Recommendations of Gentamicin Dose Based on Different Pharmacokinetic/Pharmacodynamic Targets for Intensive Care Adult Patients: A Redefining Approach

In addition to the maximum plasma concentration (C ) to the minimum inhibitory concentration (MIC) ratio, the 24-hour area under the concentration-time curve (AUC ) to MIC has recently been suggested as pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy and safety in once-daily dosing of gentamicin (ODDG) in critically ill patients. This study aimed to predict the optimal effective dose and risk of nephrotoxicity for gentamicin in critically ill patients for two different PK/PD targets within the first 3 days of infection. The gathered pharmacokinetic and demographic data in critically ill patients from 21 previously published studies were used to build a one-compartment pharmacokinetic model. The Monte Carlo Simulation (MCS) method was conducted with the use of gentamicin once-daily dosing ranging from 5-10 mg/kg. The percentage target attainment (PTA) for efficacy, C /MIC ~8-10 and AUC /MIC ≥110 targets, were studied. The AUC >700 mg⋅h/L and C >2 mg/L were used to predict the risk of nephrotoxicity. Gentamicin 7 mg/kg/day could achieve both efficacy targets for more than 90% when the MIC was 700 mg⋅h/L was small, but the risk was greater when applying a C target >2 mg/L. Considering both targets of Cmax/MIC ~8-10 and AUC /MIC ≥110, an initial gentamicin dose of 8 mg/kg/day should be recommended in critically ill patients for pathogens with MIC of ≤1 mg/L. Clinical validation of our results is essential.