{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:01:58Z","timestamp":1791925318176,"version":"4.3.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["THC"],"published-print":{"date-parts":[[2022,3,11]]},"abstract":"<jats:p>BACKGROUND: Critically ill patients commonly suffer from infections that require antimicrobial therapy. In previous studies, liver dysfunction was shown to have an essential impact on the dose selection in these patients. This pilot study aims to assess the influence of liver dysfunction, measured by the novel LiMAx test, on clinical outcomes in critically ill patients treated with linezolid. METHODS: Twenty-nine critically ill patients were included and treated with linezolid. Indications for linezolid therapy were secondary or tertiary peritonitis (46.7%), bloodstream infection (6.7%) and 46.7% were other infections with gram-positive bacteria. Linezolid Cmin, maximal liver function capacity (LiMAx test) and plasma samples were collected while linezolid therapy was in a steady-state condition. Furthermore, potential factors for the clinical outcome were investigated using logistic regression analysis. Clinical cure was defined as the resolution or significant improvement of clinical symptoms without using additional antibiotic therapy or intervention. RESULTS: Cured patients presented lower median linezolid Cmin yet a significantly higher mean LiMAx-value compared to the clinical failure group (1.9 mg\/L vs. 5.1 mg\/L) (349 \u03bcg\/kg\/h vs. 131 \u03bcg\/kg\/h). In the logistic regression model, LiMAx &lt; 178 \u03bcg\/kg\/h was the only independent predictor of clinical failure with a sensitivity of 77% and specificity of 93%. CONCLUSIONS: The LiMAx test predicts clinical failure more precisely than linezolid trough levels in critically ill surgical patients. Therefore liver failure may have a stronger impact on the outcome of critically ill surgical patients than low linezolid Cmin. While linezolid Cmin failed to predict patient\u2019s outcome, LiMAx results were the only independent predictor of clinical failure.<\/jats:p>","DOI":"10.3233\/thc-191847","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T05:33:46Z","timestamp":1624685626000},"page":"309-321","source":"Crossref","is-referenced-by-count":6,"title":["Liver function, quantified by the LiMAx test, as a predictor for the clinical outcome of critically ill patients treated with linezolid"],"prefix":"10.1177","volume":"30","author":[{"given":"Rawan","family":"Alraish","sequence":"first","affiliation":[{"name":"Department of Surgery, Campus Charit\u00e9 Mitte\/Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian G.","family":"Wicha","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of 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Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes. BMC Infect Dis [Internet]. 2015 [cited 2018 Aug 1]; 15(1). 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