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Challenge for higher colistin dosage in critically ill patients receiving continuous venovenous haemodiafiltration
Hygeia Gen Hosp, Dept Internal Med 6, Athens, Greece.;Hygeia Gen Hosp, 4 Erythrou Stavrou Str & Kifisias, Athens 15123, Greece..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Hygeia Gen Hosp, Dept Internal Med 6, Athens, Greece..
Hygeia Gen Hosp, 4 Erythrou Stavrou Str & Kifisias, Athens 15123, Greece..
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2016 (English)In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 48, no 3, 337-341 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 48, no 3, 337-341 p.
Keyword [en]
Colistin, CMS, Loading dose, Pharmacokinetics, CVHHDF
National Category
Pharmaceutical Sciences Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-308782DOI: 10.1016/j.ijantimicag.2016.06.008ISI: 000386022000018PubMedID: 27474468OAI: oai:DiVA.org:uu-308782DiVA: diva2:1054601
Available from: 2016-12-08 Created: 2016-11-30 Last updated: 2016-12-08Bibliographically approved

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