Presentations & Publications


2020

Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae

 

In many clinically important bacteria, antibiotic resistance genes are primarily carried on plasmids. These can spread horizontally between different strains and species. However, current surveillance systems track chromosomal lineages of bacteria only, leading to an incomplete understanding of how resistance spreads, from within an individual hospital to across country borders. We present an integrated, high-resolution analysis of both chromosome and plasmid sequences using Klebsiella pneumoniae isolates sampled during a European survey. We show that carbapenemase genes, which confer resistance to last-line antibiotics, have spread in diverse ways including via one plasmid/multiple lineages (blaOXA-48-like), multiple plasmids/multiple lineages (blaVIM, blaNDM), and multiple plasmids/one lineage (blaKPC). These different trajectories must be considered in genomic surveillance systems and the design of new interventions.

 

This publication is a follow-up study to the Europe-wide study that describes the transmission dynamics of carbapenem-resistant Klebsiella pneumoniae isolates. In the first publication (2019), the researchers analysed the genomes of almost 2,000 K. pneumoniae samples taken from the European Survey on Carbapenamase-Producing Enterobacteriaceae (EuSCAPE). In the 2020 publication, the researchers studied the modes of dissemination used by carbapenemase genes, using a combination of long- and short-read sequence data. The results revealed the diverse trajectories of antibiotic resistance genes in clinical settings, either using one plasmid/multiple lineages, or multiple plasmids/multiple lineages, or multiple plasmids/one lineage.

 

This study was originally funded by the European Centres for Disease Prevention and Control (ECDC) and carried out in collaboration with the ESCMID Study Group on Molecular Epidemiologic Markers (ESGEM), the Centre for Genomic Pathogen Surveillance, based at the Wellcome Sanger Institute (UK) and the University of Freiburg, Germany.

2019

A Europe-wide study that describes the transmission dynamics of carbapenem-resistant Klebsiella pneumoniae isolates was carried out in collaboration with the ESCMID Study Group on Molecular Epidemiologic Markers (ESGEM), the Centre for Genomic Pathogen Surveillance, based at the Wellcome Sanger Institute and the University of Freiburg, Germany. Researchers analysed the genomes of almost 2,000 K. pneumoniae samples taken from the European Survey on Carbapenamase-Producing Enterobacteriaceae (EuSCAPE) originally funded by the European Centres for Disease Prevention and Control (ECDC). Clinical isolates were from patients in 244 hospitals in 32 countries. The results, published in Nature Microbiology, will inform public health efforts to control the spread of these infections in hospitals at national levels. The survey is the largest of its kind and is the first step towards  standardised surveillance of carbapenem-resistant bacteria on a pan-European scale. Resistance against carbapenems (CR) is far more frequent in K. pneumoniae than in other Enterobacteriaceae, and outnumbers CR-Escherichia coli 11:1. It is currently also the fastest growing resistance problem in Europe and since carbapenems are regarded as a ‘last-line’ antibiotic reserved for the treatment of multidrug-resistant strains, carbapenem-resistant isolates are often classified as extremely drug resistant (XDR).
Resistant isolates showed a remarkably constrained genetic diversity whereby 70% of CR-K. pneumoniae were concentrated in only four clonal lineages, all of them bearing the hallmarks of so called ‘high risk’ clones. Moreover, there was a strong correlation between genetic and geographic distance with 52% of the genetically nearest neighbours co-circulating among patients treated in the same hospital. Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread between patients correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility. The authors conclude (i) that the epidemic of carbapenem-resistant K. pneumoniae is driven by a nosocomial expansion of few hospital adapted clones, (ii) that antibiotic use is the most important effect modifier, and (iii) that OneHealth reservoirs are not likely to explain the observed pattern.    

2016

Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe

5 May 2016 mBio vol. 7 no. 3 e00444-16; doi: 10.1128/mBio.00444-16

 

In this ESGEM paper, we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) community-oriented database infrastructure and analysis tools.