Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy.
Adult
Aged
Anti-Bacterial Agents
/ pharmacokinetics
Chromatography, Liquid
Colistin
/ analogs & derivatives
Continuous Renal Replacement Therapy
/ methods
Escherichia coli
/ drug effects
Escherichia coli Infections
/ drug therapy
Female
Humans
Male
Mass Spectrometry
Middle Aged
Prospective Studies
Pseudomonas Infections
/ drug therapy
Pseudomonas aeruginosa
/ drug effects
colistimethate sodim
colistin
continuous renal replacement therapy
hemodiafiltration
population pharmacokinetics
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
27
09
2018
accepted:
12
11
2018
pubmed:
28
11
2018
medline:
6
2
2020
entrez:
28
11
2018
Statut:
epublish
Résumé
Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).
Identifiants
pubmed: 30478168
pii: AAC.01957-18
doi: 10.1128/AAC.01957-18
pmc: PMC6355613
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
colistinmethanesulfonic acid
DL2R53P963
Colistin
Z67X93HJG1
Banques de données
ClinicalTrials.gov
['NCT02081560']
Types de publication
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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