Nicole Stoesser

University of Oxford | OX · Nuffield Department of Clinical Medicine

The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common infections. blaKPC, encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10 kb). Here we charac...

Background Weekend hospital admission is associated with increased mortality, but the contributions of varying illness severity and admission time to this weekend effect remain unexplored. Methods We analysed unselected emergency admissions to four Oxford University National Health Service hospitals in the UK from Jan 1, 2006, to Dec 31, 2014. The...

Plasmids are extra-chromosomal genetic elements ubiquitous in bacteria, and commonly transmissible between host cells. Their genomes include variable repertoires of ‘accessory genes,’ such as antibiotic resistance genes, as well as ‘backbone’ loci which are largely conserved within plasmid families, and often involved in key plasmid-specific functi...

Background: The control of Clostridium difficile infections is an international clinical challenge. The incidence of C difficile in England declined by roughly 80% after 2006, following the implementation of national control policies; we tested two hypotheses to investigate their role in this decline. First, if C difficile infection declines in En...

Unlabelled: Escherichia colisequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and o...

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 achieve...

The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current culture-based turnaround times for bacterial identification in clinical samples and antimicrobial susceptibility testing (AST) are typically 18–24 h. We present a novel proof-of-concept me...

Background Syndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses. Methods We estimated positivity and incidence of SARS-CoV-2, influenza A/B, and R...

Structured summary Background Hospital sinks are environmental reservoirs that harbour healthcare-associated (HCA) pathogens. Selective pressures in sink environments, such as antibiotic residues, nutrient waste and hardness ions, may promote antibiotic resistance gene (ARG) exchange between bacteria. However, cheap and accurate sampling methods to...

Respiratory viral infections are a major global clinical problem, and rapid, cheap, scalable and agnostic diagnostic tests that capture genome-level information on viral variation are urgently needed. Metagenomic approaches would be ideal, but remain currently limited in that much of the genetic content in respiratory samples is human, and amplifyi...

We demonstrate the rapid capture, enrichment, and identification of bacterial pathogens using Adaptive Channel Bacterial Capture (ACBC) devices. Using controlled tuning of device backpressure in polydimethylsiloxane (PDMS) devices, we enable the controlled formation of capture regions capable of trapping bacteria from low cell density samples with...

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited, especially after widespread national testing stopped. We studied 245,895 adult...

Background: An outbreak of severe acute hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 has subsequently been linked to infections by adenovirus-associated virus 2 (AAV2) and other 'helper viruses', including human adenovirus (HAdV). Aim: We investigated clinical characteristics and temporal distribution of acute hepatitis with u...

Following primary SARS-CoV-2 vaccination, whether boosters or breakthrough infections provide greater protection against SARS-CoV-2 infection is incompletely understood. Here we investigated SARS-CoV-2 antibody correlates of protection against new Omicron BA.4/5 (re-)infections and anti-spike IgG antibody trajectories after a third/booster vaccinat...

Wastewater-based epidemiology (WBE) for population-level surveillance of antimicrobial resistance (AMR) is gaining significant traction, but the impact of wastewater sampling methods on results is unclear. In this study, we characterized taxonomic and resistome differences between single-timepoint-grab and 24 h composites of wastewater influent fro...

Whole genome sequencing (WGS) of healthcare-associated pathogens is recognised as the gold standard for isolate typing and the recognition of transmission networks and outbreaks. However, it remains reasonably expensive to process small numbers of isolates in real-time, and frequently requires specific expertise to enable both sequencing and the an...

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. It is accepted that MCR-1 affects bacterial fitness, and this fitness cost correlates with bacterial membrane lipid A perturbation. However, the detailed molecular mechanism remains unclear. Here, we screened out a novel MCR-1 variant...

Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, the extent of plasmid sharing and evolution between Enterobacterales causing human infections and other niches remains unclear, including the emergence of resistance plasmids. Dense, unsele...

Background The COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy.

Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person’s...

Background Antimicrobial resistance (AMR) in E. coli is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to a variants in a curated reference database with an implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In th...

Introduction: There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time. Methods: A popul...

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we use spatio-temp...

Plasmids are major vectors of bacterial antibiotic resistance, but understanding of factors associated with plasmid antibiotic resistance gene (ARG) carriage is limited. We curated > 14,000 publicly available plasmid genomes and associated metadata. Duplicate and replicate plasmids were excluded; where possible, sample metadata was validated extern...

Complete, accurate, cost-effective, and high-throughput reconstruction of bacterial genomes for large-scale genomic epidemiological studies is currently only possible with hybrid assembly, combining long- (typically using nanopore sequencing) and short-read (Illumina) datasets. Being able to use nanopore-only data would be a significant advance. Ox...

The increasing frequency and magnitude of viral outbreaks in recent decades, epitomized by the COVID-19 pandemic, has resulted in an urgent need for rapid and sensitive diagnostic methods. Here, we present a methodology for virus detection and identification that uses a convolutional neural network to distinguish between microscopy images of fluore...

Plasmids are one of the main vectors of bacterial antibiotic resistance, but understanding of risk factors associated with plasmid antibiotic resistance gene (ARG) carriage is limited. We curated > 14000 publicly available plasmid genomes and associated metadata. Duplicate and replicate plasmids were excluded; where possible, sample metadata was va...

The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current gold-standard antimicrobial susceptibility tests (ASTs) are low-throughput and can take up to 48 hours, with implications for patient care. We present advances towards a novel, rapid AST,...

Background: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in differ...

Background: Monitoring infection trends is vital to informing public health strategy. Detecting and quantifying changes in growth rates can inform policymakers' rationale for implementing or continuing interventions aimed at reducing impact. Substantial changes in SARS-CoV-2 prevalence with emergence of variants provides opportunity to investigate...

Background: Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy. Methods: We investigated adult inpatients with Escherichia coli bacteraemia at Oxf...

Background Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vi...

Background Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population. Methods We perform an epidemiolog...

Background: The SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses. Methods: In a natio...

Plasmids are key vectors of bacterial antibiotic resistance, but understanding of risk factors associated with plasmid antibiotic resistance gene (ARG) carriage is limited. We curated >14000 publicly available plasmid genomes and associated metadata. Duplicate and replicate plasmids were excluded; where possible, sample metadata was validated exter...

Wastewater-based epidemiology (WBE) for population-level surveillance of antimicrobial resistance (AMR) is gaining significant traction, but the impact of wastewater sampling methods on results is unclear. In this study we characterised taxonomic and resistome differences between single-timepoint-grab and 24H-composites of wastewater influent from...

Background Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy. Methods We investigated adult inpatients with Escherichia coli bacteraemia at Oxfo...

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi...

Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out in many settings, there is a need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity. We evaluate whether a single vaccination in individuals who have already been infected with SARS-CoV-2 generates similar initial and...

Background Shotgun metagenomic sequencing is increasingly popular in taxonomic and resistome-profiling of polymicrobial samples due to its agnostic nature and data versatility. However, caveats include high- cost, sequencing depth/sensitivity trade-offs, and challenging bioinformatic deconvolution. Targeted PCR-based profiling optimises sensitivity...

Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, the extent of plasmid sharing and evolution between Enterobacterales causing human infections and other niches remains unclear, including the emergence of resistance plasmids. Dense, unsele...

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 o...

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 o...

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-sp...

Complete, accurate, cost-effective, and high-throughput reconstruction of bacterial genomes for large-scale genomic epidemiological studies is currently only possible with hybrid assembly, combining long- (typically using nanopore sequencing) and short-read (Illumina) datasets. Being able to utilise nanopore-only data would be a significant advance...

Plasmids carry genes conferring antimicrobial resistance (AMR), and other clinically important traits; their ability to move within and between species may provide the machinery for rapid dissemination of such genes. Despite this, existing studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or...

Objectives We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) evidence of concordance between wastewater-human AMR prevalence estimates, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordan...

A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous bla OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399...

Background The COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy. Methods To develop a real-time screening process, we included results fro...

Background Reported bacteraemia outcomes following inactive empirical antibiotics (as judged by in vitro testing) are conflicting, potentially reflecting heterogeneous effects of species, minimum inhibitory concentration (MIC) breakpoints defining resistance/susceptibility, and times to rescue therapy. Methods We investigated adult inpatients with...

Background The SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses. Methods In a nationall...

SARS-CoV-2 virtual wards have successfully developed to monitor and escalate patients to hospital throughout the pandemic. Here we describe the case of an 84 year old man who received his complete care for severe SARS-CoV-2 pneumonitis at home, including the administration of oxygen, dexamethasone and tocilizumab.

Genome sequencing is pivotal to SARS-CoV-2 surveillance, elucidating the emergence and global dissemination of acquired genetic mutations. Amplicon sequencing has proven very effective for sequencing SARS-CoV-2, but prevalent mutations disrupting primer binding sites have necessitated the revision of sequencing protocols in order to maintain perfor...

Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody respon...

Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 11...

The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly sel...

Background Healthcare-associated wastewater reservoirs and asymptomatic gastrointestinal patient colonisation by carbapenemase-producing Enterobacterales (CPE) can be important in nosocomial CPE dissemination and infection. We characterised these niches and within-niche diversity in a blaKPC-associated CPE (KPC-E) endemic healthcare setting, to bet...

Background ‘Classic’ symptoms (cough, fever, loss of taste/smell) prompt SARS-CoV-2 PCR-testing in the UK. Studies have assessed the ability of different symptoms to identify infection, but few have compared symptoms over time (reflecting variants) and by vaccination status. Methods Using the COVID-19 Infection Survey, sampling households across t...

BACKGROUND: “Classic” symptoms (cough, fever, loss of taste/smell) prompt severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing in the United Kingdom. Studies have assessed the ability of different symptoms to identify infection, but few have compared symptoms over time (reflecting variants) and by vac...

Several bioinformatics genotyping algorithms are now commonly used to characterise 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, particularl...

Objectives To inform point-of-care test (POCT) development, we quantified the primary care demand for laboratory microbiology tests by describing their frequencies overall, frequencies of positives, most common organisms identified, temporal trends in testing and patterns of cotesting on the same and subsequent dates. Design Retrospective cohort s...

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 Unit...

Objective To describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK. Methods Data on paediatric Emergency Department (ED) attendances (0-15 years inclusive), respiratory virus testing, vital signs and mortality at Oxford University Hospitals were summarised using descriptiv...

Enterobacterales from livestock are potentially important reservoirs for antimicrobial resistance (AMR) to pass through the food chain to humans, thereby increasing the AMR burden and affecting our ability to tackle infections. In this study 168 isolates from four genera of the order Enterobacterales , primarily Escherichia coli , were purified fro...