Pharmacokinetic Characteristics and Limited Sampling Strategies for Therapeutic Drug Monitoring of Colistin in Patients with Multidrug-Resistant Gram-Negative Bacterial Infections

Background:Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin-treated patients in Korea.Methods:In a prospective study, we analyzed PK characteristics in 15 patients who intravenously received colistin methanesulfonate twice per day. Colistin methanesulfonate doses were adjusted based on renal function of the subjects. The appropriate blood sampling points for TDM were evaluated by analyzing the correlations between the PK parameters and the plasma concentrations at each time point.Results:The mean values for the minimum, maximum, and average concentrations (C_min, C_max, and C_average) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized C_min, C_max, C_average, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUC_last) showed negative correlations with the creatinine clearance. The combination of the 0- and 2-hour post-dose plasma concentrations was evaluated as the appropriate sampling point for TDM. Two patients reported nephrotoxic adverse events during colistin administration.Conclusions:Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM.