Antimicrobial agents and chemotherapy
-
Antimicrob. Agents Chemother. · Dec 2014
Multicenter StudyNew colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale.
Colistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. ⋯ We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.