An Electronic Health Record-Wide Association Study to identify populations at increased risk of E. coli bloodstream infections.

Objectives: Escherichia coli bacteraemias have been under mandatory surveillance in the UK for fifteen years, but cases continue to rise. Systematic searches of all features present within electronic healthcare records (EHRs), described here as an EHR-wide association study (EHR-WAS), could potentially identify under-appreciated factors that could be targeted to reduce infections.

Methods: We used data from Oxfordshire, UK, and an EHR-WAS method developed for use with large-scale COVID-19 data to estimate associations between E.

The impact of inter-infection time on antimicrobial resistance profiles in women with multiple urinary tract infections over time.

Background: Urinary tract infection (UTI) treatment in primary care is increasingly complicated by antimicrobial resistance (AMR), and antimicrobial susceptibility profiles are rarely available to prescribers at the point of prescription. Susceptibility profiles from previous urine culture results could inform prescribing, but little is known about associations between previous and current susceptibilities and the impact of time between infections (inter-infection time) on these associations.

Methods: We analysed routinely collected healthcare records of women ≥16 years in Oxfordshire, UK, who had two or more culture-positive urine specimens consistent with a UTI between 2013 and 2019.

Ribosome phenotypes for rapid classification of antibiotic-susceptible and resistant strains of Escherichia coli.

Rapid antibiotic susceptibility tests (ASTs) are an increasingly important part of clinical care as antimicrobial resistance (AMR) becomes more common in bacterial infections. Here, we use the spatial distribution of fluorescently labelled ribosomes to detect intracellular changes associated with antibiotic susceptibility in E. coli cells using a convolutional neural network (CNN).

Developing a framework for tracking antimicrobial resistance gene movement in a persistent environmental reservoir.

Mobile genetic elements are key to the global emergence of antibiotic resistance. We successfully reconstructed the complete bacterial genome and plasmid assemblies of isolates sharing the same carbapenemase gene to understand evolution over time in six confined hospital drains over five years. From 82 isolates we identified 14 unique strains from 10 species with 113 carrying plasmids across 16 distinct replicon types.

Diversity, functional classification and genotyping of SHV β-lactamases in .

Interpreting the phenotypes of alleles in genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal alleles or additional plasmid-borne alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood.

Exploring uncatalogued genetic variation in antimicrobial resistance gene families in Escherichia coli: an observational analysis.

Background: Antimicrobial resistance (AMR) in Escherichia coli is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to variants in a curated reference database, with the implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study, we evaluated the performance of the AMRFinder tool and, subsequently, the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility phenotype predictions in E coli.

Infection Inspection: using the power of citizen science for image-based prediction of antibiotic resistance in Escherichia coli treated with ciprofloxacin.

Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its threat. This study uses citizen science and image feature analysis to profile the cellular features associated with antibiotic resistance in Escherichia coli. Between February and April 2023, we conducted the Infection Inspection project, in which 5273 volunteers made 1,045,199 classifications of single-cell images from five E.

Dissemination and persistence of antimicrobial resistance (AMR) along the wastewater-river continuum.

Antimicrobial resistance (AMR) is a global health hazard. Although clinical and agricultural environments are well-established contributors to the evolution and dissemination of AMR, research on wastewater treatment works (WwTWs) has highlighted their potential role as disseminators of AMR in freshwater environments. Using metagenomic sequencing and analysis, we investigated the changes in resistomes and associated mobile genetic elements within untreated wastewater influents and treated effluents of five WwTWs, and sediments collected from corresponding river environments in Oxfordshire, UK, across three seasonal periods within a year.

Retrospective analysis of hospital electronic health records reveals unseen cases of acute hepatitis with unknown aetiology in adults in Oxfordshire.

Background: An outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other 'helper viruses', including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).

Methods: We used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016-2022, for all ages from 18 months and older.

Detecting changes in population trends in infection surveillance using community SARS-CoV-2 prevalence as an exemplar.

Detecting and quantifying changes in the growth rates of infectious diseases is vital to informing public health strategy and can inform policymakers' rationale for implementing or continuing interventions aimed at reducing their impact. Substantial changes in SARS-CoV-2 prevalence with the emergence of variants have provided an opportunity to investigate different methods for doing this. We collected polymerase chain reaction (PCR) results from all participants in the United Kingdom's COVID-19 Infection Survey between August 1, 2020, and June 30, 2022.

Evaluation of the accuracy of bacterial genome reconstruction with Oxford Nanopore R10.4.1 long-read-only sequencing.

Whole-genome reconstruction of bacterial pathogens has become an important tool for tracking transmission and antimicrobial resistance gene spread, but highly accurate and complete assemblies have largely only historically been achievable using hybrid long- and short-read sequencing. We previously found the Oxford Nanopore Technologies (ONT) R10.4/kit12 flowcell/chemistry produced improved assemblies over the R9.

Nanopore sequencing of influenza A and B in Oxfordshire and the United Kingdom, 2022-23.

Objectives: We evaluated Nanopore sequencing for influenza surveillance.

Methods: Influenza A and B PCR-positive samples from hospital patients in Oxfordshire, UK, and a UK-wide population survey from winter 2022-23 underwent Nanopore sequencing following targeted rt-PCR amplification.

Results: From 941 infections, successful sequencing was achieved in 292/388 (75 %) available Oxfordshire samples: 231 (79 %) A/H3N2, 53 (18 %) A/H1N1, and 8 (3 %) B/Victoria and in 53/113 (47 %) UK-wide samples.

The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.

Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK.

Epidemiology and microbiology of recurrent UTI in women in the community in Oxfordshire, UK.

Background: Recurrent urinary tract infection (rUTI) contributes to significant morbidity and antibiotic usage.

Objectives: To characterize the age of women experiencing rUTI, the microbiology of rUTIs, and the risk of further rUTIs in Oxfordshire, UK.

Patients And Methods: We retrospectively analysed de-identified linked microbiology and hospital admissions data (Infections in Oxfordshire Research Database), between 2008 and 2019, including positive urine cultures from women aged ≥16 years in community settings.

Discordance between different bioinformatic methods for identifying resistance genes from short-read genomic data, with a focus on .

Several bioinformatics genotyping algorithms are now commonly used to characterize antimicrobial resistance (AMR) gene profiles in whole-genome sequencing (WGS) data, with a view to understanding AMR epidemiology and developing resistance prediction workflows using WGS in clinical settings. Accurately evaluating AMR in Enterobacterales, particularly , is of major importance, because this is a common pathogen. However, robust comparisons of different genotyping approaches on relevant simulated and large real-life WGS datasets are lacking.

A new variant of the colistin resistance gene MCR-1 with co-resistance to β-lactam antibiotics reveals a potential novel antimicrobial peptide.

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear.

Model-based evaluation of admission screening strategies for the detection and control of carbapenemase-producing Enterobacterales in the English hospital setting.

Background: Globally, detections of carbapenemase-producing Enterobacterales (CPE) colonisations and infections are increasing. The spread of these highly resistant bacteria poses a serious threat to public health. However, understanding of CPE transmission and evidence on effectiveness of control measures is severely lacking.