Profound pharmacokinetic alterations involving volume of distribution and clearance may impair the achievement of adequate antimicrobial serum concentrations in major burn patients. Gentamicin pharmacokinetic analysis was performed in a major burn victim with 90% of total body surface area affected and complicated by septic shock due to Serratia marcescens (minimum inhibitory concentration [MIC] = 2 mg/L). Gentamicin 240 mg was administered as a 30-min intravenous infusion, and plasma samples were obtained at 0-, 0.5-, 1-, 3- and 6-hour time points after the start of infusion. Gentamicin peak concentrations (CMAX) were 11.9 mg/L, providing for the achievement of an inadequate CMAX/MIC target. Volume of distribution was more than double as compared to healthy volunteers (0.44 vs. 0.18 L/Kg), while clearance was quite similar (5.21 vs. 5.42 L/h). Higher dosage (7-10 mg/Kg) coupled with adaptive therapeutic drug monitoring should be implemented in order to maximize gentamicin dosing schedule in critical challenging situations.
Reference:Gatti, M. (2020) Pharmacokinetic analysis investigating gentamicin dosing in a major burned patient complicated by septic shock. Journal of Chemotherapy. March 3rd. doi: 10.1080/1120009X.2020.1733335. (Epub ahead of print).