{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:55Z","timestamp":1787009035078,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Advanz Pharma Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Optimal antimicrobial drug exposure in the lung is required for ensuring successful treatment of community-acquired pneumonia (CAP). Little is known about the intrapulmonary pharmacokinetics (PK) of ceftobiprole when administered by continuous infusion (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the PK of high doses (3\u2005g\/day) CI of ceftobiprole in the plasma and epithelial lining fluid (ELF) in mechanically ventilated patients with CAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients receiving a CI of ceftobiprole (2.5\u2005g daily after a 0.5\u2005g bolus loading dose) for the treatment of severe CAP were eligible. Plasma and ELF samples were collected over 3 days of therapy. Concentrations were analysed by HPLC-UV, and population PK modelling was conducted using Monolix\u2122. Monte Carlo simulations were performed to estimate the probability of target attaining a free ELF concentration of 100% of time above MIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve patients, 2 female, median (IQR) age 67 (58\u201371), were enrolled with 108 plasma and 12 ELF concentrations included in the population analysis. The median (min\u2013max) lung penetration ratio was 30 (15\u201345) % after 3 doses of ceftobiprole. In the Monte Carlo simulations, higher doses given as CI (3\u2005g\/day) may be necessary for MICs up to 2\u2005mg\/L in patients with normal renal function. The final PK model using a 4\u200a\u00d7\u200aMIC plasma target may help to approximate ELF target attainment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The use of high doses of ceftobiprole given by CI may be necessary to achieve PK\/pharmacodynamic targets in ELF in critically ill patients with CAP and normal renal function, especially when less susceptible pathogen is suspected or identified.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf267","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:30:09Z","timestamp":1753183809000},"page":"2644-2653","source":"Crossref","is-referenced-by-count":2,"title":["Intrapulmonary concentrations of ceftobiprole high doses administered by continuous infusion in critically ill patients with community-acquired pneumonia"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-0034","authenticated-orcid":false,"given":"Claire","family":"Roger","sequence":"first","affiliation":[{"name":"Division of Anesthesia and Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, Univ Montpellier, N\u00eemes University Hospital , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Allaouchiche","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Lyon-Sud, Service de R\u00e9animation, Hospices Civils de Lyon , Pierre-B\u00e9nite 69310 ,","place":["France"]},{"name":"Universit\u00e9 Claude Bernard , Lyon 1, Lyon, France"},{"name":"Pulmonary and Cardiovascular Aggression in Sepsis APCSe, UPSP 2021.A101, Universit\u00e9 de Lyon, VetAgro Sup, Campus V\u00e9t\u00e9rinaire de Lyon , Marcy l'\u00c9toile F-69280 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Quint\u00e3o De Moraes","sequence":"additional","affiliation":[{"name":"ADLIN Science , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Ulrich Feudjio","sequence":"additional","affiliation":[{"name":"ADLIN Science , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob-Val\u00e9ry","family":"Occean","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Medical Statistics and Public Health, N\u00eemes University Hospital, Montpellier University , N\u00eemes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-2173","authenticated-orcid":false,"given":"Arnaud","family":"Friggeri","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Lyon-Sud, Service de R\u00e9animation, Hospices 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