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Extended or continuous regimens are often used to improve target attainment. Although prompt antibiotic initiation is a major determinant of survival, few studies have reported systemic concentrations early after treatment initiation. No prior study has reported concentrations immediately after the loading dose and first extended infusion. This study aimed to evaluate plasma target attainment during the first dosing interval with an extended infusion regimen in a general intensive care unit (ICU).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Adult ICU patients were prospectively included in conjunction with the first administration of meropenem or piperacillin-tazobactam. Treatment was initiated with a 0.5\u00a0h loading dose immediately followed by a 3\u00a0h extended infusion; typically 4\u2009+\u20094\u00a0g piperacillin or 1(\u2212\u20092)g\u2009+\u20091(\u2212\u20092)g meropenem, in line with the local ICU protocol. Patients requiring renal replacement therapy were excluded. Plasma concentrations were measured post-loading dose (C<jats:sub>max<\/jats:sub>), near the end of the first extended infusion, and at the end of the first dosing interval (C<jats:sub>min<\/jats:sub>). Samples were analyzed using validated tandem mass spectrometry (UHPLC-MS\/MS) methods. The primary endpoint was the proportion of patients achieving 100% time above minimum inhibitory concentrations (<jats:italic>f<\/jats:italic>T\u2009&gt;\u2009MIC) during the first dosing interval. This was evaluated using observed C<jats:sub>min<\/jats:sub> above 2\u00a0mg\/L (meropenem) and 20\u00a0mg\/L (piperacillin). Additionally, published pharmacokinetic models were applied to the observed data for %fT\u2009&gt;\u2009MIC estimation, using an a posteriori Bayesian approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We included 65 meropenem and 142 piperacillin measurements from 22 and 48 patients, respectively. Many patients (45% meropenem, 38% piperacillin) failed to reach 100% <jats:italic>f<\/jats:italic>T\u2009&gt;\u2009MIC with the standard regimens used. Target non-attainment was associated with high estimated glomerular filtration rates (eGFR) and suspected augmented renal clearance (ARC). All meropenem patients that failed to reach target had eGFR\u2009&gt;\u200990\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>, as did 76% of corresponding piperacillin patients. Patients with suspected ARC frequently exhibited a tenfold or greater peak-to-trough decline (C<jats:sub>min<\/jats:sub>\/C<jats:sub>max<\/jats:sub>\u2009&lt;\u20090.1). <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Despite aggressive dosing, plasma concentrations often fail to reach 100% <jats:italic>f<\/jats:italic>T\u2009&gt;\u2009MIC during the first dosing interval. Alternative regimens and early plasma concentration measurements followed by adaptive dose adjustments should be considered to improve target attainment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13054-025-05445-0","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:35:25Z","timestamp":1747910125000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["First dose target attainment with extended infusion regimens of piperacillin and meropenem"],"prefix":"10.1186","volume":"29","author":[{"given":"Gustaf","family":"Beijer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Swartling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet I.","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian G.","family":"Giske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Eliasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Petersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"issue":"1","key":"5445_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/516284","volume":"26","author":"WA Craig","year":"1998","unstructured":"Craig WA. 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Informed consent to study participation was obtained from patients before blood sampling if possible, or after blood sampling but before data analysis (with assent from the closest relatives) when necessary due to altered consciousness, in accordance with the ethical approval and the Swedish Ethical Review Act (SFS 2003:460).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"208"}}