Updated US and European dose recommendations for intravenous colistin: how do they perform?

Nation, Roger L., Garonzik, Samira M., Li, Jian, Thamlikitkul, Visanu, Giamarellos-Bourboulis, Evangelos J., Paterson, David L., Turnidge, John D., Forrest, Alan and Silveira, Fernanda P. (2016) Updated US and European dose recommendations for intravenous colistin: how do they perform?. Clinical Infectious Diseases, 62 5: 552-558. doi:10.1093/cid/civ964


Author Nation, Roger L.
Garonzik, Samira M.
Li, Jian
Thamlikitkul, Visanu
Giamarellos-Bourboulis, Evangelos J.
Paterson, David L.
Turnidge, John D.
Forrest, Alan
Silveira, Fernanda P.
Title Updated US and European dose recommendations for intravenous colistin: how do they perform?
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1537-6591
1058-4838
Publication date 2016-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1093/cid/civ964
Open Access Status Not Open Access
Volume 62
Issue 5
Start page 552
End page 558
Total pages 7
Place of publication Cary, NC United States
Publisher Oxford University Press
Language eng
Formatted abstract
Background. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved updated dose recommendations for intravenous colistin in patients with various degrees of renal function. We assessed the recommendations in relation to their ability to achieve clinically relevant plasma colistin concentrations.

Methods. Pharmacokinetic data from 162 adult critically ill patients (creatinine clearance range, 5.4–211 mL/min) were used to determine the average steady-state plasma colistin concentration (Css,avg) that would be achieved if each patient received the FDA or EMA dose. Target attainment rates for FDA- and EMA-approved daily doses to achieve colistin Css,avg of ≥0.5, ≥1, ≥2, and ≥4 mg/L were determined for each creatinine clearance category (≥80 mL/min, 50 to <80 mL/min, 30 to <50 mL/min, and <30 mL/min).

Results. For creatinine clearance <30 mL/min, 100% of patients receiving the EMA dose achieved a colistin Css,avg ≥1 mg/L, but the attainment rate was as low as 53.1% for patients receiving the FDA-approved dose. For colistin Css,avg ≥2 mg/L, the attainment rates were 87.5% with the EMA dose but only 6.3%–34.4% in patients receiving the FDA dose. Differences in attainment rates for a colistin Css,avg of ≥2 mg/L and ≥4 mg/L extended to patients with creatinine clearance 30 to <50 mL/min. For patients with creatinine clearance ≥80 mL/min, only approximately 65%–75% of patients achieved a colistin Css,avg of ≥1 mg/L with either set of recommendations.

Conclusions. The study highlights important differences between the FDA- and EMA-approved dose recommendations and informs the setting of clinical breakpoints.

Clinical Trials Registration. NCT00235690.
Keyword Intravenous colistin
Updated FDA-and EMA-approved dosing suggestions
Plasma colistin concentrations achieved
Clinical breakpoints
Therapeutic implications
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
 
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