Suchergebnisse

BACKGROUND: Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely 'undetectable' transmission remains the ultimate aim. METHODS: WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically-related cluster of E-MRSA15 isolated from patients registered to the same General Practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases and determine potential for on-going transmission. RESULTS: We identified 15 MRSA-positive individuals with 27 highly-related MRSA isolates who were linked to the GP surgery, two of whom died with MRSA bacteremia. Of the 13 cases who were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an on-going source of infection. CONCLUSIONS: Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings. ; This work was supported by grants from the UK Clinical Research Collaboration Translational Infection Research Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by a Healthcare Infection Society Major Research Grant (to Prof. Peacock), and by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute. MST was a Wellcome Trust Clinical PhD Fellow. FC was supported by the Wellcome Trust (201344/Z/16/Z). These sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The public health investigation was supported by Public Health England.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an emerging problem in many parts of the world. LA-MRSA has been isolated previously from animals and humans in the United Kingdom (UK), but the prevalence is unknown. The aim of this study was to determine the prevalence and to describe the molecular epidemiology of LA-MRSA isolated in the East of England (broadly Cambridge and the surrounding area). We accessed whole genome sequence data for 2,283 MRSA isolates from 1,465 people identified during a 12-month prospective study between 2012 and 2013 conducted in the East of England, United Kingdom. This laboratory serves four hospitals and 75 general practices. We screened the collection for multilocus sequence types (STs) and for host specific resistance and virulence factors previously associated with LA-MRSA. We identified 13 putative LA-MRSA isolates from 12 individuals, giving an estimated prevalence of 0.82% (95% CI 0.47% to 1.43%). Twelve isolates were mecC-MRSA (ten CC130, one ST425 and one ST1943) and single isolate was ST398. Our data demonstrate a low burden of LA-MRSA in the East of England, but the detection of mecC-MRSA and ST398 indicates the need for vigilance. Genomic surveillance provides a mechanism to detect and track the emergence and spread of MRSA clones of human importance. ; Supported by grants from the UKCRC Translational Infection Research (TIR) Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Ofce of the Scottish Government Health Directorate (to Prof. Peacock); a Hospital Infection Society Major Research Grant, and by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute. Tis work was supported by the Wellcome Trust 201344/Z/16/Z. M.E.T. is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation, and by the NIHR Cambridge Biomedical Research Centre.

Background: Horizontal transfer of mobile genetic elements (MGEs) that carry virulence and antimicrobial resistance genes mediates the evolution of methicillin-resistant Staphylococcus aureus, and the emergence of new MRSA clones. Most MRSA lineages show an association with specific MGEs and the evolution of MGE composition following clonal expansion has not been widely studied. Results: We investigated the genomes of 1193 S. aureus bloodstream isolates, 1169 of which were MRSA, collected in the UK and the Republic of Ireland between 2001 and 2010. The majority of isolates belonged to clonal complex (CC)22 (n=923), which contained diverse MGEs including elements that were found in other MRSA lineages. Several MGEs showed variable distribution across the CC22 phylogeny, including two antimicrobial resistance plasmids (pWBG751-like and SAP078A-like, carrying erythromycin and heavy metal resistance genes, respectively), a pathogenicity island carrying the enterotoxin C gene and two phage types Sa1int and Sa6int. Multiple gains and losses of these five MGEs were identified in the CC22 phylogeny using ancestral state reconstruction. Analysis of the temporal distribution of the five MGEs between 2001 and 2010 revealed an unexpected reduction in prevalence of the two plasmids and the pathogenicity island, and an increase in the two phage types. This occurred across the lineage and was not correlated with changes in the relative prevalence of CC22, or of any sub-lineages within in. Conclusions: Ancestral state reconstruction coupled with temporal trend analysis demonstrated that epidemic MRSA CC22 has an evolving MGE composition, and indicates that this important MRSA lineage has continued to adapt to changing selective pressure since its emergence. ; The study was funded by grants from the UKCRC Translational Infection Research Initiative, and the Medical Research Council (grant no. G1000803) with contributions to the grant from the Biotechnology and Biological Sciences Research Council (BBSRC), the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to SJP). DJ, SRH and JP are funded by the Wellcome Trust grant 098051. FC is funded by the Wellcome Trust grant 201,344/Z/16/Z. AEM is funded by BBSRC grant BB/M014088/1. MET is a Clinician Scientist Fellow funded by the Academy of Medical Sciences and The Health Foundation and supported by the NIHR Cambridge Biomedical Research Centre. In all cases the funders were not involved in any aspect of the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

We demonstrated that some non-synonymous and synonymous mutations in $\textit{gyrA}$ in $\textit{Mycobacterium tuberculosis}$ result in systematic false-resistance results to fluoroquinolones using the Hain GenoType MTBDRsl assays (version 1 and 2) by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes, designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings. ; T.M.W. is a University of Oxford National Institute for Health Research (NIHR) academic clinical lecturer. N.A. was supported by a doctoral study fund from Colciencias. T.S. was supported by grants from the Swedish Heart and Lung Foundation and the Marianne and Marcus Wallenberg Foundation. F.C. was supported by the Wellcome Trust (grant 201344/Z/16/Z). D.W.C. and T.E.A.P. are NIHR senior investigators supported by the NIHR Oxford Biomedical Research Centre, NIHR Oxford Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance (grant HPRU-2012-10041), and the Health Innovation Challenge Fund (grant T5-358). S.N. was supported by grants from the German Center for Infection Research (DZIF), the European Union TB-PAN-NET (grant FP7-223681), and PathoNgenTrace (grant 278864). S.J.P. was supported by the Health Innovation Challenge Fund (grants HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust. C.U.K. is a junior research fellow at Wolfson College, Cambridge.