Genomic evaluation of phenotypic antibiotic susceptibility patterns as a surrogate for MRSA relatedness and putative transmission during outbreak investigations.

Antibiograms have been used during outbreak investigations for decades as a surrogate for genetic relatedness of Methicillin-resistant (MRSA). In this study, we evaluate the accuracy of antibiograms in detecting transmission, using genomic epidemiology as the reference standard. We analysed epidemiological and genomic data from 1,465 patients and 1,465 MRSA isolates collected at a single clinical microbiology laboratory in the United Kingdom over a one-year period.

The mutational landscape of Staphylococcus aureus during colonisation.

Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution.

Phenotypic and genotypic correlates of the sodium bicarbonate-responsive phenotype among methicillin-resistant Staphylococcus aureus isolates from skin and soft-tissue infections.

Objectives: The objective of this study is to assess the frequency of the novel sodium bicarbonate (NaHCO)-responsive phenotype, wherein clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates are rendered susceptible to standard-of-care β-lactams in the presence of NaHCO, in a collection of 103 clinical U.S. MRSA skin and soft-tissue infection (SSTI) isolates and 22 clinical European SSTI isolates.

Evolution and host-specific adaptation of .

The major human bacterial pathogen causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups.

Evaluating the impact of genomic epidemiology of methicillin-resistant (MRSA) on hospital infection prevention and control decisions.

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019.

Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data.

Background: 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.

The clinical, genomic, and microbiological profile of invasive multi-drug resistant in a major teaching hospital in the United Kingdom.

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.

Dissemination of carbapenemase-producing in Ireland from 2012 to 2017: a retrospective genomic surveillance study.

The spread of carbapenemase-producing (CPE) is of major public health concern. The transmission dynamics of CPE in hospitals, particularly at the national level, are not well understood. Here, we describe a retrospective nationwide genomic surveillance study of CPE in Ireland between 2012 and 2017.

Characteristics of Isolated from Patients in Busia County Referral Hospital, Kenya.

is an important pathogen associated with hospital, community, and livestock-acquired infections, with the ability to develop resistance to antibiotics. Nasal carriage by hospital inpatients is a risk for opportunistic infections. Antibiotic susceptibility patterns, virulence genes and genetic population structure of nasal isolates, from inpatients at Busia County Referral Hospital (BCRH) were analyzed.

Multi-Drug Resistant Carriage in Abattoir Workers in Busia, Kenya.

Abattoir workers have been identified as high-risk for livestock-associated Staphylococcus aureus carriage. This study investigated S. aureus carriage in abattoir workers in Western Kenya.

Large-Scale Evaluation of a Rapid Fully Automated Analysis Platform to Detect and Refute Outbreaks Based on MRSA Genome Comparisons.

Genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) could transform outbreak investigations, but its clinical introduction is hampered by the lack of automated data analysis tools to rapidly and accurately define transmission based on sequence relatedness. We aimed to evaluate a fully automated bioinformatics system for MRSA genome analysis versus a bespoke researcher-led manual informatics pipeline. We analyzed 781 MRSA genomes from 777 consecutive patients identified over a 9-month period in a clinical microbiology laboratory in the United Kingdom.

Significant variability exists in the cytotoxicity of global methicillin-resistant lineages.

is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI).

Defining nosocomial transmission of and antimicrobial resistance genes: a genomic surveillance study.

Background: is a leading cause of bloodstream infections. Developing interventions to reduce infections requires an understanding of the frequency of nosocomial transmission, but the available evidence is scarce. We aimed to detect and characterise transmission of and associated plasmids in a hospital setting.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.

Background: A new variant of SARS-CoV-2, B.1.1.

A common protocol for the simultaneous processing of multiple clinically relevant bacterial species for whole genome sequencing.

Whole-genome sequencing is likely to become increasingly used by local clinical microbiology laboratories, where sequencing volume is low compared with national reference laboratories. Here, we describe a universal protocol for simultaneous DNA extraction and sequencing of numerous different bacterial species, allowing mixed species sequence runs to meet variable laboratory demand. We assembled test panels representing 20 clinically relevant bacterial species.

Definition of a genetic relatedness cutoff to exclude recent transmission of meticillin-resistant : a genomic epidemiology analysis.

Background: Whole-genome sequencing (WGS) can be used in genomic epidemiology investigations to confirm or refute outbreaks of bacterial pathogens, and to support targeted and efficient infection control interventions. We aimed to define a genetic relatedness cutoff, quantified as a number of single-nucleotide polymorphisms (SNP), for meticillin-resistant (MRSA), above which recent (ie, within 6 months) patient-to-patient transmission could be ruled out.

Methods: We did a retrospective genomic and epidemiological analysis of MRSA data from two prospective observational cohort studies in the UK to establish SNP cutoffs for genetic relatedness, above which recent transmission was unlikely.

Quantifying acquisition and transmission of Enterococcus faecium using genomic surveillance.

Nosocomial acquisition and transmission of vancomycin-resistant Enterococcus faecium (VREfm) is the driver for E. faecium carriage in hospitalized patients, which, in turn, is a risk factor for invasive infection in immunocompromised patients. In the present study, we provide a comprehensive picture of E.

Defining metrics for whole-genome sequence analysis of MRSA in clinical practice.

Bacterial sequencing will become increasingly adopted in routine microbiology laboratories. Here, we report the findings of a technical evaluation of almost 800 clinical methicillin-resistant (MRSA) isolates, in which we sought to define key quality metrics to support MRSA sequencing in clinical practice. We evaluated the accuracy of mapping to a generic reference versus clonal complex (CC)-specific mapping, which is more computationally challenging.

Evaluation of a fully automated bioinformatics tool to predict antibiotic resistance from MRSA genomes.

Objectives: The genetic prediction of phenotypic antibiotic resistance based on analysis of WGS data is becoming increasingly feasible, but a major barrier to its introduction into routine use is the lack of fully automated interpretation tools. Here, we report the findings of a large evaluation of the Next Gen Diagnostics (NGD) automated bioinformatics analysis tool to predict the phenotypic resistance of MRSA.

Methods: MRSA-positive patients were identified in a clinical microbiology laboratory in England between January and November 2018.

The Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression.

Gene transfer and homologous recombination in has the potential to trigger the emergence of pandemic lineages, as exemplified by lineages of 1 and 89 that emerged in the 1980s and 2000s, respectively. Although near-identical replacement gene transfer events in the (NADase) and (streptolysin O) loci conferring high expression of these toxins underpinned the success of these lineages, extension to other genotype lineages is unreported. The emergent 89 lineage was characterized by five regions of homologous recombination additional to , including complete loss of the hyaluronic acid capsule synthesis locus , a genetic trait replicated in two other leading types and recapitulated by other types by inactivating mutations.

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study.

Background: Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp.

Pilot Evaluation of a Fully Automated Bioinformatics System for Analysis of Methicillin-Resistant Staphylococcus aureus Genomes and Detection of Outbreaks.

Genomic surveillance that combines bacterial sequencing and epidemiological information will become the gold standard for outbreak detection, but its clinical translation is hampered by the lack of automated interpretation tools. We performed a prospective pilot study to evaluate the analysis of methicillin-resistant (MRSA) genomes using the Next Gen Diagnostics (NGD) automated bioinformatics system. Seventeen unselected MRSA-positive patients were identified in a clinical microbiology laboratory in England over a period of 2 weeks in 2018, and 1 MRSA isolate per case was sequenced on the Illumina MiniSeq instrument.