Pharmacokinetics of Colistin Methanesulfonate and Colistin in a Critically Ill

Intravenous colistin methanesulfonate (CMS) is increasingly the last line of defense for multidrug-resistant gram-negative bacteria and is now being used as “salvage ” therapy in critically ill patients (1, 7, 9, 11). CMS is converted in vivo to colistin, and these two entities have substantially different pharmaco-kinetics, antibacterial activities, and toxicities (7), and there-fore it is important to understand the dispositions of both. Patients who are currently being treated with CMS include many in the intensive care setting with multiple organ dysfunc-tions and receiving renal replacement therapy (10). Goodwin et al. reported the effects of renal impairment, peritoneal di-alysis, and hemodialysis on the concentrations of CMS in se-rum (3); unfortunately, the microbiological assays employed failed to measure colistin and CMS separately. Moreover, the efficiency of the hemodialyzer used in the 1968 report of Good