Optimizing colistin dosing: Is a loading dose necessary?

Abstract

Purpose. Published literature on the pharmacokinetics and effectiveness of colistin loading doses is reviewed. Summary. Colistin is increasingly used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria (GNB). A literature search identified seven reports on studies of colistin loading doses. All reviewed studies involved small samples of critically ill patients, with considerable variation in the colistin products and loading doses used. Pharmacokinetic studies indicated that because of the slow rate of conversion of the prodrug colistimethate sodium to the active drug colistin and the long half-life of colistin, it can take two to three days to attain adequate colistin concentrations without a loading dose. The clinical effectiveness of colistin loading doses was evaluated in two studies, neither involving the use of a comparator group. In one of those studies, clinical cure and bacteriological clearance were reported in 82.1% and 73.9% of cases, respectively; in the other, clinical resolution was reported in 77% of patients. Two studies were conducted to compare clinical outcomes of colistin loading-dose regimens and standard regimens with no loading dose; while use of a loading dose was associated with a higher cure rate (63.0% versus 41.3%, p = 0.04) in one study, no improvement in clinical outcomes was reported in the other study. Conclusion. Published data on the effectiveness of colistin loading doses are limited. The available evidence suggests that it may be necessary to administer a colistin loading dose in severe and life-threatening infections due to MDR GNB.