Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria in Oxfordshire, UK

Abstract

AbstractObjectivesGram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population.MethodsWe performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children <18 years old between 2008 and 2018 in Oxfordshire, UK.Results327 isolates (296 successfully sequenced) from 287 patients were included. The burden of infection was predominantly in neonates (124/327[38%]). Most infections were caused by Escherichia coli (149/327[46%])/Klebsiella spp. (69/327[21%]) and Enterobacter hormaechei (34/327[10%]). There was no evidence of an increasing incidence of E. coli BSIs (IRRy 0.96, 95%CI 0.90-1.30, p=0.30) and for Klebsiella spp. there was some evidence that the incidence decreased slightly (IRRy 0.91, 95%CI 0.83-1.00, p=0.06). Similarly the proportion of antimicrobial resistant (across all antimicrobial classes evaluated) isolates did not change over time, though we did identify some evidence of sub-breakpoint increases in gentamicin resistance IRRy 1.86, 95%CI 1.33-2.58, pheterogeneity=0.002. The population structure of E. coli BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportion of O-antigen serotypes covered by the ExPEC-4V vaccine. In most cases there was no evidence of transmission/point-source acquisition and whole genome sequencing was able to refute a previously suspected Serratia marcescens outbreak.ConclusionOur findings support continued use of current empirical treatment guidelines and suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis.