Dataset Information

Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.

ABSTRACT: The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.

SUBMITTER: Reuter S

PROVIDER: S-EPMC4728378 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.

Reuter Sandra S Török M Estée ME Holden Matthew T G MT Reynolds Rosy R Raven Kathy E KE Blane Beth B Donker Tjibbe T Bentley Stephen D SD Aanensen David M DM Grundmann Hajo H Feil Edward J EJ Spratt Brian G BG Parkhill Julian J Peacock Sharon J SJ

Genome research 20151215 2

The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobia ...[more]

PMID: 26672018

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Project description:IntroductionThe identification of genomic "targets" through next-generation sequencing (NGS) of patient's NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing.MethodsInstitutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James's Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0).ResultsIn total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26-94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was KRAS (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: MET exon 14 skipping (n = 53, 2.6%), MET amplification (n = 26, 1.3%), EGFR (n = 181, 8.8%), HER2 (n = 35, 1.7%), and BRAF (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including ALK (n = 44, 58%), RET (n = 11, 14.5%), ROS1 (n = 16, 21%), and FGFR3 (n = 5, 6.6%), whereas no NTRK fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was KRAS/PIK3CA (n = 19, 17%), EGFR/PIK3CA (n = 10, 8.5%), and KRAS/IDH1 (n = 9, 8%). Other co-alterations of interest identified included KRAS G12A/ROS1 fusion (n = 1) and KRAS G12C/BRAF G469A (n = 2).ConclusionsThis is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK, ROS1, and RET fusions, compared with similar data sets.

Project description:The coronavirus pandemic has necessitated extraordinary human resilience in order to preserve and prolong life and social order. Risks to health and even life are being confronted by workers in health and social care, as well as those in roles previously never defined as "frontline," such as individuals working in community supply chain sectors. The strategy adopted by the United Kingdom (UK) government in facing the challenges of the pandemic was markedly different from other countries. The present study set out to examine what variables were associated with resilience, burnout, and wellbeing in all sectors of frontline workers, and whether or not these differed between the UK and Republic of Ireland (RoI). Individuals were eligible if they were a frontline worker (in health and social care, community supply chain, or other emergency services) in the UK or RoI during the pandemic. Part of a larger, longitudinal study, the participants completed an online survey to assess various aspects of their daily and working lives, along with their attitudes toward their government's handling of the crisis, and measurement of psychological variables associated with heroism (altruism, meaning in life, and resilient coping). A total of 1,305 participants (N = 869, 66.6% from the UK) provided sufficient data for analysis. UK-based workers reported lower wellbeing than the RoI-based participants. In multivariate models, both psychological and pandemic-related variables were associated with levels of resilience, burnout, and wellbeing in these workers, but which pandemic-related variables were associated with outcomes differed depending on the country. The judgment of lower timeliness in their government's response to the pandemic appeared to be a key driver of each outcome for the UK-based frontline workers. These findings provide initial evidence that the different strategies adopted by each country may be associated with the overall wellbeing of frontline workers, with higher detriment observed in the UK. The judgment of the relatively slow response of the UK government to instigate their pandemic measures appears to be associated with lower resilience, higher burnout, and lower wellbeing in frontline workers in the UK.

Project description:Klebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones of K. pneumoniae have been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDR K. pneumoniae at the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDR K. pneumoniae isolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequenced K. pneumoniae populations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of K. pneumoniae and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDR K. pneumoniae isolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulating K. pneumoniae population.IMPORTANCEKlebsiella pneumoniae is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of K. pneumoniae infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant K. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistant K. pneumoniae in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment.

Dataset Information

Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.

Publications

Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.

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