Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria.
Sam Lipworth, Karina-Doris Vihta, Tim Davies, Sarah Wright, Merline Tabirao, Kevin Chau, Alison Vaughan, James Kavanagh, Leanne Barker, Sophie George, Shelley Segal, Stephane Paulus, Lucinda Barrett, Sarah Oakley, Katie Jeffery, Lisa Butcher, Tim Peto, Derrick Crook, Sarah Walker, Seilesh Kadambari, Nicole Stoesser
Author Information
Sam Lipworth: Nuffield Department of Medicine, University of Oxford, Oxford, UK. ORCID
Karina-Doris Vihta: Nuffield Department of Medicine, University of Oxford, Oxford, UK. ORCID
Tim Davies: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sarah Wright: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Merline Tabirao: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Kevin Chau: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alison Vaughan: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
James Kavanagh: Nuffield Department of Medicine, University of Oxford, Oxford, UK. ORCID
Leanne Barker: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sophie George: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Shelley Segal: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Stephane Paulus: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Lucinda Barrett: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Sarah Oakley: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Katie Jeffery: Oxford University Hospitals NHS Foundation Trust, Oxford, UK. ORCID
Lisa Butcher: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Tim Peto: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Derrick Crook: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sarah Walker: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Seilesh Kadambari: Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Nicole Stoesser: Nuffield Department of Medicine, University of Oxford, Oxford, UK. ORCID
Background: Gram-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. Methods: We perform an epidemiological and sequencing based analysis of Gram-negative bloodstream infections (327 isolates (296 successfully sequenced) from 287 patients) in children <18 years old between 2008 and 2018 in Oxfordshire, UK. Results: Here we show that the burden of infection lies predominantly in neonates and that most infections are caused by spp. and . There is no evidence in our setting that the proportion of antimicrobial resistant isolates is increasing in the paediatric population although we identify some evidence of sub-breakpoint increases in gentamicin resistance. The population structure of BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportions of O-antigen serotypes. In most cases in our setting there is no evidence of transmission/point-source acquisition and we demonstrate the utility of whole genome sequencing to refute a previously suspected outbreak. Conclusions: Our 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.
