An Improved Vancomycin Dosing Strategy in Neonates Using Population Pharmacokinetics and Simulations to Achieve Pharmacodynamic Target Attainment
BACKGROUND Vancomycin is a first-line therapy for neonatal MRSA. Two dosing strategies, postmenstrual age (PMA)-based and serum creatinine (SCR)-based are currently used. This study aimed to evaluate pharmacodynamic (PD) target attainment rates using current dosing regimens, and derive an optimal vancomycin dosing strategy for neonates. METHODS Data were collected for neonates with ≥1 vancomycin serum concentrations. Completed data were not available before September 19, 2013. A population PK model was constructed using NONMEM 7.2. Dosing simulations were performed in MATLAB R2010a. The PD target that best predicts clinical success was defined as a ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) ≥ 400. RESULTS A one-compartment model with first-order elimination was developed. Overall, 1,458 serum concentrations were obtained from 515 patients. The final model established clearance (CL) = 0.042 • (CWT/1.5)^0.72 • (1/ SCR) • (PMA/33) and volume of distribution (V) = 1.04 • (CWT/1.5)^1.06. In simulations, >90% of patients achieved the AUC/MIC target for both current dosing regimens at an MIC 0.5 mg/L. At MICs of 1 and 2, 72% and 12% of the simulated SCR-based dosing profiles achieved the AUC/ MIC target, which was higher than the rates achieved with PMA-based dosing. An improved dosing strategy was developed that featured increased SCR-based doses and dosing intervals from 7.5-30 to 10-40 mg/kg/day. This strategy achieved the AUC/MIC target in 98%, 86%, and 25% of simulations at MICs of 0.5, 1, and 2, respectively. CONCLUSION For neonates, a dosing strategy that incorporates weight and SCR is predicted to achieve the PD target that is predictive of successful therapy in >80% of patients at MICs ≤1 mg/L. Vancomycin is not recommended for isolates with MICs≥2 mg/L.
Sherwin, C. M.,
Desai, P. B.,
& Spigarelli, M. G.
(2014). An Improved Vancomycin Dosing Strategy in Neonates Using Population Pharmacokinetics and Simulations to Achieve Pharmacodynamic Target Attainment. , 167-168.
Presented at the 115th Annual Meeting of the American Society for Clincial Pharmacology and Therapeutics