{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:38:13Z","timestamp":1792442293048,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"European Union\u2019s H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["861323"],"award-info":[{"award-number":["861323"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Temocillin is increasingly considered as an alternative to carbapenems. However, there is no consensus on optimal dosing strategies and limited data on temocillin efficacy in systemic infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We compared temocillin dosing strategies using pharmacokinetic\/pharmacodynamic (PK\/PD) modelling and simulation based on plasma exposure and in vitro time\u2013kill data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Temocillin effects on four Escherichia coli strains were evaluated using static time\u2013kill experiments and the hollow-fibre infection model, in which unbound plasma concentrations following intermittent and continuous infusion regimens of 4 and 6 g daily were replicated over 72 h. A PK\/PD model was developed to describe the time\u2013kill data. The PK\/PD model was coupled to a population PK model of temocillin in critically ill patients to predict bacterial killing and resistance development following various dosing regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Amplification of resistant subpopulations was observed within 24 h for all strains. The PK\/PD model described the observed bacterial kill kinetics and resistance development from both experimental systems well. Simulations indicated dose-dependent bacterial killing within and beyond the currently used daily dose range, and a superiority of continuous compared with intermittent infusions. However, regrowth of resistant subpopulations was frequently observed. For two strains, bacteriostasis over 72 h was predicted only with doses that are higher than those currently licensed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Continuous infusions and 6 g daily doses of temocillin kill E. coli more effectively than 4 g daily doses and intermittent infusions, and may increase efficacy in the treatment of systemic infections. However, higher daily doses may be required to suppress resistance development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae243","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T10:18:56Z","timestamp":1721470736000},"page":"2484-2492","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic\/pharmacodynamic model-based optimization of temocillin dosing strategies for the treatment of systemic infections"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-4173","authenticated-orcid":false,"given":"Wisse","family":"van Os","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna , Waehringer Guertel 18-20, 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-8488","authenticated-orcid":false,"given":"Alina","family":"Nussbaumer-Pr\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna , Waehringer Guertel 18-20, 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Duc","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Systems Pharmacology & Pharmacy, Leiden Academic Centre for Drug Research, Leiden University , Einsteinweg 55, 2333 CC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert-Jan","family":"Wijnant","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain , Avenue E. Mounier 73\/B1.73.05, 1200 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrin","family":"Ngougni Pokem","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain , Avenue E. Mounier 73\/B1.73.05, 1200 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-7991","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Van Bambeke","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain , Avenue E. 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