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Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in Extreme Low Birth Weight Neonates

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  • Tamara van Donge

    (Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4001 Basel, Switzerland)

  • Anne Smits

    (Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
    Neonatal Intensive Care Unit, University Hospitals Leuven, 3000 Leuven, Belgium)

  • John van den Anker

    (Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4001 Basel, Switzerland
    Division of Clinical Pharmacology, Children’s National Health Hospital, Washington, DC 20010, USA)

  • Karel Allegaert

    (Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
    Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium
    Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015 Rotterdam, The Netherlands)

Abstract

Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 extremely low birth weight (<1000 g, ELBW) neonates (4036 observations) was enhanced with data on vancomycin and/or amikacin exposure to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling. Results: Seventy-seven percent of ELBW patients were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in a modest increase in serum creatinine and a transient decrease in creatinine clearance. The serum creatinine increase was dependent on gestational age, illustrated by a decrease with 56% in difference in serum creatinine between a 24 or 32-week old neonate, when exposed in the 3rd week after birth. Conclusions: A previously described model was used to explore and quantify the impact of amikacin or vancomycin exposure on creatinine dynamics. Such tools serve to explore minor changes, or compare minor differences between treatment modalities.

Suggested Citation

  • Tamara van Donge & Anne Smits & John van den Anker & Karel Allegaert, 2021. "Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in Extreme Low Birth Weight Neonates," IJERPH, MDPI, vol. 18(2), pages 1-11, January.
  • Handle: RePEc:gam:jijerp:v:18:y:2021:i:2:p:662-:d:480278
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    References listed on IDEAS

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    1. Asma Al-Turkait & Lisa Szatkowski & Imti Choonara & Shalini Ojha, 2020. "Review of Drug Utilization Studies in Neonatal Units: A Global Perspective," IJERPH, MDPI, vol. 17(16), pages 1-32, August.
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