Pharmacokinetics of Ceftolozane-Tazobactam during Prolonged Intermittent Renal Replacement Therapy
- Authors
- 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.