Charalampos Antachopoulos (Greece)
Aristotle University of Thessaloniki 3rd Dept of PediatricsPresenter of 1 Presentation
POPULATION PHARMACOKINETICS OF INTRAVENOUS COLISTIN ADMINISTERED IN CRITICALLY ILL PEDIATRIC PATIENTS AT HIGHER THAN RECOMMENDED DOSES (ID 161)
Abstract
Background
A limited amount of pharmacokinetic (PK) data suggest that currently recommended pediatric dosages of colistimethate sodium (CMS) by the Food and Drug Administration and European Medicines Agency [75,000-150,000 IU/kg/day, equivalent to ~2.5-5 mg/kg/day of colistin base activity (CBA)] may lead to suboptimal exposure, resulting in plasma colistin concentrations frequently <2 mg/L.
Methods
We conducted a population PK study in critically ill patients 1 month-14 years old, who received CMS for infections caused by carbapenem-resistant Gram-negative bacteria. CMS was dosed at 200,000 IU/kg/day (6.6 mg CBA/kg/day), 300,000 IU/kg/day (9.9 mg CBA/kg/day) or 350,000 IU/kg/day (11.6 mg CBA/kg/day), according to patient age and severity of infection. Plasma colistin concentrations were determined using ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry. Patients were closely monitored for adverse events.
Results
A total of 17 patients, 3 months-13.75 years (median 3.3 years) old, were studied. Colistin PK was described by a one-compartment disposition model including creatinine clearance, body weight and the presence or absence of systemic inflammatory response syndrome (SIRS) as covariates. The average colistin plasma steady-state concentration (Css,avg) ranged from 1.11-8.47 mg/L (median 2.92 mg/L). Ten patients had Css,avg ≥2 mg/L. The presence of SIRS was associated with decreased apparent clearance of colistin (47.8% of that without SIRS). The relationship between the mg/day of CBA to achieve each 1 mg/L of plasma colistin Css,avg and creatinine clearance (mL/min) was described by linear regression with different slopes for patients with and without SIRS. Nephrotoxicity, probably colistin-unrelated, was observed in one patient.
Conclusions
Administration of CMS at the above doses improved exposure and was well tolerated. Apparent clearance of colistin was influenced by creatinine clearance and the presence or absence of SIRS.
Clinical Trial Registration
This study does not report the results of a controlled trial.