS use in discharge letters was our planned primary outcome measure and was also the primary outcome measure we used in our analysis. RESULTS: NPS use was identified in 22.2% of admissions, contributing to psychiatric symptoms in 59.3%. In comparison to non-users, NPS users were younger (p<0.01), male and more likely to have a forensic history ((p<0.001) for both). The diagnosis of drug-induced psychosis was significantly more likely in NPS users (p<0.001, OR 18.7, 95% CI 8.1 to 43.0) and the diagnosis of depression was significantly less likely (p<0.005, OR 0.133, CI 0.031 to 0.558). Use of cannabis was significantly more likely in NPS users (p<0.001, OR 4.2, CI 2.5 to 7.1), as was substitute opiate prescribing (p<0.001, OR 3.7, CI 1.8 to 7.4). CONCLUSIONS: NPS use was prevalent among young, male psychiatric inpatients, in particular those with drug-induced psychosis and often occurred alongside illicit drug use.