RT Journal Article
SR Electronic
T1 Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study
JF Archives of Disease in Childhood - Fetal and Neonatal Edition
JO Arch Dis Child Fetal Neonatal Ed
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP F507
OP F512
DO 10.1136/archdischild-2015-309554
VO 101
IS 6
A1 Alison Kent
A1 Christina Kortsalioudaki
A1 Irene M Monahan
A1 Julia Bielicki
A1 Timothy D Planche
A1 Paul T Heath
A1 Mike Sharland
YR 2016
UL http://fn.bmj.com/content/101/6/F507.abstract
AB 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.