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. 2021 Jan 14;18(2):662.
doi: 10.3390/ijerph18020662.

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

Tamara van Donge  1 , Anne Smits  2   3 , John van den Anker  1   4 , Karel Allegaert  2   5   6
Affiliations

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

Tamara van Donge et al. Int J Environ Res Public Health. .

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.

Keywords: acute kidney injury; adverse drug reaction; amikacin; creatinine; renal impairment; vancomycin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Percentage of extreme low birth weight (ELBW, <1000 g) cases (different gestational age, GA) receiving (a) vancomycin or amikacin exposure and (b) simultaneous vancomycin and amikacin exposure for each postnatal day.
Figure 2
Figure 2
(a) Predicted serum creatinine concentration time profiles for four typical GA ELBW neonates; dotted lines represent serum creatinine concentration under AB exposure, solid lines represent absence of AB exposure. (b) Predicted creatinine clearance under AB exposure; dotted lines represent creatinine clearance under AB exposure, solid lines represent the absence of AB exposure. GA, gestational age; ELBW, extremely low birth weight; AB, antibiotic.
Figure 3
Figure 3
Predicted differences in creatinine concentrations (mg/dL) calculated at the end of each AB exposure period, starting at different postnatal ages and grouped per gestational age. Differences are based on 1000 individual simulation for each gestational age group, including inter-individual variability.
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