Vancomycin drug monitoring in infants with CoNS sepsis-target attainment, microbiological response and nephrotoxicity

Viel-Thériault, Isabelle; Martin, Brigitte; Thompson-Desormeaux, Félix; Blackburn, Julie; Moussa, Ahmed; Autmizguine, Julie

doi:10.1038/s41372-019-0519-2

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…However, only three out of 110 subjects developed nephrotoxicity in this study. On the other hand, Viel-Thériault et al ( 42 ) noted nephrotoxicity in 6% of patients, but the authors could not identify a correlation between vancomycin trough and nephrotoxicity. In a study by Tang et al( 43 ), increasing AUC 0−24 was associated with an increase in nephrotoxicity.…”

Section: Discussionmentioning

confidence: 93%

Population pharmacokinetics of vancomycin in very low birth weight neonates

et al. 2023

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IntroductionVancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates.MethodsThis multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0–24 of 400–600 or 400–800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL.ResultsIn total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr).DiscussionWe developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

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Section: Discussionmentioning

confidence: 93%

Population pharmacokinetics of vancomycin in very low birth weight neonates

et al. 2023

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“…Based on both in vitro and in vivo observations, the assumed mechanism also relates to dose-dependent intracellular accumulation and oxidative damage in the renal tubular cells [15]. In neonates, the evidence on vancomycin nephrotoxicity has been summarized and is suggested to occur in 1-9% of exposed cases [16][17][18]. These incidences are supported by two more recent reports [19,20].…”

Section: Aminoglycosides and Vancomycin Related Acute Kidney Injury: Developmental Toxicologymentioning

confidence: 93%

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

Donge

Smits

Anker

et al. 2021

IJERPH

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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.

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Section: Aminoglycosides and Vancomycin Related Acute Kidney Injury: mentioning

confidence: 99%

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

Donge¹,

Smits²,

Anker³

et al. 2020

Preprint

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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.

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Vancomycin drug monitoring in infants with CoNS sepsis-target attainment, microbiological response and nephrotoxicity

Cited by 9 publications

References 25 publications

Population pharmacokinetics of vancomycin in very low birth weight neonates

Population pharmacokinetics of vancomycin in very low birth weight neonates

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

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

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