Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Abstract

Aim: In animal studies, aminoglycosides induced ductus arteriosus relaxation in a dose-dependent fashion. We tested the hypothesis that antibiotic treatment of preterm infants with aminoglycosides is associated with higher rates of surgical patent ductus arteriosus (PDA) closure.

Methods: Preterm infants (birthweight <1000 grams or gestational age <29 weeks) enrolled in 62 German neonatal intensive care units (NICUs) were analysed. NICUs were stratified according to the use of aminoglycosides as first-line antibiotics.

Results: Baseline data were not different when NICUs using aminoglycosides (n = 9965 infants) were compared to NICUs using other antibiotics (n = 1948 infants). Rates of surgical PDA closure were 5.9% for NICUs using aminoglycosides; 6.2% for units using gentamicin; and 5.0% for NICUs using tobramycin compared to 4.1% in NICUs using other antibiotics (P < .001, P < .001 and P = .140, respectively, Fisher's exact test). Indomethacin and ibuprofen use was more common in NICUs using aminoglycosides (41% vs 33%, P < .001, Fisher's exact test). Gentamicin trough levels were higher in NICUs with surgical closure rates above the mean (median 2.0 µg/mL, inter-quartile range 0.8-4.0 µg/mL vs 1.2 µg/mL, IQR 0.8-1.7, P < .001, Mann-Whitney U test).

Conclusion: First-line antibiotic treatment of preterm infants with aminoglycosides was associated with higher rates of surgical PDA closure.

Keywords: aminoglycosides; extremely preterm infants; patent ductus arteriosus; surgical ligation.