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Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study
  1. Alison Kent1,
  2. Christina Kortsalioudaki1,
  3. Irene M Monahan2,
  4. Julia Bielicki1,
  5. Timothy D Planche2,3,
  6. Paul T Heath1,
  7. Mike Sharland1
  8. on behalf of the Neonatal Gram Negative MIC group
    1. 1Paediatric Infectious Disease Research Group, St George's, University of London, London, UK
    2. 2Institute of Infection and Immunity, St George's, University of London, London, UK
    3. 3Department of Medical Microbiology, St George's Healthcare NHS Trust, London, UK
    1. Correspondence to Dr Alison Kent, Paediatric Infectious Disease Research Group, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK; alisonkent{at}


    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 included Escherichia coli (51%), Klebsiella spp (23%) and Enterobacter spp (22%). 10-day attributable mortality was 18.1% (21 patients) with the highest mortality from Pseudomonas aeruginosa infections. 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 loge increase 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.

    • Infectious Diseases
    • Intensive Care
    • Microbiology
    • Neonatology
    • Therapeutics

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    • These data have been previously presented in part at ESPID annual conference, 15 May 2015, Leipzig, Germany. Abstract number 484.

    • Collaborators Neonatal Gram-negative MIC group: Alison Bedford-Russell; Barbara Bromage; John Chang; Alleyna Claxton; Andrew Collinson; Nicholas Embleton; Jim Grey; Olga Kapellou; Manjusha Narayanan; Timothy Neal; Vanessa Perks; Tim Scorrer; Mark Turner and Mary Twagira.

    • Contributors All authors contributed to the design of the study and reviewed the draft manuscript. In addition, AK, CK, IMM and TDP conducted the microbiological and statistical analyses.

    • Funding Action Medical Research (Grant number: SP4650).

    • Competing interests PTH was a member of the National Institute for Health and Clinical Excellence Antibiotics for Early Onset Neonatal Infection Guideline Development Group.

    • Ethics approval National Research Ethics Service Committee London—Surrey Borders.

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