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

Abstract:

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 (Cmin, Cmax, and Caverage) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized Cmin, Cmax, Caverage, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) 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.

journal_name

Ther Drug Monit

authors

Kim EJ,Oh J,Lee K,Yu KS,Chung JY,Hwang JH,Nam EY,Kim HS,Kim M,Park JS,Song KH,Kim ES,Song J,Kim HB

doi

10.1097/FTD.0000000000000572

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

102-106

issue

1

eissn

0163-4356

issn

1536-3694

journal_volume

41

pub_type

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