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.
View Article and Find Full Text PDFEnteric fever remains a major public health problem in South and Southeast Asia. The recent roll-out of the typhoid conjugate vaccine protecting against S. Typhi exhibits great promise for disease reduction in high burden areas.
View Article and Find Full Text PDFBackground: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes.
Methods: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium.
is a ubiquitous component of the human gut microbiome, but is also a common pathogen, causing around 40, 000 bloodstream infections (BSI) in the United Kingdom (UK) annually. The number of BSI has increased over the last decade in the UK, and emerging antimicrobial resistance (AMR) profiles threaten treatment options. Here, we combined clinical, epidemiological, and whole genome sequencing data with high content imaging to characterise over 300 isolates associated with BSI in a large teaching hospital in the East of England.
View Article and Find Full Text PDFHealthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (=165).
View Article and Find Full Text PDFBackground: Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing.
View Article and Find Full Text PDFHuman adenovirus F41 causes acute gastroenteritis in children, and has recently been associated with an apparent increase in paediatric hepatitis of unknown aetiology in the UK, with further cases reported in multiple countries. Relatively little is known about the genetic diversity of adenovirus F41 in UK children; and it is unclear what, if any, impact the COVID-19 pandemic has had on viral diversity in the UK. Methods that allow F41 to be sequenced from clinical samples without the need for viral culture are required to provide the genomic data to address these questions.
View Article and Find Full Text PDFPurpose: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials.
View Article and Find Full Text PDFBackground: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam.
Methods: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018.
Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available.
View Article and Find Full Text PDFIntroduction: Lower respiratory tract infection (LRTI) is the most commonly treated infection in critically ill children. Pathogens are infrequently identified on routine respiratory culture, and this is a time-consuming process. A syndromic approach to rapid molecular testing that includes a wide range of bacterial and fungal targets has the potential to aid clinical decision making and reduce unnecessary broad spectrum antimicrobial prescribing.
View Article and Find Full Text PDFSARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs.
View Article and Find Full Text PDFBackground: Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).
Objectives: To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.
Background: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.
Methods: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h.