Abstract

Extended-spectrum cephalosporin-resistant (ESCR) Enterobacteriaceae pose a serious infection control challenge for public health. The emergence of the ESCR phenotype is mostly facilitated by plasmid-mediated horizontal extended-spectrum β-lactamases (ESBLs) and AmpC gene transfer within Enterobacteriaceae. Current data regarding the plasmid contribution to this emergence within the Dutch human population is limited. Hence, the aim of this study was to gain insight into the role of plasmids in the dissemination of ESBL/AmpC genes inside Dutch households with preschool children and precisely delineate co-colonization. In 87 ESCR Enterobacteriaceae from fecal samples of parents and preschool children within 66 Dutch households, genomic localization, plasmid type and insertion sequences linked to ESBL/AmpC genes were determined. Chromosomal location of ESBL/AmpC genes was confirmed when needed. An epidemiologically relevant subset of the isolates based on household co-carriage was assessed by Multilocus Sequence Typing and Pulsed-Field Gel Electrophoresis for genetic relatedness. The narrow-host range I1α and F plasmids were the major facilitators of ESBL/AmpC-gene dissemination. Interestingly, we documented a relatively high occurrence of chromosomal integration of typically plasmid-encoded ESBL/AmpC-genes. A high diversity of non-epidemic Escherichia coli sequence types (STs) was revealed; the predominant STs belonged to the pandemic lineages of extraintestinal pathogenic E. coli ST131 and ST69. Intra-familiar co-carriage by identical ESCR Enterobacteriaceae was documented in 7 households compared to 14 based on sole gene typing, as previously reported. Co-carriage was more frequent than expected based on pure chance, suggesting clonal transmission between children and parents within the household.

Highlights

  • Extended-spectrum cephalosporin-resistant (ESCR)Enterobacteriaceae have emerged worldwide as a significant cause of hospital, health care- and community-associated infections (Paterson and Bonomo, 2005; Jacoby, 2009; Pitout, 2013; Woerther et al, 2013)

  • The diversity of E. coli sequence types (STs) found within Dutch preschool children and parents suggests that commensal E. coli act as reservoir of ESBL/AmpC genes

  • The most prevalent STs were the pandemic lineages of extraintestinal pathogenic E. coli (ExPEC) ST131 and ST69 known to cause urinary and bloodstream infections, among others (Riley, 2014)

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Summary

Introduction

Extended-spectrum cephalosporin-resistant (ESCR)Enterobacteriaceae have emerged worldwide as a significant cause of hospital-, health care- and community-associated infections (Paterson and Bonomo, 2005; Jacoby, 2009; Pitout, 2013; Woerther et al, 2013). ESBL and AmpC β-lactamases belong to different structural and functional classification groups (Ambler, 1980; Bush et al, 1995), resulting in differences in their hydrolytic spectrums. They are both able to hydrolyse the oxyimino-β-cephalosporins commonly used in clinical practice, such as cefotaxime and ceftazidime (Paterson and Bonomo, 2005; Jacoby, 2009). Transmission of ESCR Enterobacteriaceae within households and subsequently amongst the community has been documented to occur in multiple ways: from patients with communityacquired infections (Valverde et al, 2008), patients recently discharged or cared for in a hospital (Lo et al, 2010; Mihaila et al, 2010; Hilty et al, 2012; Löhr et al, 2013; Haverkate et al, 2017), infants colonized after neonatal ICU admission (Strenger et al, 2013), adopted children from countries with high prevalence of ESCR Enterobacteriaceae (Tande et al, 2010) and from international travelers to their household contacts (Arcilla et al, 2017)

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