title: Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study.
abstract: BACKGROUND
  Neonatal gram-negative (GN) infections are associated with high mortality and morbidity. Early appropriate antibiotic treatment is vital and gentamicin is the most frequently used antibiotic on neonatal units (NNUs). Antimicrobial breakpoints are predominantly based on adult data and the relationship between minimum inhibitory concentrations (MICs) and outcome in neonates is unclear. We aimed to determine the MIC of GN pathogens causing neonatal infections and relate this to clinical outcomes.
  
  
  METHODS
  MICs for eight antibiotics plus extended spectrum β-lactamase (ESBL) production were determined for invasive GN bacterial isolates from eight UK NNUs. European Committee on Antimicrobial Susceptibility Testing breakpoints were applied. MIC was correlated with clinical outcome using multivariable regression analysis.
  
  
  RESULTS
  118 isolates from 116 patients were analysed. The median birth gestation and postnatal age was 27 weeks (IQR 24.6-32.3) and 20 days (IQR 5-44), respectively. Pathogens includedEscherichia coli(51%),Klebsiellaspp (23%) andEnterobacterspp (22%). 10-day attributable mortality was 18.1% (21 patients) with the highest mortality fromPseudomonas aeruginosainfections. ESBL producers accounted for 13.8% of the isolates. In regression analysis, increasing gentamicin MIC was associated with increased mortality in gentamicin treated patients across the full MIC range (OR per logeincrease in MIC: 2.29; 95% CI 1.23 to 4.26, p=0.009), including susceptible isolates only (MIC ≤4) (OR 3.05; 95% CI 1.10 to 8.46, p=0.032).
  
  
  CONCLUSIONS
  Neonatal mortality from GN infections remains high and is associated with increasing gentamicin MIC, even for isolates deemed susceptible. A better understanding of population-specific MICs and aminoglycoside dosing is required to guide empiric antibiotic treatment.
authors.affiliation: Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
authors.forename: Alison
authors.identifier: http://orcid.org/0000-0002-3196-2355
authors.initials: A
authors.lastname: Kent
authors.affiliation: Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Kortsalioudaki
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Monahan
authors.affiliation: Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Bielicki
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, London, UK.|Department of Medical Microbiology, St George's Healthcare NHS Trust, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Planche
authors.affiliation: Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
keywords: Infectious Diseases; Intensive Care; Microbiology; Neonatology; Therapeutics