Dosing of vancomycin and target attainment in neonates: a systematic review.

Introduction: Neonatal infections caused by Gram-positive bacteria are commonly treated with vancomycin. However, there is a lack of agreement on the optimal vancomycin dosing regimen and corresponding vancomycin exposure to correlate with efficacy and toxicity.

Objectives: This review aimed to evaluate dosing of vancomycin in neonates, therapeutic target attainment and clinical toxicity and efficacy outcomes.

Methods: Two electronic databases - Embase and PubMed (Medline) - were systematically searched between 1995-2020. Studies that reported dosing regimens, drug concentrations, toxicity, and efficacy of vancomycin in neonates were eligible for inclusion. Descriptive analysis and a narrative synthesis were performed.

Results: The systematic review protocol was registered with the PROSPERO International Prospective Register of Systematic reviews in 2020 (registration number: CRD42020219568). Twenty-four studies were included for final analysis. Overall, the data from the included studies showed a great degree of heterogeneity. Therapeutic drug monitoring practices were different between institutions. Although most studies used trough concentration with a target range of 10-20 mg/L, target attainment was different across the studies. The probability of target attainment was < 80% in all tested dosing algorithms. Few studies reported on vancomycin efficacy and toxicity.

Conclusion: This is a comprehensive overview of dosing strategies of vancomycin in neonates. There was inadequate evidence to propose an optimal therapeutic regimen in the newborn population, based on the data obtained, due to the heterogeneity in the design and objectives of the included studies. Consistent and homogeneous comparative randomised clinical trials are needed to identify a dosing regimen with a probability of target attainment of > 90% without toxicity.