What is the right gentamicin dose for multiple trauma patients? A Monte Carlo simulation exploration study

Abstract

Background: The appropriate dose of gentamicin is important to prevent and treat infections. The study aimed to determine the optimal dose of gentamicin to achieve the probability of pharmacokinetic/pharmacodynamic (PK) targets for efficacy and safety in multiple trauma patients. Methods: PK parameters of gentamicin in multiple trauma patients were gathered to develop a one-compartment PK model for prediction. The Monte Carlo simulation method was performed. The 24-h area under the concentration time curve to the minimum inhibitory concentration ratio (AUC24h/MIC) ≥50 was defined for the infection prevention target. AUC24h/MIC ≥110 or the maximum serum concentration to MIC ratio ≥8–10 was for the treatment of serious Gram-negative infection target. The risk of nephrotoxicity was the minimum serum concentration ≥2 mg/L. The optimal dose of gentamicin was determined when the efficacy target was >90% and the risk of nephrotoxicity was lowest. Results: The optimal gentamicin dose to prevent infection when the MIC was <1 mg/L was 6–7 mg/kg/day. A higher dose of gentamicin up to 10 mg/kg/day could not reach the target for treating serious Gram-negative infection when the expected MIC was ≥1 mg/L. The probability of nephrotoxicity was minimal at 0.2–4% with gentamicin doses of 5–10 mg/kg/day for 3 days. Conclusions: Once daily gentamicin doses of 6–7 mg/kg are recommended to prevent infections in patients with multiple trauma. Gentamicin monotherapy could not be recommended for serious infections. Further clinical studies are required to confirm our results.