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.

Mouse models of patent ductus arteriosus (PDA) and their relevance for human PDA

“…50,51,96 Aminoglycoside antibiotics (gentamicin) 97 and certain antacids, which inhibit cytochrome P450 enzymes (cimetidine) 98 also cause PDA in mice. A recent cohort study confirmed the role of gentamicin in human PDA 99 and cimetidine studies originated from human clinical observations. 98,100 Antibiotics, antacids, and COX inhibitors are routinely used in the treatment of pregnant women and neonates, emphasizing the utility of these animal models.…”

Gentamicin in Neonates with Hemodynamically Significant Patent Ductus Arteriosus

“…A recent study from eight neonatal intensive care units in Europe revealed that the use of gentamicin and tobramycin in neonates with hsPDA increases the risk of surgical intervention for PDA closure with an odds ratio of 1.6 and 1.3, respectively. [ 18 ] However, the treatment for hsPDA varied between the neonatal units, including the criteria for surgical intervention that has not been considered by the authors in that study. Cakir et al .…”