Living together in a world of extended-spectrum cephalosporin resistance: molecular snapshots of a complex epidemiology

Extended-spectrum cephalosporinase (ESCase)-producing Enterobacteriaceae from human and animal origin have emerged worldwide during the last decades. Although studies documenting direct transmission between humans and animals are rare, the existence of shared reservoirs of extended-spectrum cephalosporinase genes, plasmids and/or STs suggests cross-transmissions and raises the concern of a possible zoonotic source of ESBL/AmpC-producers for humans. The aim of this thesis is to explore the molecular relatedness of extended-spectrum cephalosporin (ESC)-resistant Enterobacteriaceae of human and animal origin and assess their cross-transmission and epidemiology from a “One health” perspective. Chapter 1, as an introduction provides the necessary background information of the extended-spectrum cephalosporinase-producing Enterobacteriaceae and their complex epidemiology, to offer a better understanding of the studies presented in this thesis. Chapter 2 focuses on the emergence and the molecular characteristics of ESC-resistant Salmonella enterica serotype Heidelberg isolates in the Netherlands. Their recent emergence was attributed to food-producing animals and poultry products imported from Brazil, while no human infections linked to these contaminated animals and products have been yet documented in the Netherlands (Chapter 2a). In addition, the potential contribution of Kelp gulls of the southern hemisphere in the dissemination of ESC-resistant S. Heidelberg and other Enterobacteriaceae is presented (Chapter 2b). In Chapter 3, Enterobacteriaceae transmission among humans and between humans and animals is discussed. A cross-sectional study among Dutch preschool children and their parents is presented (Chapter 3a), describing the molecular characteristics of the recovered ESC-resistant Enterobacteriaceae and the frequency of intra-familial colonization with identical isolates. The longitudinal presence and molecular diversity of ESC-resistant E. coli from humans and pigs within the same pig farms are presented, confirming transmission events between farmers and their pigs (Chapter 3b). In Chapter 4, SHV extended-spectrum β-lactamases are discussed. The global epidemiology of Enterobacteriaceae encoding SHV ESCases is reviewed in Chapter 4a, highlighting the ubiquity of these extended-spectrum cephalosporinases. Finally, the recent association of blaSHV-12 with IncX3 plasmids among E. coli isolates in the Netherlands, as well as the genetic and functional characteristics of these plasmids contributing to blaSHV-12 emergence are reported (Chapter 4b). In the general discussion (Chapter 5), the results of the thesis are presented and discussed in relation to the epidemiology of ESC-resistant Enterobacteriaceae and the available international literature. Major outcomes of the studies presented in this thesis, using the available molecular microbiology techniques and the incorporation of human and animal components in a “One Health” approach, provide insights on emerging trends among ESC-resistant Enterobacteriaceae of human and animal origin, their cross-transmission within and between reservoirs, as well as the complexity of their “One Health” epidemiology in order to assess the role of animals as a relevant source of such resistant bacteria for humans