Central nervous system infections caused by Gram-negative bacteria susceptible only to
colistin are rare but life-threatening and increasing in prevalence. Given the current
antibiotic development pipeline it is likely that the paucity of therapeutic options will continue for the next years.
Colistin is an amphipathic bactericidal
antibiotic which is administered systemically as
colistin methanesulfonate (also known as
colistimethate sodium).
Colistin methanesulfonate is the inactive
prodrug, and in cerebrospinal fluid undergoes spontaneous hydrolysis to
colistin (the active form with antimicrobial activity). In this review, we describe and evaluate the clinical and experimental data supporting the use of intraventricular (IVT) or intrathecal (IT)
colistin against multidrug-resistant Gram-negative
infections of the central nervous system, describe the permeability of the blood-brain barrier to
colistin, the pharmacokinetics of
colistin after IVT administration of
colistin methanesulfonate, its anti-
endotoxin activity, discuss the opportunity to administer
colistin intraventricularly or intrathecally and the dose regimen, and provide recommendations based on the available evidence.