{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:05:02Z","timestamp":1793862302485,"version":"4.6.1"},"reference-count":105,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)\u2014Brazil"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with leukemia are at heightened risk for invasive fungal infections (IFIs) due to profound immunosuppression caused by both the malignancy and its treatment. Chemotherapy-induced neutropenia, mucosal barrier disruption, and impaired innate and adaptive immune responses create a highly permissive environment for opportunistic fungal pathogens. Antifungal prophylaxis, particularly in acute myeloid leukemia (AML), has become a cornerstone in reducing IFI-related morbidity and mortality. This review outlines the immunopathogenic mechanisms underlying susceptibility to IFI and discusses current evidence on the optimal timing and therapeutic strategies for antifungal intervention. The clinical utility of key antifungal agents, namely, posaconazole, isavuconazole, and voriconazole, is critically evaluated. We also examine the potential role of emerging agents such as opelconazole, which enables targeted pulmonary delivery and prolonged epithelial retention, representing a promising approach to IFI prevention. Drug-specific considerations, including pharmacokinetics, drug\u2013drug interactions, toxicity profiles, and cost-effectiveness, are analyzed in the context of clinical decision-making. Finally, we emphasize the importance of tailoring antifungal strategies based on leukemia subtype, immunosuppressive status, and individual patient factors to optimize outcomes and support antifungal stewardship in hematologic malignancies.<\/jats:p>","DOI":"10.3390\/ijms27020817","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Emerging Applications of Triazole Antifungal Drugs"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9172-9320","authenticated-orcid":false,"given":"Luiz Ricardo","family":"Soldi","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-1700","authenticated-orcid":false,"given":"Ana Paula de Lima","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Faculty of Odontology, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38405-318, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-4286","authenticated-orcid":false,"given":"Marcelo Jos\u00e9 Barbosa","family":"Silva","sequence":"additional","affiliation":[{"name":"Tumor Biomarkers and Osteoimmunology Laboratory, Av. Par\u00e1, 1720, Block 6T, Room 07, District Umuarama, Uberl\u00e2ndia 38400-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1086\/649879","article-title":"Fungal infections in leukemia patients: How do we prevent and treat them?","volume":"50","author":"Leventakos","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/ajh.25808","article-title":"Risk of invasive fungal infections in patients with high-risk MDS and AML receiving hypomethylating agents","volume":"95","author":"Kim","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S1085-5629(97)80043-0","article-title":"Fungal infections in HIV-infected patients","volume":"16","author":"Durden","year":"1997","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1182\/asheducation-2003.1.438","article-title":"Infections in patients with hematological cancer: Recent developments","volume":"2003","author":"Blijlevens","year":"2003","journal-title":"Hematology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14575","DOI":"10.1038\/s41598-020-71571-0","article-title":"Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: A systematic review with meta-analysis and trial sequential analysis","volume":"10","author":"Wong","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/MPH.0000000000002723","article-title":"Invasive fungal infections in children with acute myeloid leukemia: A single-center experience over 19 years","volume":"45","author":"Avcu","year":"2023","journal-title":"J. Pediatr. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e39959","DOI":"10.1097\/MD.0000000000039959","article-title":"Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital","volume":"103","author":"Alkan","year":"2024","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hassoun, N., Kassem, I.I., Hamze, M., El Tom, J., Papon, N., and Osman, M. (2023). Antifungal use and resistance in a lower\u2013middle-income country: The case of Lebanon. Antibiotics, 12.","DOI":"10.3390\/antibiotics12091413"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sienkiewicz-Oleszkiewicz, B., Salamonowicz-Bodzioch, M., S\u0142onka, J., and Ka\u0142wak, K. (2023). Antifungal drug-drug interactions with commonly used pharmaceutics in european pediatric patients with acute lymphoblastic leukemia. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144637"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S118892","article-title":"Fluconazole resistance in Candida species: A current perspective","volume":"10","author":"Berkow","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wall, G., and Lopez-Ribot, J.L. (2020). Current antimycotics, new prospects, and future approaches to antifungal therapy. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080445"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1128\/IAI.01172-13","article-title":"Eosinophil deficiency compromises lung defense against Aspergillus fumigatus","volume":"82","author":"Lilly","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41590-019-0377-2","article-title":"CARD9+ microglia promote antifungal immunity via IL-1\u03b2- and CXCL1-mediated neutrophil recruitment","volume":"20","author":"Drummond","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"660","DOI":"10.4049\/jimmunol.2100495","article-title":"IL-33 coordinates innate defense to systemic Candida albicans infection by regulating IL-23 and IL-10 in an opposite Way","volume":"208","author":"Nguyen","year":"2022","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Burgess, T.B., Condliffe, A.M., and Elks, P.M. (2022). A Fun-Guide to Innate Immune Responses to Fungal Infections. J. Fungi, 8.","DOI":"10.3390\/jof8080805"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a019612","DOI":"10.1101\/cshperspect.a019612","article-title":"Adaptive immunity to fungi","volume":"5","author":"Verma","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Teoh, F., and Pavelka, N. (2016). How chemotherapy increases the risk of systemic candidiasis in cancer patients: Current paradigm and future directions. Pathogens, 5.","DOI":"10.3390\/pathogens5010006"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"835","DOI":"10.21037\/hbsn-22-438","article-title":"Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation","volume":"12","author":"Qin","year":"2023","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Schmidt, S., Schubert, R., Demir, A., and Lehrnbecher, T. (2019). Distinct effects of immunosuppressive drugs on the anti-aspergillus activity of human natural killer cells. Pathogens, 8.","DOI":"10.3390\/pathogens8040246"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Arruga, F., Iannello, A., Deaglio, S., Vitale, N., Vaisitti, T., and Gyau, B.B. (2020). Immune response dysfunction in chronic lymphocytic leukemia: Dissecting molecular mechanisms and microenvironmental conditions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051825"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ersvaer, E., Brenner, A.K., Vet\u00e5s, K., Reikvam, H., and Bruserud, \u00d8. (2015). Effects of cytarabine on activation of human T cells\u2014Cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid. BMC Pharmacol. Toxicol., 16.","DOI":"10.1186\/s40360-015-0012-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/QCO.0b013e328348b159","article-title":"Immune responses against Aspergillus fumigatus: What have we learned?","volume":"24","author":"Cramer","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/SPC.0000000000000292","article-title":"Persistent pain in cancer survivors","volume":"11","author":"Boland","year":"2017","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/cncr.23448","article-title":"Physical and psychological long-term and late effects of cancer","volume":"112","author":"Stein","year":"2008","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dagher, H., Shah, S., Raad, I., Chaftari, A.M., Jiang, Y., Ali, S., Hachem, R., and Deeba, R. (2022). Real-world Use of isavuconazole as primary therapy for invasive fungal infections in high-risk patients with hematologic malignancy or stem Cell transplant. J. Fungi, 8.","DOI":"10.3390\/jof8010074"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-3062.2006.00123.x","article-title":"Empiric versus preemptive therapy in the management of febrile neutropenia in the patient being treated for hematologic malignancy","volume":"8","author":"Rubin","year":"2006","journal-title":"Transpl. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fung, M., Schwarzinger, M., Kim, J., Koo, S., and Marty, F.M. (2015). Meta-analysis and Cost comparison of empirical versus pre-emptive antifungal strategies in hematologic malignancy patients with high-risk febrile neutropenia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140930"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1086\/597395","article-title":"Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: A randomized, controlled trial","volume":"48","author":"Cordonnier","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1473-3099(13)70076-8","article-title":"Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: A randomised controlled trial","volume":"13","author":"Morrissey","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global guideline for the diagnosis 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_32","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1038\/s41467-024-48029-2","article-title":"A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1","volume":"15","author":"Rybak","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ijantimicag.2015.02.023","article-title":"Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid leukaemia: Efficacy and cost effectiveness in real-life","volume":"46","author":"Chong","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rahi, M.S., Jindal, V., Pednekar, P., Parekh, J., Gunasekaran, K., Sharma, S., Stender, M., and Jaiyesimi, I.A. (2021). Fungal infections in hematopoietic stem-cell transplant patients: A review of epidemiology, diagnosis, and management. Ther. Adv. Infect. Dis., 8.","DOI":"10.1177\/20499361211039050"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.12659\/MSM.893142","article-title":"Clinical analysis of adverse drug reactions between vincristine and triazoles in children with acute lymphoblastic leukemia","volume":"21","author":"Yang","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ismail, M., Khan, S., Khan, F., Noor, S., Sajid, H., Yar, S., and Rasheed, I. (2020). Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06855-9"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104405","DOI":"10.1016\/j.critrevonc.2024.104405","article-title":"Clinical implications of the drug-Drug interaction in cancer patients treated with innovative oncological treatments","volume":"200","author":"Santamaria","year":"2024","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101190","DOI":"10.1016\/j.mam.2023.101190","article-title":"Antifungal prophylaxis and pre-emptive therapy: When and how?","volume":"92","author":"Sprute","year":"2023","journal-title":"Mol. Asp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s40265-020-01306-y","article-title":"Pharmacokinetics and pharmacodynamics of posaconazole","volume":"80","author":"Chen","year":"2020","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/14656566.2021.1996562","article-title":"Evaluating posaconazole, its pharmacology, efficacy and safety for the prophylaxis and treatment of fungal infections","volume":"23","author":"Panagopoulou","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"993","DOI":"10.2165\/00003495-200868070-00008","article-title":"Posaconazole","volume":"68","author":"Frampton","year":"2008","journal-title":"Drugs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.17650\/1818-8346-2022-17-2-121-133","article-title":"Intravenous posaconazole: Key features of clinical pharmacology and practical applications","volume":"17","author":"Veselov","year":"2022","journal-title":"Oncogematologiya"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.62400\/jbs.v5i2.6187","article-title":"The posaconazole and its pharmacologic and clinical uses: An antifungal drugs: Potentials of posaconazole","volume":"5","author":"Alghamdi","year":"2022","journal-title":"J. Biol. Stud."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107482","DOI":"10.1016\/j.ijantimicag.2025.107482","article-title":"Posaconazole effectiveness in rare invasive fungal infections: A systematic literature review","volume":"66","author":"Bernauer","year":"2025","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chai, S., Zhan, J.L., Zhao, L.M., and Liu, X.D. (2022). Safety of triazole antifungals: A pharmacovigilance study from 2004 to 2021 based on FAERS. Ther. Adv. Drug Saf., 13.","DOI":"10.1177\/20420986221143266"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/jac\/dkae479","article-title":"Efficacy and safety of posaconazole and liposomal amphotericin B use for prophylaxis of invasive fungal infections in a paediatric and young adult haemato-oncological population","volume":"80","author":"Chiusaroli","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s12288-018-0916-2","article-title":"Efficacy of posaconazole prophylaxis in patients with acute myeloid leukemia undergoing induction chemotherapy: An observational study in resource limited settings","volume":"34","author":"Bansal","year":"2018","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105886","DOI":"10.1016\/j.ijantimicag.2020.105886","article-title":"Itraconazole vs. posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia undergoing intensive chemotherapy: A retrospective study","volume":"55","author":"Copley","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1086\/504328","article-title":"Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections","volume":"42","author":"Raad","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e14045","DOI":"10.1111\/tid.14045","article-title":"Incidence of breakthrough fungal infections on isavuconazole prophylaxis compared to posaconazole and voriconazole","volume":"25","author":"Scott","year":"2023","journal-title":"Transpl. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3390\/pharmacy2010098","article-title":"Posaconazole: A review of drug interactions with HIV antiretroviral agents","volume":"2","author":"Poulakos","year":"2014","journal-title":"Pharmacy"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shi, C., Ye, J., Xie, Y., Dong, R., Jin, W., Wang, L., Fang, Y., Shan, Q., and Lin, N. (2022). Cost-effectiveness of posaconazole vs. first-generation triazoles for the prevention of invasive fungal infections among high-risk patients with hematological malignancies in China. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.884846"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1007\/s00228-024-03756-9","article-title":"Approaches for posaconazole therapeutic drug monitoring and their clinical benefits","volume":"80","author":"Wang","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, T., Shen, Y., and Feng, S. (2022). Clinical research advances of isavuconazole in the treatment of invasive fungal diseases. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1049959"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wu, L., Li, S., Gao, W., Zhu, X., Luo, P., Xu, D., Liu, D., and He, Y. (2023). Real-world, multicenter case series of patients treated with isavuconazole for invasive fungal disease in China. Microorganisms, 11.","DOI":"10.3390\/microorganisms11092229"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1186\/s12967-024-05895-0","article-title":"Inhalation of itraconazole mitigates bleomycin-induced lung fibrosis via regulating SPP1 and C3 signaling pathway pivotal in the interaction between phagocytic macrophages and diseased fibroblasts","volume":"22","author":"Pan","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/myc.13622","article-title":"A systematic review and meta-analysis of efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections","volume":"66","author":"Kato","year":"2023","journal-title":"Mycoses"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"ofae223","DOI":"10.1093\/ofid\/ofae223","article-title":"Isavuconazole for the treatment of fungal infections: A real-life experience from the fungal infection network of Switzerland (FUNGINOS)","volume":"11","author":"Couchepin","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"myae083","DOI":"10.1093\/mmy\/myae083","article-title":"A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole","volume":"62","author":"Thompson","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e00177-22","DOI":"10.1128\/aac.00177-22","article-title":"New perspectives on antimicrobial agents: Isavuconazole","volume":"66","author":"Lewis","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/16078454.2022.2076046","article-title":"Effectiveness and safety of isavuconazole prophylaxis for invasive fungal infections in the haematologic setting","volume":"27","author":"Ping","year":"2022","journal-title":"Hematology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s11046-021-00583-9","article-title":"Clinical considerations of isavuconazole administration in high-risk hematological patients: A single-center 5-year experience","volume":"186","author":"Kronig","year":"2021","journal-title":"Myopathologia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.riam.2025.02.002","article-title":"Impact of current clinical guidelines on the management of invasive fungal disease","volume":"42","year":"2025","journal-title":"Rev. Iberoam. De Micol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Batista, M.V., Ussetti, M.P., Jiang, Y., Neofytos, D., Cortez, A.C., Feriani, D., Schmidt-Filho, J., Fran\u00e7a-Silva, I.L.A., Raad, I., and Hachem, R. (2023). Comparing the real-world use of isavuconazole to other anti-Fungal therapy for invasive fungal infections in patients with and without Underlying disparities: A multi-center retrospective study. J. Fungi, 9.","DOI":"10.3390\/jof9020166"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S203","DOI":"10.1016\/j.healun.2020.01.815","article-title":"Efficacy and tolerability of isavuconazole versus posaconazole for fungal prophylaxis after lung transplantation","volume":"39","author":"Lewis","year":"2020","journal-title":"J. Heart Lung Transplant."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Al Siyabi, B., Al-Maqbali, J.S., Unnikrishnan Meenakshi, D., Wali, Y., and Al Yazidi, L. (2024). Antifungal prophylaxis utilization and the associated clinical outcomes among pediatric patients with hematological malignancies or undergoing hematopoietic stem cell transplantation. J. Clin. Med., 13.","DOI":"10.3390\/jcm13237179"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1080\/10428194.2022.2068006","article-title":"Efficacy and safety of voriconazole as invasive fungal infection prophylaxis in patients with acute myeloid leukemia","volume":"63","author":"Vockenhuber","year":"2022","journal-title":"Leuk. Lymphoma"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3324\/haematol.2011.051995","article-title":"Comparative clinical effectiveness of prophylactic voriconazole\/posaconazole to fluconazole\/itraconazole in patients with acute myeloid leukemia\/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period","volume":"97","author":"Grigg","year":"2012","journal-title":"Haematologica"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.1641","article-title":"Prospective CYP2C19-guided voriconazole prophylaxis in patients with neutropenic acute myeloid leukemia reduces the incidence of subtherapeutic antifungal plasma concentrations","volume":"107","author":"Hicks","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41397-023-00320-z","article-title":"Pharmacogenetic and clinical predictors of voriconazole concentration in hematopoietic stem cell transplant recipients receiving CYP2C19-guided dosing","volume":"23","author":"Robinson","year":"2023","journal-title":"Pharmacogenom. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10096-014-2287-4","article-title":"Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: A meta-analysis of RCTs","volume":"34","author":"Wang","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1751-553X.2007.00918.x","article-title":"Primary prophylaxis with voriconazole in patients receiving induction chemotherapy on the MRC adult acute lymphoblastic leukaemia trial (UK-ALL XII) to avoid itraconazole-enhanced vinca neurotoxicity","volume":"30","author":"Whittle","year":"2008","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1179\/joc.2011.23.1.17","article-title":"Voriconazole is effective as secondary antifungal prophylaxis in leukemia patients with prior pulmonary fungal disease: Case Series and review of literature","volume":"23","author":"Masamoto","year":"2011","journal-title":"J. Chemother."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Li, X., Hu, Q., and Xu, T. (2024). Associated factors with voriconazole plasma concentration: A systematic review and meta-analysis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1368274"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1128\/AAC.44.7.1887-1893.2000","article-title":"Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: A randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B","volume":"44","author":"Harousseau","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/jac\/dkae437","article-title":"Side effects associated with itraconazole therapy","volume":"80","author":"Osborn","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s10096-005-0080-0","article-title":"Erratum: Adverse effects of antifungal therapies in invasive fungal infections: Review and meta-analysis","volume":"25","author":"Girois","year":"2006","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1002\/jcph.772","article-title":"Adverse drug reactions in patients receiving systemic antifungal therapy at a high-complexity hospital","volume":"56","author":"Reis","year":"2016","journal-title":"J. Clin. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10096-013-1998-2","article-title":"Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation","volume":"33","author":"Blume","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.2147\/IDR.S504516","article-title":"Analysis of antifungal drug resistance among Candida spp. and other pathogenic yeasts isolated from patients in eastern Poland: Diagnostic problems","volume":"18","author":"Olender","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1080\/17460913.2024.2362128","article-title":"SUBA-itraconazole in the treatment of systemic fungal infections","volume":"19","author":"Liu","year":"2024","journal-title":"Future Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"ofae010","DOI":"10.1093\/ofid\/ofae010","article-title":"MSG-15: Super-bioavailability itraconazole Versus conventional itraconazole in the treatment of endemic mycoses\u2014A multicenter, open-label, randomized comparative trial","volume":"11","author":"Spec","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_84","first-page":"308","article-title":"Comparative clinical superiority of SUBA itraconazole with safety evaluation in the light of pharmacokinetic and pharmacodynamics investigation in healthy Indian human volunteers","volume":"37","author":"Das","year":"2025","journal-title":"Toxicol. Anal. Et Clin."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"113616","DOI":"10.1016\/j.biopha.2022.113616","article-title":"Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy","volume":"154","author":"Li","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1158\/1535-7163.MCT-20-0638","article-title":"Itraconazole exerts its antitumor effect in esophageal cancer by suppressing the HER2\/AKT signaling pathway","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00432-019-03117-5","article-title":"\u201cHedgehog pathway\u201d: A potential target of itraconazole in the treatment of cancer","volume":"146","author":"Wei","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"59","DOI":"10.37201\/req\/s01.14.2023","article-title":"New trends in antifungal treatment: What is coming up?","volume":"36","author":"Guinea","year":"2023","journal-title":"Rev. Espa\u00f1ola De Quimioter."},{"key":"ref_89","unstructured":"Clinic, M. (2025, January 28). Safety and Efficacy of PC945 (Opelconazole) in Combination with Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study). 2025. Phase 3 Trial; Protocol No. PC_ASP_006; IRB 22-008319. Available online: https:\/\/www.uclahealth.org\/clinical-trials\/safety-and-efficacy-pc945-opelconazole-combination-with."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Murray, A., Cass, L., Ito, K., Pagani, N., Armstrong-James, D., Dalal, P., Reed, A., and Strong, P. (2020). PC945, a novel inhaled antifungal agent, for the treatment of respiratory fungal infections. J. Fungi, 6.","DOI":"10.3390\/jof6040373"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/jac\/dkz280","article-title":"In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris","volume":"74","author":"Rudramurthy","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/AAC.00124-17","article-title":"In vivo biomarker analysis of the effects of intranasally dosed PC945, a novel antifungal triazole, on Aspergillus fumigatus infection in immunocompromised mice","volume":"61","author":"Kimura","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e00690","DOI":"10.1002\/prp2.690","article-title":"Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent","volume":"9","author":"Cass","year":"2021","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/AAC.02280-16","article-title":"In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection","volume":"61","author":"Colley","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6639","DOI":"10.1038\/s41598-025-87483-w","article-title":"Design, synthesis and pharmacological evaluation of 1,4-naphthoquinone- 1,2,3-triazole hybrids as new anticancer agents with multi-kinase inhibitory activity","volume":"15","author":"Mardaneh","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejmech.2019.03.023","article-title":"Tetrazole hybrids and their antifungal activities","volume":"170","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"933","DOI":"10.2174\/1389557519666181231121217","article-title":"Design, synthesis and anticancer activity of new thiazole-tetrazole or triazole hybrid glycosides targeting CDK-2 via structure-based virtual screening","volume":"19","author":"Kassem","year":"2019","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/14756366.2020.1871335","article-title":"Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR","volume":"36","author":"Khattab","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/AAC.02114-18","article-title":"Azole resistance reduces susceptibility to the tetrazole antifungal VT-1161","volume":"63","author":"Monk","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7884316","DOI":"10.1155\/2022\/7884316","article-title":"A Recent overview of 1,2,3-triazole-containing hybrids as novel antifungal agents: Focusing on synthesis, nechanism of action, and structure-activity relationship (SAR)","volume":"2022","author":"Marzi","year":"2022","journal-title":"J. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s12272-017-0887-0","article-title":"Design, synthesis and pharmacological analysis of 5-[4\u2019-(substituted-methyl)[1,1\u2019-biphenyl]-2-yl]-1H-tetrazoles","volume":"40","author":"Kamble","year":"2017","journal-title":"Arch. Pharmacal Res."},{"key":"ref_102","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 Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e01073-23","DOI":"10.1128\/mbio.01073-23","article-title":"Powering up antifungal treatment: Using small molecules to unlock the potential of existing therapies","volume":"14","author":"Shapiro","year":"2023","journal-title":"mBio"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Handelman, M., and Osherov, N. (2022). Experimental and in-host evolution of triazole resistance in human pathogenic fungi. Front. Fungal Biol., 3.","DOI":"10.3389\/ffunb.2022.957577"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:04:04Z","timestamp":1768388644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":105,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020817"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020817","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}