Optimal loading and maintenance doses for continuous infusion of vancomycin

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Our aim was to develop a rational approach for optimized dosage of vancomycin given in continuous infusion in critically ill patients” Vu et al (2019).

Abstract:

Despite extensive clinical use, only limited data is available regarding optimal loading and maintenance doses of vancomycin in critically ill patients. Our aim was to develop a rational approach for optimized dosage of vancomycin given in continuous infusion in critically ill patients. Vancomycin pharmacokinetic (PK) data (total serum concentrations) were obtained from 55 ICU patients (Bach Mai Hospital, Hanoi, Vietnam) receiving a 20 mg/kg loading dose followed by continuous infusion stratified by creatinine clearance (CLCr). Population PK modelling and Monte Carlo simulations were performed using NONMEM for a target of 20-30 mg/L to optimize efficacy and minimize nephrotoxicity. A two-compartment model with first-order elimination best fitted the PK data with central and peripheral volume of distribution of 1.01 and 2.39 L/kg, respectively (allometric scaling to a 70kg-standard subject). The population total clearance of 3.63 L/h was only explained by renal function in covariate and final model. The simulations showed that a 25-mg/kg loading dose infused over 90 minutes was optimal to reach the target range. The optimal maintenance doses for low renal function (CLCr <45 mL/min) was 1000 to 1500 mg/day. For augmented renal clearance (CLCr > 130 mL/min) patients the dose should be up to 3500 mg/day or even 4500 mg/day to achieve adequate exposure. This simulated maintenance doses were larger than previously proposed for non-ICU patients. In conclusion, large loading and maintenance doses of vancomycin are generally needed in critically ill patients. Because of high interindividual variability in vancomycin PK, drug monitoring may still be necessary.

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Reference:

Vu, D.H., Nguyen, D.A., Delattre, I.K., Ho, T.T., Do, H.G., Pham, H.N., Dao, X.C., Tran, N.T., Nguyen, G.B., Van Bambeke, F., Tulkens, P.M. and Nguyen, H.A. (2019) Determination of optimal loading and maintenance doses for continuous infusion of vancomycin in critically ill patients: population pharmacokinetic modelling and simulations for improved dosing schemes. International Journal of Antimicrobial Agents. October 7th. doi: 10.1016/j.ijantimicag.2019.09.018. .

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