Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in ELBW Neonates

Background: Disentangling adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates. Vancomycin and amikacin are perceived as nephrotoxic and often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 ELBW neonates (4036 serum creatinine observations) was enhanced with data on individual administration of vancomycin and/or amikacin to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling analysis. Results: Of our ELBW patients, 77% were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in transient lower overall creatinine clearance and a modest increase in serum creatinine. Dependency on gestational age was observed in the difference in serum creatinine when exposed to antibiotics during the third week after birth (difference in creatinine for a neonate at 24 weeks gestation decreased with 56% for a 32-week-old neonate). Conclusions: A previously described model on creatinine dynamics was used to explore and quantify the impact amikacin or vancomycin exposure on creatinine dynamics. Such tools can be used to explore minor changes, or compare minor differences between treatment modalities.