Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study

Alison Kent; Christina Kortsalioudaki; Irene M Monahan; Julia Bielicki; Timothy D Planche; Paul T Heath; Mike Sharland; Neonatal Gram Negative MIC group

doi:10.1136/archdischild-2015-309554

Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study

Arch Dis Child Fetal Neonatal Ed. 2016 Nov;101(6):F507-F512. doi: 10.1136/archdischild-2015-309554. Epub 2016 Mar 7.

Authors

Alison Kent¹, Christina Kortsalioudaki¹, Irene M Monahan², Julia Bielicki¹, Timothy D Planche^{2

3}, Paul T Heath¹, Mike Sharland¹; Neonatal Gram Negative MIC group

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, Mary Twagira

Affiliations

¹ Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.
² Institute of Infection and Immunity, St George's, University of London, London, UK.
³ Department of Medical Microbiology, St George's Healthcare NHS Trust, London, UK.

PMID: 26951742
DOI: 10.1136/archdischild-2015-309554

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 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 log_e 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.

Keywords: Infectious Diseases; Intensive Care; Microbiology; Neonatology; Therapeutics.

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