Higher Optimization of Pharmacokinetic and Pharmacodynamic Parameters Through Loading Dose of Intravenous Colistin in Pediatric Patients.

Colistin use in children is rising in accordance with the surge of multidrug-resistant Gram-negative bacteria (MDR-GNB). In adults, colistin loading dose is recommended to achieve the therapeutic level within 12-24 hours. We aimed to describe pharmacokinetic (PK) parameters of a loading dose versus a recommended initial dose of intravenous colistimethate sodium (CMS) in pediatric patients.A prospective, open-label, PK study was conducted in pediatric patients aged 2 - 18 years with normal renal function. Patients were randomly assigned to receive either CMS loading dose (LD group) of 4 mg of colistin base activity (CBA)/kg/dose or standard initial dose (NLD group) of 2.5 mg (12-h interval) or 1.7 mg (8-h interval) of CBA/kg/dose. Serial blood samples were collected. Plasma concentration of formed colistin was measured by LC-MS/MS method. PK parameters were reported. Acute kidney injury (AKI) was monitored by serum creatinine and urine NGAL.Twenty children were enrolled. The median (interquartile range) age and body weight were 8.5 years (3.5-11.3) and 21.5 kg (13.5-20.0). The mean (standard deviation) of first-dose PK parameters of the LD group vs the NLD group were C 6.1 (2.4) vs 4.1 (1.3) mg/L, AUC 26.5 (12.5) vs 13.5 (3.6) mg/L*h, Vd 0.7 (0.4) vs 0.6 (0.3) L/kg, and t 2.9 (0.6) vs 2.6 (0.4) h. There was no patient developed AKI by serum creatinine criteria.CMS loading dose is beneficial for the improvement of colistin exposure without increased AKI. A higher daily dose of CMS should be considered especially for MDR-GNB treatment.