Beschreibung:
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<jats:title>Background:</jats:title>
<jats:p>The antibacterial effect of antibiotics is linked to the free drug concentration. This study investigated the applicability of an ultrafiltration method to determine free plasma concentrations of beta-lactam antibiotics in ICU patients.</jats:p>
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<jats:title>Methods:</jats:title>
<jats:p>Eligible patients included adult ICU patients treated with ceftazidime (CAZ), meropenem (MEM), piperacillin (PIP)/tazobactam (TAZ), or flucloxacillin (FXN) by continuous infusion. Up to 2 arterial blood samples were drawn at steady state. Patients could be included more than once if they received another antibiotic. Free drug concentrations were determined by high-performance liquid chromatography with ultraviolet detection after ultrafiltration, using a method that maintained physiological conditions (pH 7.4/37°C). Total drug concentrations were determined to calculate the unbound fraction. In a post-hoc analysis, free concentrations were compared with the target value of 4× the epidemiological cut-off value (ECOFF) for <jats:italic toggle="yes">Pseudomonas aeruginosa</jats:italic> as a worst-case scenario for empirical therapy with CAZ, MEM or PIP/tazobactam and against methicillin-sensitive <jats:italic toggle="yes">Staphylococcus aureus</jats:italic> for targeted therapy with FXN.</jats:p>
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<jats:title>Results:</jats:title>
<jats:p>Fifty different antibiotic treatment periods in 38 patients were evaluated. The concentrations of the antibiotics showed a wide range because of the fixed dosing regimen in a mixed population with variable kidney function. The mean unbound fractions (<jats:italic toggle="yes">f</jats:italic>u) of CAZ, MEM, and PIP were 102.5%, 98.4%, and 95.7%, with interpatient variability of <6%. The mean <jats:italic toggle="yes">f</jats:italic>u of FXN was 11.6%, with interpatient variability of 39%. It was observed that 2 of 12 free concentrations of CAZ, 1 of 40 concentrations of MEM, and 11 of 23 concentrations of PIP were below the applied target concentration of 4 × ECOFF for <jats:italic toggle="yes">P. aeruginosa</jats:italic>. All concentrations of FXN (9 samples from 6 patients) were >8 × ECOFF for methicillin-sensitive <jats:italic toggle="yes">Staphylococcus aureus</jats:italic>.</jats:p>
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<jats:title>Conclusions:</jats:title>
<jats:p>For therapeutic drug monitoring purposes, measuring total or free concentrations of CAZ, MEM, or PIP is seemingly adequate. For highly protein-bound beta-lactams such as FXN, free concentrations should be favored in ICU patients with prevalent hypoalbuminemia.</jats:p>
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