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Epidemiology and healthcare factors associated with neonatal enterococcal infections
  1. Joanna Wang1,2,
  2. Christina Kortsalioudaki3,
  3. Paul T Heath3,
  4. Jim Buttery2,4,5,
  5. Paul Clarke6,
  6. Despoina Gkentzi7,
  7. Mark Anthony1,
  8. Kenneth Tan2,4
  9. on behalf of the neonIN network
    1. 1Newborn Care Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
    2. 2Department of Paediatrics, Monash University, Melbourne, Victoria, Australia
    3. 3Paediatric Infectious Diseases Research Group, Infection and Immunity, St George’s University of London, London, UK
    4. 4Monash Children’s Hospital, Melbourne, Victoria, Australia
    5. 5Monash Centre for Health Research and Implementation, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
    6. 6Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
    7. 7Department of Paediatrics, University General Hospital of Patras, Patras, Greece
    1. Correspondence to Dr Kenneth Tan, Monash Childre’s Hospital, Melbourne, VIC 3168, Australia; kenneth.tan{at}


    Objective To investigate the epidemiology and healthcare factors associated with late-onset neonatal enterococcal infections.

    Design Multicentre, multinational retrospective cohort study using prospectively collected infection data from a neonatal infection surveillance network between 2004 and 2016; this was supplemented with healthcare data from a questionnaire distributed to participating neonatal units.

    Setting Sixty neonatal units across Europe (UK, Greece, Estonia) and Australia.

    Patients Infants admitted to participating neonatal units who had a positive culture of blood, cerebrospinal fluid or urine after 48 hours of life.

    Results In total, 414 episodes of invasive Enterococcus spp infection were reported in 388 infants (10.1% of a total 4083 episodes in 3602 infants). Enterococcus spp were the second most common cause of late-onset infection after coagulase-negative Staphylococcus spp and were strongly associated with necrotising enterocolitis (NEC) (adjusted OR 1.44, 95% CI 1.02 to 2.03, p=0.038), total parenteral nutrition (TPN) (adjusted OR 1.34, 95% CI 1.06 to 1.70, p=0.016), increasing postnatal age (per 1-week increase: adjusted OR 1.04, 95% CI 1.02 to 1.06, p<0.001) and decreasing birth weight (per 1 kg increase: adjusted OR 0.85, 95% CI 0.74 to 0.97, p=0.017). There was no evidence that inadequate nurse to patient staffing ratios in high-dependency units were associated with a higher risk of enterococcal infections.

    Conclusions Enterococcus spp were the second most frequent cause of late-onset infections. The association between enterococcal infections, NEC and TPN may inform empiric antimicrobial regimens in these contexts and provide insights into reducing these infections.

    • enterococcus
    • infection
    • neonatal
    • epidemiology
    • healthcare

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    • Contributors PTH developed the neonIN network and JB conceptualised this study. JW, MA, KT, CK, PTH and JB contributed to the study and questionnaire design. CK and MA supervised the acquisition of data for analysis. KT and MA supervised data analysis. JW, KT, MA, PTH, CK and JB contributed to data interpretation. JW performed the analyses and drafted the manuscript. KT, MA, PTH, JB, CK, PC and DG critically revised and approved the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Not required

    • Ethics approval neonIN has ethics approval from the Health Research Authority (05/Q0806/34+5).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators M Ezzat, M Bohatschek, C Cane, I Storey, S Wallis, R Geethanath, J Campbell, J Chang, T Watts, O Kapellou, S Luck, M Turner, S Ali, E Gasiorowski, M Lal, N Embleton, S Job, T Scorrer, S Sundaram, A Collinson, N Osborne, M Hall, E Pilling, L Hamilton, G Atreja, J Davis, P Reynolds, P Satodia.