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Optimizing the dosing regimen of linezolid in critically ill septic patients undergoing continuous hemodiafiltration using a pharmacokinetic/pharmacodynamic analysis and monte carlo simulation
© Barrasa González et al.; 2015
- Published: 1 October 2015
- Severe Sepsis
- Dose Regimen
- Monte Carlo Simulation
- Septic Patient
Pharmacokinetic (PK) of drugs in critically ill patients could vary from the general population. Patients undergoing hemodiafiltration (HDF) could present lower linezolid (LZ) concentration than expected. The pharmacokinetic/pharmacodynamic analysis (PK/ PD) is a useful tool to optimize dosing regimens of antibiotic therapy.
To evaluate the efficacy and safety of LZ for the treatment of infections caused by gram-positive microorganisms (GPM) in the Intensive Care Unit (ICU) patients undergoing HDF using a PK/PD analysis and Monte Carlo simulation (MCS).
Study developed in three tertiary hospitals in patients with severe sepsis, HDF and treatment with LZ (600mg q12h). 8 each patient blood (prefilter and postfilter) and ultrafiltrate samples were taken. Concentrations of linezolid were determined by HPLC-UV. PK analysis and MCS were performed using Phoenix WinNonlin Version 6.3 (Pharsight) and Oracle Crystal Ball programs to assess the probability of successful treatment (PST) [area under the curve (AUC24)/MIC> 100 for different MICs], the probability of Cmin>2 mg/L and the risk of overexposure (RO) [Cmin> 10 mg /L and/or AUC24> 400 mg * h/L] at doses of 600mg q12 and q8h. Patients were grouped by liver and renal function considering impaired liver function (ILF) the elevation> 2 times transaminase and/or elevated bilirubin and severe renal dysfunction (SRD) the presence of CrCl < 15 ml/min. Group (G) 0: both normal, G1: ILF or SRD, G2: both. Quantitative variables were expressed as mean and standard deviation (SD), qualitative as percentages. α significance level of 0,05.
In patients with RRT, 600 mg q12h guarantees PST >80% for MIC ≤1 in the presence of SRD and/or ILF. For this MIC, 600 mg q8h guarantees high PST in all patients and increases the probability of Cmin> 2. For MGP with MIC of 2, only in the presence of both dysfunctions is possible achieving the PK/PD target.
Pfizer sponsored this study.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.