{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:55:15Z","timestamp":1777560915103,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021\u201331 March 2025. Desired isavuconazole exposure was defined as trough concentrations (Cmin) of 1.0\u20135.1 mg\/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole Cmin underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole Cmin was 3.5 mg\/L (2.1\u20134.6 mg\/L). Proportions of ECPAs with isavuconazole Cmin under- and overexposure were 4.2% (7\/166) and 16.3% (27\/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg\/m2; p &lt; 0.001). Trends of isavuconazole Cmin under- and overexposure changed over time, significantly decreasing the former (10.5% &lt;7 days vs. 4.3% 7\u201328 days vs. 0.0% &gt;28 days; p &lt; 0.001) and increasing the latter (5.3% &lt;7 days vs. 12.8% 7\u201328 days vs. 29.3% &gt;28 days; p &lt; 0.001). HTD occurred in 15\/32 patients, most of whom (10\/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment.<\/jats:p>","DOI":"10.3390\/antibiotics14080777","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:13:51Z","timestamp":1754475231000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TDM-Based Approach for Properly Managing Intravenous Isavuconazole Treatment in a Complex Case Mix of Critically Ill Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6856-8936","authenticated-orcid":false,"given":"Riccardo","family":"De Paola","sequence":"additional","affiliation":[{"name":"Specialisation School of Clinical Pharmacology and Toxicology, Alma Mater Studiorum Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-3595","authenticated-orcid":false,"given":"Tommaso","family":"Tonetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":false,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","first-page":"430","article-title":"Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients: Putting the Puzzle Together","volume":"25","author":"Blot","year":"2019","journal-title":"Curr. 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