TY - JOUR
T1 - Updated US and European Dose Recommendations for Intravenous Colistin
T2 - How Do They Perform?
AU - Nation, Roger L
AU - Garonzik, Samira M.
AU - Li, Jian
AU - Thamlikitkul, Visanu
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Paterson, David L
AU - Turnidge, John D.
AU - Forrest, Alan
AU - Silveira, Fernanda P.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Clinical breakpoints
KW - Intravenous colistin
KW - Plasma colistin concentrations achieved
KW - Therapeutic implications
KW - Updated FDA-and EMA-approved dosing suggestions
UR - http://www.scopus.com/inward/record.url?scp=84960191949&partnerID=8YFLogxK
U2 - 10.1093/cid/civ964
DO - 10.1093/cid/civ964
M3 - Article
AN - SCOPUS:84960191949
SN - 1058-4838
VL - 62
SP - 552
EP - 558
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -
