Roger L Nation1, Samira M Garonzik2, Jian Li1, Visanu Thamlikitkul3, Evangelos J Giamarellos-Bourboulis4, David L Paterson5, John D Turnidge6, Alan Forrest2, Fernanda P Silveira7. 1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia. 2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York. 3. Division of Infectious Diseases and Tropical Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 4. 4th Department of Internal Medicine, University of Athens, Medical School, Greece. 5. University of Queensland Center for Clinical Research, Royal Brisbane and Women's Hospital, Australia. 6. Departments of Pathology and Paediatrics and School of Molecular and Biomedical Sciences, University of Adelaide, Australia. 7. Division of Infectious Diseases, University of Pittsburgh Medical Center, Pennsylvania.
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.
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 illpatients (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.
Authors: J Li; C R Rayner; R L Nation; R Deans; R Boots; N Widdecombe; A Douglas; J Lipman Journal: Antimicrob Agents Chemother Date: 2005-11 Impact factor: 5.191
Authors: Jian Li; Roger L Nation; John D Turnidge; Robert W Milne; Kingsley Coulthard; Craig R Rayner; David L Paterson Journal: Lancet Infect Dis Date: 2006-09 Impact factor: 25.071
Authors: Anand Kumar; Daniel Roberts; Kenneth E Wood; Bruce Light; Joseph E Parrillo; Satendra Sharma; Robert Suppes; Daniel Feinstein; Sergio Zanotti; Leo Taiberg; David Gurka; Aseem Kumar; Mary Cheang Journal: Crit Care Med Date: 2006-06 Impact factor: 7.598
Authors: Roger L Nation; Jian Li; Otto Cars; William Couet; Michael N Dudley; Keith S Kaye; Johan W Mouton; David L Paterson; Vincent H Tam; Ursula Theuretzbacher; Brian T Tsuji; John D Turnidge Journal: Lancet Infect Dis Date: 2014-10-21 Impact factor: 25.071
Authors: D Plachouras; M Karvanen; L E Friberg; E Papadomichelakis; A Antoniadou; I Tsangaris; I Karaiskos; G Poulakou; F Kontopidou; A Armaganidis; O Cars; H Giamarellou Journal: Antimicrob Agents Chemother Date: 2009-05-11 Impact factor: 5.191
Authors: Cornelia B Landersdorfer; Tri-Hung Nguyen; Linh Thuy Lieu; Gary Nguyen; Robert J Bischof; Els N Meeusen; Jian Li; Roger L Nation; Michelle P McIntosh Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191
Authors: Cornelia B Landersdorfer; Jiping Wang; Veronika Wirth; Ke Chen; Keith S Kaye; Brian T Tsuji; Jian Li; Roger L Nation Journal: J Antimicrob Chemother Date: 2018-02-01 Impact factor: 5.790
Authors: Roger L Nation; Samira M Garonzik; Visanu Thamlikitkul; Evangelos J Giamarellos-Bourboulis; Alan Forrest; David L Paterson; Jian Li; Fernanda P Silveira Journal: Clin Infect Dis Date: 2017-09-01 Impact factor: 9.079