Mobile genetic elements; Transmission; Whole genome sequencing; One health; ESBL-producing Enterobacteriaceae
Aguilar-Bultet Lisandra, Bagutti Claudia, Egli Adrian, Alt Monica, Maurer Pekerman Laura, Schindler Ruth, Furger Reto, Eichenberger Lucas, Roloff Tim, Steffen Ingrid, Huebner Philipp, Stadler Tanja, Tschudin-Sutter Sarah (2020), Identification of a cluster of Extended-Spectrum Beta-Lactamase producing Klebsiella pneumoniae sequence type 101 isolated from food and humans, in Clinical Infectious Diseases
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Stadler Tanja, Meinel Dominik, Aguilar-Bultet Lisandra, Huisman Jana, Schindler Ruth, Egli Adrian, Seth-Smith Helena, Eichenberger Lucas, Brodmann Peter, Hübner Philipp, Bagutti Claudia, Tschudin-Sutter Sarah (2018), Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements-identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland., in BMJ Open
Over the last decade, the world has witnessed a dramatic rise of multidrug-resistant gram-negative bacteria. This trend is reflected by a significant increase of resistance to third-generation cephalosporins in Klebsiella pneumoniae and Escherichia coli over the last years at EU level, the most important underlying resistance mechanism being the production of extended-spectrum beta-lactamases (ESBLs). In Switzerland, third-generation cephalosporin resistance in K. pneumonia and E. coli increased concomitantly from less than 2% in 2004 to 11% in 2013. ESBL-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-E. coli was increasingly described as an important cause of community-acquired urinary tract infections worldwide, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Possible community-sources may include foodstuffs and colonization resulting from global travel. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different species of Enterobacteriaceae. The respective contribution of horizontal gene transfer and exchange of plasmids carrying ESBL genes between Enterobacteriaceae to the rapidly expanding epidemiology of ESBL-producers, however, remains elusive.In contrast to conventional typing techniques, such as pulsed-field gel electrophoresis or multilocus sequence typing, whole genome sequencing allows the identification of single-nucleotide polymorphisms that differentiate bacterial strains and mobile genetic elements, such as plasmids at the highest possible resolution, therefore enabling investigation of their relatedness by phylogenetic analyses and ultimately detailed exploration of transmission pathways. This technique has currently been established at our microbiology laboratory and has to date not been applied to determine transmission of both strains and plasmids in a large epidemiological study including clinically relevant ESBL-Enterobacteriaceae-strains, as well as strains recovered from community settings. At our institution, all ESBL-producing Enterobacteriaceae recovered from any specimens obtained by routine clinical practice in both in and outpatient settings have been collected and stored since 2003, representing a unique collection of clinically relevant strains over time.The aim of this research project is to quantity the specific proportion of hospital-wide transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial species and the mobile genetic elements, and to determine if hospital-acquired infections caused by ESBL-producers are related to strains and mobile genetic elements predominantly circulating in the community or in the healthcare setting. This distinction is critical in prevention since the former emphasizes the urgent need to establish or reinforce antibiotic stewardship programs, and the latter would call for more rigorous infection control. The specific aims of this research project include:i) To quantify the extent of hospital-wide transmission of ESBL-producing Enterobacteriaceae by assessing the genetic relatedness of ESBL-producing Enterobacteriaceae among patients and over time.ii) To estimate the contribution of horizontal gene transfer to the spread of ESBL-producing Enterobacteriaceae in both hospital-and community settingsiii) To determine migration of ESBL-producing Enterobacteriaceae between humans and their environment (i.e. foodstuff and wastewater samples) by comparing genetic relatedness of strains recovered from patients and the environment, in the sense of a “one-health”-approach.