Clinical pharmacokinetics of vancomycin in the neonate: a review

Abstract

Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates.

A propensity-matched cohort study of vancomycin-associated nephrotoxicity in neonates

“…An antibiotic that occasionally causes mild renal dysfunction may not warrant a change in the clinical management of a neonate with a potentially life-threatening infection but an agent that increased the risk of renal failure would need to be carefully weighed. The implications of this finding also extend to therapeutic drug monitoring, which is logistically and ethically challenging for vulnerable patient populations, especially neonates 44. This study lends support to the observation that neonates may be less susceptible to vancomycin-induced nephrotoxicity compared with older children and adults.…”

Coagulase negative staphylococcal sepsis in neonates: do we need to adapt vancomycin dose or target?

“…Prospectively designed studies with rich or semi-rich sampling are scarce or outdated in neonates [40]. At present NeoVanc project sponsored by EU FP7 is aiming to fill these gaps.…”

Do we really need continuous vancomycin infusion in neonates?

“…The effect of postnatal age and kidney function on the weight-normalised clearance of vancomycin has been previously shown by multiple investigators 2. The larger volume of distribution and a lower clearance in the newborn population compared with adults seem to mandate an initial loading dose to reach the timely steady-state concentration 2 3. These limitations can certainly contribute to the high degree of off-target vancomycin concentrations (5.1–61.5 mg/L) that was observed in the control group of this study.…”

“…The dosing regimens in the latter two hospitals were either universal, regardless of the postnatal age and kidney function or did not include an initial loading dose. The effect of postnatal age and kidney function on the weight-normalised clearance of vancomycin has been previously shown by multiple investigators 2. The larger volume of distribution and a lower clearance in the newborn population compared with adults seem to mandate an initial loading dose to reach the timely steady-state concentration 2 3.…”