Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections

Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effec...

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Bibliographic Details
Main Authors: Pier Giorgio Cojutti, Simone Giuliano, Renato Pascale, Jacopo Angelini, Carlo Tascini, Pierluigi Viale, Federico Pea
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/11/12/2964
Description
Summary:Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effect modeling. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) of free trough or steady-state concentration over MIC (<i>f</i>C<sub>trough</sub>/MIC or <i>f</i>C<sub>ss</sub>/MIC) ≥ 1 or ≥4 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>Staphylococcus epidermidis</i> (MRSE) were also calculated. A total of 132 patients with 503 concentrations were included. Most of them (107/132, 81.1%) had hospital- or community-acquired pneumonia, endocarditis, and bacteremia. A three-compartment model adequately fitted ceftobiprole concentration-time data. Estimated glomerular filtration rate significantly affected drug clearance. Monte Carlo simulations showed that the optimal target of <i>f</i>C<sub>trough</sub>/MIC or <i>f</i>C<sub>ss</sub>/MIC ≥ 4 is achieved only with the use of the standard dosages administered by continuous infusion (CI) against MRSA infections in patients with preserved renal function. Intensified dosages administered by CI are needed in patients with impaired renal function and/or augmented renal clearance against MRSA and in patients with preserved renal functions against MRSE.
ISSN:2076-2607