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

Background: Gram-negative organisms are common causes of bloodstream infection during the neonatal period and early childhood with high morbidity and mortality as well as increasing concern about associated antimicrobial resistance. Whilst several large sequencing studies have permitted detailed analysis of the population structure of these isolates in adults, equivalent data is lacking in the paediatric population. Methods: We performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children under the age of 18 between 2008 and 2018 in Oxfordshire, UK. Findings: 327 isolates (of which 296 were successfully sequenced) from 287 patients were included in the study. The burden of infection in the paediatric population lies predominantly in neonates. Most infections were caused by E. coli/Klebsiella spp. and Enterobacter hormaechei. There was no evidence of an increasing incidence of E. coli bloodstream infections and for Klebsiella spp. there was some evidence that the incidence decreased slightly. Similarly the proportion of resistant isolates did not change over time, though we did identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of E. coli isolates causing bloodstream infection in neonates and children mirrors that seen in adults. In most cases there was no evidence of transmission between patients/point source acquisition and whole genome sequencing was able to refute a previously suspected outbreak. Conclusion: Our findings support continued use of current empirical treatment guidelines and likely highlight the success of infection control measures in this population. Our data suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis, potentially by vaccination of pregnant women. Clinical trials to further investigate this possibility are warranted.