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Pharmacokinetics of Ceftolozane-Tazobactam during Prolonged Intermittent Renal Replacement Therapy

Authors
  • Rawlins, Matthew
  • Cheng, Vesa
  • Raby, Edward
  • Dyer, John
  • Regli, Adrian
  • Ingram, Paul
  • McWhinney, Brett C.
  • Ungerer, Jacobus P.J.
  • Roberts, Jason A.
Type
Published Article
Journal
Chemotherapy
Publisher
S. Karger AG
Publication Date
Oct 10, 2018
Volume
63
Issue
4
Pages
203–206
Identifiers
DOI: 10.1159/000493196
PMID: 30304718
Source
Karger
Keywords
License
Green
External links

Abstract

Background: Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely. Objectives: Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad­ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa. Method: Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model. Results: Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively). Conclusions: A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer’s recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.

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