{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:56:59Z","timestamp":1787029019372,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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 (fCtrough\/MIC or fCss\/MIC) \u2265 1 or \u22654 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (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 fCtrough\/MIC or fCss\/MIC \u2265 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.<\/jats:p>","DOI":"10.3390\/microorganisms11122964","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T04:28:31Z","timestamp":1702355311000},"page":"2964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections"],"prefix":"10.3390","volume":"11","author":[{"given":"Pier Giorgio","family":"Cojutti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-4235","authenticated-orcid":false,"given":"Renato","family":"Pascale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-0394","authenticated-orcid":false,"given":"Jacopo","family":"Angelini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Santa Maria della Misericordia University Hospital of Udine, ASUFC, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Tascini","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":false,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1128\/AAC.02465-14","article-title":"Ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010","volume":"58","author":"Farrell","year":"2014","journal-title":"Antimicrob. 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