title: Challenge for higher colistin dosage in critically ill patients receiving continuous venovenous haemodiafiltration.
abstract: Traditionally, reduced daily doses of colistin methanesulphonate (CMS) in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF) have resulted in suboptimal colistin concentrations. The necessity of a loading dose (LD) at treatment initiation has been proposed. A LD of 9 million IU (MU) [ca. 270 mg of colistin base activity (CBA)] was administrated with a maintenance dose of 4.5 MU (ca. 140 mg CBA) every 12 h (q12h) to eight critically ill patients receiving renal replacement therapy. Blood samples were collected immediately before and at different time intervals after the LD and the fourth dose, whilst pre-filter and post-filter blood samples were also collected. CMS and colistin concentrations were determined using an LC-MS/MS assay. Median maximum observed concentrations after the LD were 22.1 mg/L for CMS and 1.55 mg/L for colistin, whereas during maintenance dosing the corresponding values were 12.6 mg/L and 1.72 mg/L, respectively. CVVHDF clearance was determined as 2.98 L/h for colistin, equivalent to 62% of total apparent colistin clearance in CVVHDF patients. Both CMS and colistin were cleared by CVVHDF. Application of a LD of 9 MU CMS resulted in more rapid achievement of the target colistin concentration. Following implementation of a predicted pharmacokinetic model on plasma CMS/colistin concentrations, a LD of 12 MU CMS appears more appropriate, whilst a CMS maintenance dosage of at least 6.5-7.5 MU q12h is suggested in patients undergoing CVVHDF. However, further clinical studies are warranted to assess the safety of a LD of 12 MU CMS in patients receiving CVVHDF.
authors.affiliation: 6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece. Electronic address: ikaraiskos@hygeia.gr.
authors.forename: Ilias
authors.initials: I
authors.lastname: Karaiskos
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.affiliation: 6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
authors.forename: Lambrini
authors.initials: L
authors.lastname: Galani
authors.affiliation: Clinical Pharmacist, Hygeia General Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ioannidis
authors.affiliation: Intensive Care Unit, Hygeia General Hospital, Athens, Greece.
authors.forename: Emmanouela
authors.initials: E
authors.lastname: Katsouda
authors.affiliation: Intensive Care Unit, Hygeia General Hospital, Athens, Greece.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Athanassa
authors.affiliation: Intensive Care Unit, Hygeia General Hospital, Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Paskalis
authors.affiliation: 6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003091:Colistin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010949:Plasma / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: CMS; CVHHDF; Colistin; Loading dose; Pharmacokinetics