Combined Intravenous and Intraventricular Administration of Colistin Methanesulfonate in Critically Ill Patients with Central Nervous System Infection

Colistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in criti-cally ill patients without central nervous system infection (controls, n 5) and in patients with external ventricular drain-asso-ciated ventriculitis after intravenous administration (EVDViv, n 3) or combined intravenous/intraventricular administration (EVDVcomb, n 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control pa-tients (11 % versus 7%, P< 0.05) and in EVDVcomb compared to all other patients (P< 0.0001). CSF colistin concentrations above theMIC of 0.5g/ml were achieved only in EVDVcomb patients. Previous studies have suggested that the level of antibiotics inthe ventricular cerebrospinal fluid (CSF) is important for the outcome of external ventricular drainage (EVD)-related ventric-ulitis (1–3). The presence of multiresistant bacteria and the poor penetration of many drugs through the blood-brain barrier have imposed the use of intrathecal therapies (4). Today, colistin, administered as its prodrug colistin methane-sulphonate (CMS), is one of the few antibiotics available for treat-ment of infections by multidrug-resistant Gram-negative organ-isms. However, intravenous (i.v.) administration is reported t