{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:06:48Z","timestamp":1788376008251,"version":"build-2803163510"},"reference-count":112,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Invasive pulmonary aspergillosis (IPA), traditionally associated with severe immunosuppression and neutropenia, is increasingly reported among non-neutropenic patients. This epidemiological shift highlights the need for a revised understanding of IPA\u2019s pathogenesis, clinical presentation, and management strategies. The rising incidence in these populations likely reflects improved diagnostic capabilities and recognition of additional predisposing factors. Although profound immunosuppression remains a key risk, even moderate alterations in innate or adaptive immunity can promote Aspergillus spp. invasion. This review summarizes current knowledge and recent advances in the diagnosis and treatment of IPA. Specifically, treatment strategies must be tailored to comorbidities, infection severity, and drug tolerance. Early diagnosis and prompt antifungal therapy are crucial for improving outcomes. Voriconazole remains the first-line treatment, though therapeutic drug monitoring is essential to ensure efficacy and minimize toxicity. Isavuconazole represents an effective alternative, offering comparable efficacy, improved safety, predictable pharmacokinetics, and convenient once-daily dosing. Liposomal amphotericin B serves as a valuable option in severe or refractory cases due to its broad-spectrum activity and reduced nephrotoxicity. Supportive measures\u2014such as respiratory optimization, comorbidity management, and immunomodulatory therapies\u2014are integral to care. Prognosis depends on infection extent, immune status, and timeliness of therapy. Emerging antifungal agents, including olorofim, ibrexafungerp, and fosmanogepix, show promise against resistant Aspergillus species, expanding treatment options. Overall, IPA management in non-neutropenic patients requires a multidisciplinary, patient-centered approach integrating established antifungals, supportive care, and novel therapeutic advances.<\/jats:p>","DOI":"10.3390\/diagnostics16010034","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:30:18Z","timestamp":1766489418000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Invasive Pulmonary Aspergillosis in Non-Neutropenic Patients: An Evolving Clinical Paradigm"],"prefix":"10.3390","volume":"16","author":[{"given":"Rocco","family":"Morena","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Infectious and Tropical Diseases Unit, \u201cRenato Dulbecco\u201d Teaching Hospital of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7380-3439","authenticated-orcid":false,"given":"Helen Linda","family":"Morrone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-3732","authenticated-orcid":false,"given":"Francesca","family":"Serapide","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Infectious and Tropical Diseases Unit, \u201cRenato Dulbecco\u201d Teaching Hospital of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-4620","authenticated-orcid":false,"given":"Alessandro","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Infectious and Tropical Diseases Unit, \u201cRenato Dulbecco\u201d Teaching Hospital of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/myc.13410","article-title":"Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta-analysis","volume":"65","author":"Shi","year":"2022","journal-title":"Mycoses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/myc.13434","article-title":"COVID-19-associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID-19 patients","volume":"65","year":"2022","journal-title":"Mycoses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40121-017-0183-9","article-title":"Challenges and Solution of Invasive Aspergillosis in Non-neutropenic Patients: A Review","volume":"7","author":"Bassetti","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bocci, M.G., Cascarano, L., and Capecchi, G. (2025). Pulmonary Aspergillosis in Immunocompromised Critically Ill Patients: Prevalence, Risk Factors, Clinical Features and Diagnosis\u2014A Narrative Review. J. Fungi, 11.","DOI":"10.3390\/jof11090617"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12941-025-00794-8","article-title":"Is neutropenia still the main risk factor for invasive aspergillosis? A contemporary university hospital retrospective cohort of invasive aspergillosis in neutropenic and non-neutropenic patients","volume":"24","year":"2025","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.riam.2022.04.002","article-title":"Aspergillosis by cryptic Aspergillus species: A case series and review of the literature","volume":"39","year":"2022","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s00134-024-07341-7","article-title":"Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM","volume":"50","author":"Bassetti","year":"2024","journal-title":"Intensive Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12281-023-00459-z","article-title":"Invasive Aspergillosis and the Impact of Azole-resistance","volume":"17","author":"Bosetti","year":"2023","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_9","first-page":"56","article-title":"Invasive pulmonary aspergillosis in non-neutropenic patients","volume":"29","author":"Tejeda","year":"2016","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Azim, A., and Ahmed, A. (2024). Diagnosis and management of invasive fungal diseases in non-neutropenic ICU patients, with focus on candidiasis and aspergillosis: A comprehensive review. Front. Cell Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1256158"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zaragoza, R., Sole-Violan, J., and Cusack, R. (2023). Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients. Diagnostics, 13.","DOI":"10.3390\/diagnostics13030440"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1179\/joc.2011.23.5.290","article-title":"Invasive Pulmonary Aspergillosis in Non-Neutropenic Patients: Analysis of a 14-Month Prospective Clinical Experience","volume":"23","author":"Russo","year":"2011","journal-title":"J. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrmicro.2017.90","article-title":"Aspergillus fumigatus morphology and dynamic host interactions","volume":"15","author":"Gresnigt","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1080\/21505594.2016.1231278","article-title":"Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies","volume":"7","author":"Sheppard","year":"2016","journal-title":"Virulence"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s15010-022-01960-2","article-title":"The clinical spectrum of aspergillosis in chronic obstructive pulmonary disease","volume":"51","author":"Otu","year":"2023","journal-title":"Infection"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1183\/13993003.00583-2015","article-title":"Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management","volume":"47","author":"Denning","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Reizine, F., Pinceaux, K., Lederlin, M., Autier, B., Guegan, H., Gacouin, A., Luque-Paz, D., Boglione-Kerrien, C., Bacle, A., and Le Dar\u00e9, B. (2021). Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?. J. Fungi, 7.","DOI":"10.21203\/rs.3.rs-331976\/v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1128\/IAI.71.6.3034-3042.2003","article-title":"Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates","volume":"71","author":"Philippe","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S271","DOI":"10.1080\/13693780802227159","article-title":"Invasive aspergillosis in glucocorticoid-treated patients","volume":"47","author":"Lewis","year":"2009","journal-title":"Med. Mycol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.immuni.2024.03.005","article-title":"Myeloid C-type lectin receptors in innate immune recognition","volume":"57","author":"Yamasaki","year":"2024","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12951","DOI":"10.1111\/pim.12951","article-title":"C-type lectin receptors in antifungal immunity: Current knowledge and future developments","volume":"45","author":"Hatinguais","year":"2023","journal-title":"Parasite Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1159\/000527188","article-title":"Dectin-1\/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival","volume":"15","author":"Yoshikawa","year":"2023","journal-title":"J. Innate Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1590\/0037-8682-0314-2018","article-title":"Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: A systematic review","volume":"51","author":"Cunha","year":"2018","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s13577-023-00905-7","article-title":"Neutrophil (dys) function due to altered immuno-metabolic axis in type 2 diabetes: Implications in combating infections","volume":"36","author":"Thimmappa","year":"2023","journal-title":"Hum. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Manchon, R., Feys, S., and Hoenigl, M. (2025). Aspergillus and host-pathogen interaction: Focus on treatment-relevant aspects. Clin. Microbiol. Infect., in press.","DOI":"10.1016\/j.cmi.2025.08.030"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dewi, I.M.W., van de Veerdonk, F.L., and Gresnigt, M.S. (2017). The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus. J. Fungi, 3.","DOI":"10.3390\/jof3040055"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/cid\/ciae444","article-title":"Incidence and Risk Factors for Invasive Fungal Infections in Patients Initiating Tumor Necrosis Factor\u2013Alpha Inhibitors for Inflammatory Bowel Disease and Rheumatoid Arthritis","volume":"80","author":"Hennessee","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.3109\/13693786.2010.509744","article-title":"ICU-acquired immunosuppression and the risk for secondary fungal infections","volume":"49","author":"Monneret","year":"2011","journal-title":"Med. Mycol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ccm.2008.06.010","article-title":"The Compensatory Anti-inflammatory Response Syndrome (CARS) in Critically Ill Patients","volume":"29","author":"Ward","year":"2008","journal-title":"Clin. Chest Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1164\/rccm.202006-2605ED","article-title":"Invasive Pulmonary Aspergillosis in Ventilator-associated Pneumonia: The Hidden Enemy?","volume":"202","author":"Torres","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"de Boer, M.G.J., Jolink, H., and Halkes, C.J.M. (2011). Influence of Polymorphisms in Innate Immunity Genes on Susceptibility to Invasive Aspergillosis after Stem Cell Transplantation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018403"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Drummond, R.A., Franco, L.M., and Lionakis, M.S. (2018). Human CARD9: A Critical Molecule of Fungal Immune Surveillance. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01836"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s10875-018-0539-2","article-title":"Inherited CARD9 Deficiency: Invasive Disease Caused by Ascomycete Fungi in Previously Healthy Children and Adults","volume":"38","author":"Corvilain","year":"2018","journal-title":"J. Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jinf.2016.04.040","article-title":"Baseline cytokine profiling identifies novel risk factors for invasive fungal disease among haematology patients undergoing intensive chemotherapy or haematopoietic stem cell transplantation","volume":"73","author":"Ceesay","year":"2016","journal-title":"J. Infect."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Naik, B., Ahmed, S.M.Q., Laha, S., and Das, S.P. (2021). Genetic Susceptibility to Fungal Infections and Links to Human Ancestry. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.709315"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Calder\u00f3n-Parra, J., Moreno-Torres, V., and Mills-Sanchez, P. (2022). Association of COVID-19-Associated Pulmonary Aspergillosis with Cytomegalovirus Replication: A Case-Control Study. J. Fungi, 8.","DOI":"10.3390\/jof8020161"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S2213-2600(24)00151-6","article-title":"Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patients","volume":"12","author":"Feys","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tiew, P.Y., Thing, K.X., and Chotirmall, S.H. (2022). Clinical Aspergillus Signatures in COPD and Bronchiectasis. J. Fungi, 8.","DOI":"10.3390\/jof8050480"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.38212\/2224-6614.3547","article-title":"Aspergillosis: A comprehensive review of pathogenesis, drug resistance, and emerging therapeutics","volume":"33","author":"Singh","year":"2025","journal-title":"J. Food Drug Anal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e0163323","DOI":"10.1128\/mbio.01633-23","article-title":"Dysregulated pulmonary inflammatory responses exacerbate the outcome of secondary aspergillosis following influenza","volume":"14","author":"Lee","year":"2023","journal-title":"MBio"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Luvanda, M.K., Posch, W., and Vosper, J. (2021). Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2. J. Fungi, 7.","DOI":"10.3390\/jof7020070"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1086\/505870","article-title":"Comparison of Epidemiological, Clinical, and Biological Features of Invasive Aspergillosis in Neutropenic and Nonneutropenic Patients: A 6-Year Survey","volume":"43","author":"Cornillet","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s12281-023-00456-2","article-title":"The Impact of Corticosteroids on the Outcome of Fungal Disease: A Systematic Review and Meta-analysis","volume":"17","author":"Li","year":"2023","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13613-021-00923-4","article-title":"Risk factors for invasive aspergillosis in ICU patients with COVID-19: Current insights and new key elements","volume":"11","author":"Montrucchio","year":"2021","journal-title":"Ann. Intensive Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/14740338.2019.1577817","article-title":"Update upon the infection risk in patients receiving TNF alpha inhibitors","volume":"18","author":"Murdaca","year":"2019","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70092","DOI":"10.1111\/myc.70092","article-title":"ESCMID-EFISG Survey on Diagnostic and Therapeutic Capacity for Invasive Fungal Infections in Belgium, the Netherlands, and Luxembourg: A Focus on High Azole Resistance","volume":"68","author":"Aerts","year":"2025","journal-title":"Mycoses"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, Z., and Zhou, L. (2025). Invasive aspergillosis in critically ill patients with diabetes mellitus: A systematic review and meta-analysis. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-025-10560-y"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, L., Gu, Y., and Wang, Y. (2021). The Clinical Characteristics of Patients With Nonneutropenic Invasive Pulmonary Aspergillosis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.631461"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.2147\/IDR.S542063","article-title":"Clinical Characteristics, Prognosis, and Risk Factors for Mortality in Influenza-Associated Pulmonary Aspergillosis and COVID-19-Associated Pulmonary Aspergillosis: A Multicenter Retrospective Study","volume":"18","author":"Jiang","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, R., Yang, L., and Fang, H. (2025). Non-invasive monitoring of Aspergillus infections in chronic lung disease patients: A combined serology and HRCT imaging approach. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1494522"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e70115","DOI":"10.1111\/myc.70115","article-title":"CT Findings for Differentiating Pulmonary Mucormycosis From Invasive Pulmonary Aspergillosis, Prior to Invasive Procedure Such as a Biopsy or Surgery: A 22-Year Single-Center Experience","volume":"68","author":"Jang","year":"2025","journal-title":"Mycoses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.cmi.2025.07.016","article-title":"Beyond guidelines: What do I need to know when dealing with fungal diagnostics?","volume":"31","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100982","DOI":"10.1016\/j.ijmmb.2025.100982","article-title":"Invasive pulmonary aspergillosis (IPA)\u2014A study of risk factors, diagnostic modalities and role of galactomannan antigen detection","volume":"58","author":"Pant","year":"2025","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e70125","DOI":"10.1111\/myc.70125","article-title":"Evaluating the Potential of Galactosaminogalactan as a Diagnostic Target for Invasive Aspergillosis","volume":"68","author":"Takazono","year":"2025","journal-title":"Mycoses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e0065125","DOI":"10.1128\/spectrum.00651-25","article-title":"Validation of serum galactomannan antigen assay for invasive pulmonary aspergillosis mortality outcome prediction","volume":"13","author":"Wu","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e0120925","DOI":"10.1128\/spectrum.01209-25","article-title":"Assessment of the 1,3-\u03b2-D-glucan test and the galactomannan antigen test in the detection of invasive fungal infections in patients with hematological diseases","volume":"13","author":"Wei","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jmii.2014.06.009","article-title":"A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-\u03b2-d-glucan for invasive fungal infection: Focus on cutoff levels","volume":"48","author":"He","year":"2015","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/cid\/cir897","article-title":"\u03b2-Glucan Antigenemia Assay for the Diagnosis of Invasive Fungal Infections in Patients With Hematological Malignancies: A Systematic Review and Meta-Analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3)","volume":"54","author":"Lamoth","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jmii.2025.06.001","article-title":"Performance of Galactomannan, Aspergillus-PCR, and Metagenomic sequencing for the diagnosis of invasive pulmonary aspergillosis in hematological patients","volume":"58","author":"Xu","year":"2025","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1038\/s41598-025-87605-4","article-title":"Clinical characteristics and prognosis of patients treated as invasive pulmonary aspergillosis outside of severe immunosuppression","volume":"15","author":"Liu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1186\/s13054-014-0458-4","article-title":"How to manage aspergillosis in non-neutropenic intensive care unit patients","volume":"18","author":"Bassetti","year":"2014","journal-title":"Crit. Care"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"M\u00e4rtson, A.-G., Alffenaar, J.-W.C., and Br\u00fcggemann, R.J. (2021). Precision Therapy for Invasive Fungal Diseases. J. Fungi, 8.","DOI":"10.3390\/jof8010018"},{"key":"ref_63","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_64","doi-asserted-by":"crossref","unstructured":"Jiang, L., and Lin, Z. (2024). Voriconazole: A review of adjustment programs guided by therapeutic drug monitoring. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1439586"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"dlaf177","DOI":"10.1093\/jacamr\/dlaf177","article-title":"Use of isavuconazole in critically ill patients in intensive care units: A prospective, observational, multicentre, cohort study","volume":"7","author":"Giacobbe","year":"2025","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ellsworth, M., and Ostrosky-Zeichner, L. (2020). Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance. J. Fungi, 6.","DOI":"10.3390\/jof6040324"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Cheng, J., Han, H., and Kang, W. (2024). Comparison of antifungal drugs in the treatment of invasive pulmonary aspergillosis: A systematic review and network meta-analysis. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1504826"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Batista, M.V., Ussetti, M.P., and Jiang, Y. (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_69","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Cerezuela, M., Maya Gallegos, C., and Marqu\u00e9s-Mi\u00f1ana, M.R. (2024). Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety. Antibiotics, 13.","DOI":"10.21203\/rs.3.rs-4027011\/v1"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.riam.2025.02.003","article-title":"Pharmacokinetic novelties of isavuconazole. Use in special situations","volume":"42","author":"Candel","year":"2025","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"728","DOI":"10.3111\/13696998.2016.1164175","article-title":"Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial","volume":"19","author":"Horn","year":"2016","journal-title":"J. Med. Econ."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.riam.2025.04.001","article-title":"Pharmacological interactions of isavuconazole","volume":"42","year":"2025","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Dagher, H., Hachem, R., and Chaftari, A.-M. (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_74","doi-asserted-by":"crossref","first-page":"ofae532","DOI":"10.1093\/ofid\/ofae532","article-title":"Evaluation of the Activity of Triazoles Against Non-fumigatus Aspergillus and Cryptic Aspergillus Species Causing Invasive Infections Tested in the SENTRY Program","volume":"11","author":"Pfaller","year":"2024","journal-title":"Open Forum Infect. 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Liposome Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s40265-016-0538-7","article-title":"Liposomal Amphotericin B (AmBisome\u00ae): A Review of the Pharmacokinetics, Pharmacodynamics, Clinical Experience and Future Directions","volume":"76","author":"Stone","year":"2016","journal-title":"Drugs"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e01876-20","DOI":"10.1128\/AAC.01876-20","article-title":"Experience with Liposomal Amphotericin B in Outpatient Parenteral Antimicrobial Therapy","volume":"65","author":"Burnett","year":"2021","journal-title":"Antimicrob. Agents Chemother"},{"key":"ref_80","first-page":"e31762","article-title":"Comparing Invasive Pulmonary Aspergillosis Mortality Between Liposomal Amphotericin B and Voriconazole in Patients With Hematological Malignancy or Hematopoietic Stem Cell Transplantation","volume":"14","author":"Mahmoud","year":"2022","journal-title":"Cureus"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1086\/525258","article-title":"Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America","volume":"46","author":"Walsh","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/0049475514543655","article-title":"Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion","volume":"44","author":"Nath","year":"2014","journal-title":"Trop. Doct"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.clinthera.2021.09.011","article-title":"Amphotericin-Associated Infusion-Related Reactions: A Narrative Review of Pre-Medications","volume":"43","author":"Scardina","year":"2021","journal-title":"Clin. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s11046-023-00727-z","article-title":"Treatment of Invasive Aspergillosis: How It\u2019s Going, Where It\u2019s Heading","volume":"188","author":"Boyer","year":"2023","journal-title":"Mycopathologia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1016\/j.ijid.2011.10.004","article-title":"The role of combination antifungal therapy in the treatment of invasive aspergillosis: A systematic review","volume":"16","author":"Garbati","year":"2012","journal-title":"Int. J. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7326\/M13-2508","article-title":"Combination Antifungal Therapy for Invasive Aspergillosis","volume":"162","author":"Marr","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1052-3359(25)00178-4","article-title":"Surgical Management Of Pulmonary Aspergillosis","volume":"3","author":"Suen","year":"1993","journal-title":"Chest Surg. Clin. N. Am."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3109\/13693786.2012.723224","article-title":"Better hospital nutrition needed to prevent and treat Aspergillus infections","volume":"51","author":"Curtis","year":"2013","journal-title":"Med. Mycol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1183\/09059180.00001011","article-title":"Pulmonary aspergillosis: A clinical review","volume":"20","author":"Kousha","year":"2011","journal-title":"Eur. Respir. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"myad074","DOI":"10.1093\/mmy\/myad074","article-title":"Invasive pulmonary aspergillosis real-world outcomes: Clinical features and risk factors associated with increased mortality","volume":"61","author":"Corbisiero","year":"2023","journal-title":"Med. Mycol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e17066","DOI":"10.7717\/peerj.17066","article-title":"Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study","volume":"12","author":"Chen","year":"2024","journal-title":"PeerJ"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Feng, Q., Ha, X., and Song, Y. (2025). Evaluation of the clinical characteristics and survival outcomes of invasive pulmonary aspergillosis patients. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1587227"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e70099","DOI":"10.1111\/myc.70099","article-title":"Epidemiology of Triazole Resistant Aspergillus fumigatus in Asia: A Systematic Review and Meta-Analysis","volume":"68","author":"Swain","year":"2025","journal-title":"Mycoses"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/1348-0421.12957","article-title":"Azole-resistant Aspergillus fumigatus as an emerging worldwide pathogen","volume":"66","author":"Toyotome","year":"2022","journal-title":"Microbiol. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S1473-3099(09)70265-8","article-title":"Azole resistance in Aspergillus fumigatus: A side-effect of environmental fungicide use?","volume":"9","author":"Verweij","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"101114","DOI":"10.1016\/j.lanmic.2025.101114","article-title":"Triazole-resistant Aspergillus fumigatus in the Netherlands between 1994 and 2022: A genomic and phenotypic study","volume":"6","author":"Song","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (EFSA), European Centre for Disease Prevention and Control (ECDC), European Chemicals Agency (ECHA), European Environment Agency (EEA), European Medicines Agency (EMA), and European Commission\u2019s Joint Research Centre (JRC) (2025). Impact of the use of azole fungicides, other than as human medicines, on the development of azole-resistant Aspergillus spp.. EFSA J., 23, e9200.","DOI":"10.2903\/j.efsa.2025.9200"},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1086\/524669","article-title":"Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes","volume":"46","author":"Pascual","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Perez, L., Corne, P., and Pasquier, G. (2023). Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses. J. Fungi, 9.","DOI":"10.3390\/jof9020211"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e01511-20","DOI":"10.1128\/AAC.01511-20","article-title":"Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis","volume":"65","author":"Kosmidis","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Bolcato, L., Thiebaut-Bertrand, A., and Stanke-Labesque, F. (2022). Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring. J. Clin. Med., 11.","DOI":"10.3390\/jcm11195756"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/cpt.620","article-title":"QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization","volume":"101","author":"Keirns","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e0017722","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_105","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, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"ref_106","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":"Mycopathologia"},{"key":"ref_107","first-page":"20499361231224980","article-title":"Update on therapeutic approaches for invasive fungal infections in adults","volume":"11","author":"Boutin","year":"2024","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Vanbiervliet, Y., Van Nieuwenhuyse, T., and Aerts, R. (2024). Review of the novel antifungal drug olorofim (F901318). BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-10143-3"},{"key":"ref_109","first-page":"100245","article-title":"Ibrexafungerp: A narrative overview","volume":"6","author":"Allaw","year":"2024","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Angulo, D.A., Alexander, B., and Rautemaa-Richardson, R. (2022). Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections. J. Fungi, 8.","DOI":"10.3390\/jof8111121"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Shaw, K.J., and Ibrahim, A.S. (2020). Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections. J. 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