An Audit to Evaluate Vancomycin Therapeutic Drug Monitoring in a Neonatal Intensive Care Unit.

BACKGROUND: Therapeutic drug monitoring (TDM) is routinely used for optimization of vancomycin therapy, because of exposure-related efficacy and toxicity, in addition to significant variability in pharmacokinetics, which leads to unpredictable drug exposure. OBJECTIVE: The aim of this study was to evaluate target attainment and TDM of vancomycin in neonates. METHODS: The authors conducted a retrospective study and collected data from medical records of all neonates who received vancomycin therapy in the neonatal intensive care unit between January 2019 and December 2019. The primary outcome was the proportion of vancomycin courses that reached target trough concentrations of 10-20 mg/L based on appropriate TDM samples collection. Secondary outcomes included proportion of courses with appropriate dose and dose frequency, and proportion of patients who achieved target concentrations after the first dose adjustment. RESULTS: In total, 69 patients were included, with 129 vancomycin courses. The median initial vancomycin trough concentration was 12 (range: 4-36) mg/L. The target trough concentration was achieved in 75% of courses after the initial dose with appropriate TDM, and 84% of courses after TDM-guided dose adjustments. Patients were dosed appropriately in 121/129 courses and TDM was performed correctly according to protocol in 51/93 courses. A dose adjustment was performed in 18/29 courses, to increase target attainment. CONCLUSIONS: This study showed that there is a need for an increase in dose to improve target attainment. There is also a need to explore more effective TDM strategies to increase the proportion of neonatal patients attaining vancomycin target trough concentrations.

Bayesian Vancomycin Model Selection for Therapeutic Drug Monitoring in Neonates.

BACKGROUND AND OBJECTIVE: Pharmacokinetic models can inform drug dosing of vancomycin in neonates to optimize therapy. However, the model selected needs to describe the intended population to provide appropriate dose recommendations. Our study aims to identify the population pharmacokinetic (PopPK) model(s) with the best performance to predict vancomycin exposure in neonates in our hospital. METHODS: Relevant published PopPK models for vancomycin in neonates were selected based on demographics and vancomycin dosing strategy. The predictive performance of the models was evaluated in Tucuxi using a local cohort of 69 neonates. Mean absolute error (MAE), relative bias (rBias) and relative root mean square error (rRMSE) were used to quantify the accuracy and precision of the predictive performance of each model for three different approaches: a priori, a posteriori, and Bayesian forecasting for the next course of therapy based on the previous course predictions. A PopPK model was considered clinically acceptable if rBias was between ± 20 and 95% confidence intervals included zero. RESULTS: A total of 25 PopPK models were identified and nine were considered suitable for further evaluation. The model of De Cock et al. 2014 was the only clinically acceptable model based on a priori [MAE 0.35 mg/L, rBias 0.8 % (95% confidence interval (CI) - 7.5, 9.1%), and rRMSE 8.9%], a posteriori [MAE 0.037 mg/L, rBias - 0.23% (95% CI - 1.3, 0.88%), and rRMSE 6.02%] and Bayesian forecasting for the next courses [MAE 0.89 mg/L, rBias 5.45% (95% CI - 8.2, 19.1%), and rRMSE 38.3%) approaches. CONCLUSIONS: The De Cock model was selected based on a comprehensive approach of model selection to individualize vancomycin dosing in our neonates.

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.