Sam Lipworth

University of Oxford | OX · Division of Medical Sciences

Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in AMR/virulence). The widespread application of this technique is currently primarily limited...

The incidence of bloodstream infections (BSIs) caused by Enterobacteriaceae (e.g. Escherichia coli, Klebsiella pneumoniae) continues to increase globally and the threat of untreatable disease is significant1. Prophylactic vaccines potentially represent an alternative approach to combating antimicrobial resistance (AMR) by reducing antibiotic usage...

The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however the causes of this are unclear and effective interventions are therefore hard to design. In this study we sequenced 3468 sequential, unselected isolates over a decade in Oxfordshire, UK. We de...

Background Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explai...

Background : Clinical management guidelines (CMGs) can be useful tools to guide clinician’s decision making and enable consistent evidence-based high-quality care. Here, we assessed whether their objective quality has improved over time by considering CMGs for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and fro...

Background: Gram-negative organisms are common causes of bloodstream infection during the neonatal period and early childhood with high morbidity and mortality as well as increasing concern about associated antimicrobial resistance. Whilst several large sequencing studies have permitted detailed analysis of the population structure of these isolate...

Analysing the flanking sequences surrounding genes of interest is often highly relevant to understanding the role of mobile genetic elements (MGEs) in horizontal gene transfer, particular for antimicrobial resistance genes. Here, we present Flanker, a Python package which performs alignment-free clustering of gene flanking sequences in a consistent...

Objective: To assess the responsiveness and quality of clinical management guidelines (CMGs) in SARS, MERS and COVID-19 and determine whether this has improved over time. Design: Rapid literature review, quality assessment and focus group consultation. Data Sources: Google and Google scholar were systematically searched from inception to 6th June 2...

Background The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited. Methods We conducted unselected, population-level genomic surveillanc...

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is curren...

Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is curren...

Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods We did a phase 1/2, single-blind, randomised controlled trial in five t...

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without f...

Objective To appraise the availability, quality, and inclusivity of clinical guidelines produced in the early stage of the coronavirus disease 2019 (covid-19) pandemic. Design Rapid review. Data sources Ovid Medline, Ovid Embase, Ovid Global Health, Scopus, Web of Science Core Collection, and WHO Global Index Medicus, searched from inception to 1...

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without f...

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without f...

Background: Hospital outbreaks of carbapenemase-producing organisms, such as blaIMP-4-containing organisms, are an increasing threat to patient safety. Objectives: To investigate the genomic dynamics of a 10 year (2006-15) outbreak of blaIMP-4-containing organisms in a burns unit in a hospital in Sydney, Australia. Methods: All carbapenem-non-...

Background: The epidemiology of CNS infections in Europe is dynamic, requiring that clinicians have access to up-to-date clinical management guidelines (CMGs) to aid identification of emerging infections and for improving quality and a degree of standardisation in diagnostic and clinical management practices. This paper presents a systematic revie...

In our recent study of 203 sequential isolates evaluating the ability of whole genome sequencing (WGS) to predict clarithromycin resistance in Mycobacterium abscessus ( M. abscessus ) (1), we demonstrated high sensitivity but poor specificity of mutations identified in a literature search. …

Background Numbers of academic medicine trainees have been declining internationally. Many countries have taken differing approaches to improving recruitment, with some having established pathways. In the UK, the academic foundation programme (AFP) is one such pathway aimed towards those interested in an academic medical career. Variation exists am...

The clinical phenotype of zoonotic tuberculosis and its contribution to the global burden of disease are poorly understood and probably underestimated. This shortcoming is partly because of the inability of currently available laboratory and in silico tools to accurately identify all subspecies of the Mycobacterium tuberculosis complex (MTBC). We p...

Mycobacterium abscessus is emerging as an important pathogen in chronic lung diseases, with concern regarding patient-to-patient transmission. The recent introduction of routine whole-genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterize the genetic determinants of resistance....

BACKGROUND The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHO...

Mycobacterium abscessus is emerging as an important pathogen in chronic lung diseases with concern regarding patient to patient transmission. The recent introduction of routine whole genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterise the genetic determinants of resistance. W...

Lipid droplets found in algae and other microscopic organisms have become of interest to many researchers partially because they carry the capacity to produce bio-oil for the mass market. They are of importance in biology and clinical practice because their presence can be a phenotypic marker of an altered metabolism, including reversible resistanc...

The clinical phenotype of zoonotic tuberculosis, its contribution to the global burden of disease and prevalence are poorly understood and probably underestimated. This is partly because currently available laboratory and in silico tools have not been calibrated to accurately identify all subspecies of the Mycobacterium tuberculosis complex ( Mtbc...

Background Arthropod-borne virus (Arbovirus) infections are considered an emerging threat for Europe, with an increase in cases in recent decades. The increase in global travel and trade has contributed to the introduction of vectors and viruses into new geographical areas. Tropical arboviruses such as dengue and chikungunya have re-emerged causing...

⁠Introduction Obesity affects just over a quarter of adults in England (Public Health England, 2016)⁠. There is an urgent need for novel evidence based therapeutic regimes to underpin the emerging field of medical management of obesity. Recent randomised placebo controlled trials have shown the GLP1 agonist liraglutide to be efficacious in a dose d...

Tuberculosis remains a threat to global health and recent attempts to shorten therapy have not succeeded mainly due to cases of clinical relapse. This has focussed attention on the importance of “dormancy” in tuberculosis. There are a number of different definitions of the term and a similar multiplicity of different in vitro and in vivo models. Th...

Introduction It is well established that asthma and obstructive sleep apnoea (OSA) are significantly more prevalent in obese vs. non-obese populations. To date however there is limited data on whether this risk is increased with severity of obesity as most studies classify all patients >30 Kg/m2 simply as ‘obese’. In addition, many existing studies...

We aimed to explore the phenomenon of phenotypic resistance to antimycobacterial antibiotics and to determine whether this was associated with cell age or the presence of lipid bodies. The accumulation of lipid-body-positive [lipid-rich (LR)] cells was followed using cell staining and flow cytometry. LR cells of Mycobacterium smegmatis, Mycobacteri...

Previous studies have focused upon the relationship between airway inflammation and hyperresponsiveness with different conclusions. We re-examined the relationship between airway inflammation (FE(NO)), hyperresponsiveness to methacholine (AHR), and calibre (FEV(1) % predicted) in mild-to-moderate asthmatics. We searched our database for asthmatics...

Tiotropium has been shown to improve lung function, quality of life, and exacerbations and reduce mortality when compared with placebo in COPD. It remains unclear whether benefits are seen when tiotropium is used in conjunction with inhaled corticosteroids (ICSs) plus long-acting β-agonists (LABAs). We performed a retrospective cohort study using a...

To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD. Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidi...

Introduction and Objectives We wished to examine therelationships between inflammation (FENO),methacholine challenge (AHR) and airway calibre (FEV1%) in a group of mild-to-moderate asthmatics. Methods We searched our patient database forthose individuals with a known diagnosis of asthma who had a methacholine PC20≤ 8 mg/ml. Data regarding FEV1%, FE...

Introduction and objectives We wished to examine if β blockers reduced mortality in addition to stepwise therapy for COPD, independent of cardiovascular disease. Methods We searched data provided by the Information Services Division of NHS Scotland, to identify patients in NHS Tayside, who required a hospital admission due to COPD. We then searched...