A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration.
Acute Kidney Injury
/ drug therapy
Anti-Bacterial Agents
/ administration & dosage
Cephalosporins
/ administration & dosage
Confidence Intervals
Continuous Renal Replacement Therapy
Critical Illness
Hemodiafiltration
/ methods
Humans
Microbial Sensitivity Tests
Prospective Studies
Pseudomonas aeruginosa
/ drug effects
Tazobactam
/ administration & dosage
CRRT
ceftolozane-tazobactam
hemodiafiltration
pharmacokinetics
renal replacement therapy
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:
20 12 2019
20 12 2019
Historique:
received:
15
08
2019
accepted:
15
10
2019
pubmed:
30
10
2019
medline:
1
9
2020
entrez:
30
10
2019
Statut:
epublish
Résumé
The aim of this work was to describe optimized dosing regimens of ceftolozane-tazobactam for critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF). We conducted a prospective observational pharmacokinetic study in adult critically ill patients with clinical indications for ceftolozane-tazobactam and CVVHDF. Unbound drug concentrations were measured from serial prefilter blood, postfilter blood, and ultrafiltrate samples by a chromatographic assay. Population pharmacokinetic modeling and dosing simulations were performed using Pmetrics. A four-compartment pharmacokinetic model adequately described the data from six patients. The mean (± standard deviation [SD]) extraction ratios for ceftolozane and tazobactam were 0.76 ± 0.08 and 0.73 ± 0.1, respectively. The mean ± SD sieving coefficients were 0.94 ± 0.24 and 1.08 ± 0.30, respectively. Model-estimated CVVHDF clearance rates were 2.7 ± 0.8 and 3.0 ± 0.6 liters/h, respectively. Residual non-CVVHDF clearance rates were 0.6 ± 0.5 and 3.3 ± 0.9 liters/h, respectively. In the initial 24 h, doses as low as 0.75 g every 8 h enabled cumulative fractional response of ≥85% for empirical coverage against
Identifiants
pubmed: 31658965
pii: AAC.01655-19
doi: 10.1128/AAC.01655-19
pmc: PMC7187594
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cephalosporins
0
ceftolozane, tazobactam drug combination
0
Tazobactam
SE10G96M8W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 Sime et al.
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