{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:02:25Z","timestamp":1792245745871,"version":"4.4.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"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>Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials\/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2\u201310 mg\/L, but was adjusted to 2\u20135 mg\/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg\/L (0.5\u201315.4 mg\/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg\/L (0.2\u201321.9 mg\/L) with 67% of measurements within the therapeutic index. The median intra-\/interindividual coefficient of variation (CV) was 43.4%\/54.8% for ISZ compared to 53.2%\/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug\u2013drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra\/interindividual CV than patients receiving VRZ.<\/jats:p>","DOI":"10.3390\/antibiotics10050487","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T12:08:30Z","timestamp":1619179710000},"page":"487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole"],"prefix":"10.3390","volume":"10","author":[{"given":"Malene","family":"Risum","sequence":"first","affiliation":[{"name":"Unit of Mycology, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark"},{"name":"Department of Haematology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai-Britt","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla M\u00f8ller","family":"Weinreich","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"The Clinical Institute, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2370-1657","authenticated-orcid":false,"given":"Marie","family":"Helleberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja Hawwa","family":"Vissing","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-466X","authenticated-orcid":false,"given":"Ren\u00e9","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Unit of Mycology, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global guideline for the diag-nosis and management of mucormycosis: An initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium","volume":"19","author":"Cornely","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2147\/IDR.S51340","article-title":"Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections","volume":"6","author":"Pasqualotto","year":"2013","journal-title":"Infect. Drug Resist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/cid\/civ571","article-title":"Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent","volume":"61","author":"Miceli","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S1473-3099(16)00071-2","article-title":"Isavuconazole treatment for mucormycosis: A single-arm open-label trial and case-control analysis","volume":"16","author":"Marty","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): A phase 3, ran-domised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1093\/cid\/ciy827","article-title":"Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial","volume":"68","author":"Kullberg","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","unstructured":"Bose, P., McCue, D., Wurster, S., Wiederhold, N.P., Konopleva, M., Kadia, T.M., Borthakur, G., Ravandi, F., Masarova, L., and Takahashi, K. (2020). Isavuconazole as Primary Anti-Fungal Prophy-laxis in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome: An Open-Label, Prospective, Phase II Study. Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.bbmt.2020.02.009","article-title":"A Single-Center, Open-Label Trial of Isavuconazole Prophylaxis against Invasive Fungal Infection in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: Isavuconazole for Antifungal Prophylaxis following HCT","volume":"26","author":"Stern","year":"2020","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/cid\/ciz282","article-title":"Isavuconazole Prophylaxis in Patients With Hematologic Malignancies and Hematopoietic Cell Transplant Recipients","volume":"70","author":"Fontana","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vu, C.A., Rana, M.M., Jacobs, S.E., and Saunders-Hao, P. (2020). Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience. Transpl. Infect. Dis., e13469.","DOI":"10.1111\/tid.13469"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Samanta, P., Clancy, C.J., Marini, R.V., Rivosecchi, R.M., McCreary, E.K., Shields, R.K., Falcione, B.A., Viehman, A., Sacha, L., and Kwak, E.J. (2020). Isavuconazole Is as Effective as and Bet-ter Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients. Clin. Infect Dis.","DOI":"10.1093\/cid\/ciaa652"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Decembrino, N., Perruccio, K., Zecca, M., Colombini, A., Calore, E., Muggeo, P., Soncini, E., Comelli, A., Molinaro, M., and Goffredo, B.M. (2019). A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.01783-19"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/myc.12885","article-title":"Isavuconazole and voriconazole for the treatment of chronic pulmonary aspergillosis: A retrospective comparison of rates of adverse events","volume":"62","author":"Bongomin","year":"2018","journal-title":"Mycoses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e01511-20","DOI":"10.1128\/AAC.01511-20","article-title":"Isavuconazole therapeutic drug monitoring dur-ing long-term treatment for chronic pulmonary aspergillosis","volume":"65","author":"Kosmidis","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S328","DOI":"10.1093\/mmy\/myz012","article-title":"Antifungal drugs: What brings the future?","volume":"57","author":"Spriet","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e01034-17","DOI":"10.1128\/AAC.01034-17","article-title":"Exposure-response relationships for isavuconazole in patients with invasive aspergillosis and other filamentous fungi","volume":"61","author":"Desai","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1093\/jac\/dkz188","article-title":"Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy","volume":"74","author":"Furfaro","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","unstructured":"Statens Serum Institut (2021, March 01). Voriconazole (Serumconcentration). Available online: https:\/\/www.ssi.dk\/produkter-og-ydelser\/diagnostik."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00098-17","DOI":"10.1128\/mSphere.00098-17","article-title":"Implementation of isavuconazole in a fluorescence-based highper-formance liquid chromatography kit allowing simultaneous detection of all four currently licensed mold-active triazoles","volume":"2","author":"Andersen","year":"2017","journal-title":"Msphere"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Risum, M., Helweg-Larsen, J., Petersen, S.L., Kampmann, P., Overgaard, U.M., El Fassi, D., Nielsen, O.J., Brabrand, M., Rubek, N., and Munksgaard, L. (2020). Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis: A Pre and Post-Intervention Analysis. J. Fungi, 6.","DOI":"10.3390\/jof6040268"},{"key":"ref_21","unstructured":"J\u00f8rgensen, R., Risum, M., and Arendrup, M.C. (2020, January 18\u201321). Therapeutic drug monitoring of isavuconazole in patients undergoing antifungal treatment in Denmark. Proceedings of the 30th European Congress of Clinical Microbiology and Infectious Diseases, Paris, France."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the My-coses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/jac\/dky463","article-title":"Variability and exposure\u2013response relationships of isavuconazole plasma concentrations in the Phase 3 SECURE trial of patients with invasive mould diseases","volume":"74","author":"Kaindl","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00585-18","DOI":"10.1128\/AAC.00585-18","article-title":"Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials","volume":"62","author":"Andes","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zurl, C., Waller, M., Schwameis, F., Muhr, T., Bauer, N., Zollner-Schwetz, I., Valentin, T., Meinitzer, A., Ullrich, E., and Wunsch, S. (2020). Isavuconazole treatment in a mixed patient co-hort with invasive fungal infections: Outcome, tolerability and clinical implications of isavuconazole plasma concentra-tions. J. Fungi, 6.","DOI":"10.3390\/jof6020090"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/mmy\/myaa022","article-title":"Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center","volume":"58","author":"Borman","year":"2020","journal-title":"Med. Mycol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.01245-19","article-title":"Impact of Triazole Therapeutic Drug Monitoring Availability and Timing","volume":"63","author":"McCreary","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","first-page":"1","article-title":"Treatment by Posaconazole Tablets, Compared to Posaconazole Suspension, Does Not Reduce Variability of Posaconazole Trough Concentrations","volume":"63","author":"Bolcato","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mmcr.2018.07.006","article-title":"Late-onset isavuconazole-induced liver injury","volume":"22","author":"Bongomin","year":"2018","journal-title":"Med. Mycol. Case Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1093\/ofid\/ofx163.028","article-title":"Real-World Use\u2014Isavuconazole at a Large Academic Medical Center","volume":"4","author":"Hassouna","year":"2017","journal-title":"Open Forum Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e320","DOI":"10.1097\/HS9.0000000000000320","article-title":"Isavuconazole in Hematological Patients: Results of a Real-Life Multicentre Observational Seifem Study","volume":"3","author":"Cattaneo","year":"2019","journal-title":"HemaSphere"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1093\/cid\/ciy260","article-title":"Breakthrough Invasive Fungal Infections on Isavuconazole Prophylaxis and Treatment: What Is Happening in the Real-World Setting?","volume":"67","author":"Fung","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","first-page":"1610","article-title":"Breakthrough Fungal Infections in Patients with Leukemia Receiving Isavuconazole","volume":"67","author":"Rausch","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jac\/dkx423","article-title":"Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: A post hoc analysis of the SECURE trial","volume":"73","author":"Kontoyiannis","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/cpdd.284","article-title":"Pharmacokinetic Assessment of Drug-Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults","volume":"6","author":"Groll","year":"2016","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13007","DOI":"10.1111\/tid.13007","article-title":"Effect of isavuconazole on tacrolimus and sirolimus serum concentra-tions in allogeneic hematopoietic stem cell transplant patients: A drug-drug interaction study","volume":"21","author":"Kieu","year":"2019","journal-title":"Transpl. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/myc.12778","article-title":"Isavuconazole for treatment of rare invasive fungal diseases","volume":"61","author":"Cornely","year":"2018","journal-title":"Mycoses"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1128\/AAC.04569-14","article-title":"Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study","volume":"59","author":"Cornely","year":"2015","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:40Z","timestamp":1760161900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["antibiotics10050487"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10050487","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}