{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:50:54Z","timestamp":1792698654928,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"M.O., P.S. and K.M.R"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the \u03b2-lactam flucloxacillin are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We determined the achievement of pharmacokinetic\/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC\u2013MS, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In our study population, 48% were critically ill and the 30\u2009day mortality rate was 16%. The median flucloxacillin MIC was 0.125\u2009mg\/L. The median unbound trough concentration was 1.7 (IQR 0.4\u20139.3), 1.9 (IQR 0.4\u20136.2) and 1.0 (IQR 0.6\u20133.4) mg\/L on study day 1, 3 and 7, respectively. Optimal (100% fT&amp;gt;MIC) and maximum (100% fT&amp;gt;4\u00d7MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1\u2009mg\/L increase, P\u2009=\u20090.02) and significantly higher in deceased patients (median 14.8 versus 1.7\u2009mg\/L, P\u2009=\u20090.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab089","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T15:09:50Z","timestamp":1615475390000},"page":"1845-1854","source":"Crossref","is-referenced-by-count":29,"title":["Probability of pharmacological target attainment with flucloxacillin in\n                    <i>Staphylococcus aureus<\/i>\n                    bloodstream infection: a prospective cohort study of unbound plasma and individual MICs"],"prefix":"10.1093","volume":"76","author":[{"given":"Stephan","family":"Moser","sequence":"first","affiliation":[{"name":"Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-8319","authenticated-orcid":false,"given":"Sophia","family":"Rehm","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Guertler","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimira","family":"Hinic","sequence":"additional","affiliation":[{"name":"Division of Clinical Bacteriology and Mycology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dr\u00e4ger","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bassetti","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina M","family":"Rentsch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parham","family":"Sendi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"},{"name":"Institute for Infectious Diseases, University of Bern, Friedb\u00fchlstrasse 51, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Osthoff","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Schanzenstrasse 55, 4056, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"2021070808221056400_dkab089-B1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jinf.2013.10.015","article-title":"Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies","volume":"68","author":"Kaasch","year":"2014","journal-title":"J Infect"},{"key":"2021070808221056400_dkab089-B2","first-page":"263","article-title":"Bacteremia, sepsis, and infective endocarditis associated with Staphylococcus 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