Pulmonary and Systemic Pharmacokinetics of Colistin Following a Single Dose of Nebulized Colistimethate in Mechanically Ventilated Neonates

The purpose of this study was to evaluate the pulmonary and systemic pharmacokinetics of colistin following a single dose of nebulized colistimethate sodium (CMS) in mechanically ventilated neonates. We administered a single dose of nebulized CMS (approximately 120,000 IU/kg of CMS, equivalent to 4 mg/kg colistin base activity) to 6 ventilated neonates with ventilator-associated pneumonia. The median gestational age was 39 weeks (range, 32-39 weeks). Mean (+/- SD) tracheal aspirate colistin maximum concentration (C-max), area under the concentration-time curve (AUC(0-24)) and t(1/2) were 24.0 +/- 8.2 mu g/mL, 147.6 +/- 53.5 mu g center dot hours/mL and 9.8 +/- 5.5 hours, respectively. The plasma concentrations of colistin were low. In neonates, a single nebulized dose of CMS (120,000 IU) resulted in high local concentrations for at least 12 hours and low systemic concentrations of colistin. Twice daily nebulization might be more appropriate.