{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:05:21Z","timestamp":1778097921680,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"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>Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20\u201330 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a different setting with more vulnerable hosts. Patients admitted to an ICU tend to have older age and higher severity of disease. Moreover, the number of patients being treated in ICU are often immunosuppressed as a result of the widespread use of immunomodulatory agents, such as corticosteroids, chemotherapy, and biological agents. The development of Invasive Pulmonary aspergillosis (IPA) reflects a different clinical trajectory to affected patients. The increasing use of corticosteroids would probably explain the higher incidence of IPA especially in critically ill patients. In refractory septic shock, severe community-acquired pneumonia (SCAP), and acute respiratory distress syndrome (ARDS), the use of corticosteroids has re-emerged in order to decrease unacceptably high mortality rates associated with these clinical conditions. It is also pertinent to note that different reports have used different diagnosis criteria, and this might explain the different incidence rates. Another layer of complexity to better understand current IPA data is related to more aggressive acquisition of samples through invasive respiratory examinations.<\/jats:p>","DOI":"10.3390\/diagnostics13030440","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:57:07Z","timestamp":1674698227000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-5486","authenticated-orcid":false,"given":"Rafael","family":"Zaragoza","sequence":"first","affiliation":[{"name":"Critical Care Department, Hospital Universitario Dr. Peset, 46017 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-4470","authenticated-orcid":false,"given":"Jordi","family":"Sole-Violan","sequence":"additional","affiliation":[{"name":"Critical Care Department, Hospital Universitario Dr. Negr\u00edn, 35010 Las Palmas de Gran Canaria, Spain"},{"name":"Universidad Fernando Pessoa Canarias, 35010 Las Palmas de Gran Canaria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Cusack","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James\u2019s Hospital, D08 NHY1 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Critical Care Department, Hospital Universitario Joan XXIII\/URV\/IISPV, 43005 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-6539","authenticated-orcid":false,"given":"Luis Felipe","family":"Reyes","sequence":"additional","affiliation":[{"name":"Unisabana Center for Translational Science, Universidad de La Sabana, Ch\u00eda 53753, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-4063","authenticated-orcid":false,"given":"Ignacio","family":"Martin-Loeches","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James\u2019s Hospital, D08 NHY1 Dublin, Ireland"},{"name":"Department of Clinical Medicine, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"},{"name":"Hospital Clinic, Institut D\u2019Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, CIBERES, 08007 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/jama.2020.2717","article-title":"Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017","volume":"323","author":"Vincent","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"INternational study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.idc.2009.04.008","article-title":"Fungal infections in the ICU","volume":"23","author":"Zilberberg","year":"2009","journal-title":"Infect. Dis. Clin. North. Am."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Matthaiou, D.K., Christodoulopoulou, T., and Dimopoulos, G. (2015). How to treat fungal infections in ICU patients. BMC Infect. Dis., 15, Available online: http:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-015-0934-8.","DOI":"10.1186\/s12879-015-0934-8"},{"key":"ref_5","first-page":"1","article-title":"The Global Burden of Fungal Diseases","volume":"30","author":"Vallabhaneni","year":"2017","journal-title":"Infect. Dis. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/MCC.0000000000000230","article-title":"Fungal infections in the ICU: Advances in treatment and diagnosis","volume":"21","author":"Tumbarello","year":"2015","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1164\/rccm.2008-740ST","article-title":"An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients","volume":"183","author":"Limper","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Townsend, L., and Martin-Loeches, I. (2022). Invasive Aspergillosis in the Intensive Care Unit. Diagnostics, 12.","DOI":"10.3390\/diagnostics12112712"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13054-020-2808-8","article-title":"International survey on influenza-associated pulmonary aspergillosis (IAPA) in intensive care units: Responses suggest low awareness and potential underdiagnosis outside Europe","volume":"24","author":"Thevissen","year":"2020","journal-title":"Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1016\/S1473-3099(20)30847-1","article-title":"Defining and managing COVID-19-associated pulmonary aspergillosis: The 2020 ECMM\/ISHAM consensus criteria for research and clinical guidance","volume":"21","author":"Koehler","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S219","DOI":"10.1093\/mmy\/myy076","article-title":"Pathophysiological aspects of Aspergillus colonization in disease","volume":"57","author":"Gago","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1086\/513943","article-title":"Invasive Aspergillosis","volume":"26","author":"Denning","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1183\/09031936.00054810","article-title":"Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma","volume":"37","author":"Smith","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3201\/eid2701.202896","article-title":"Aspergillosis Complicating Severe Coronavirus Disease","volume":"27","author":"Marr","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s10156-004-0315-5","article-title":"Pathophysiology of pulmonary aspergillosis","volume":"10","author":"Shibuya","year":"2004","journal-title":"J. Infect. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1164\/rccm.202005-1883ED","article-title":"Invasive Aspergillus Tracheobronchitis Emerging as a Highly Lethal Complication of Severe Influenza","volume":"202","author":"Wauters","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","first-page":"1631","article-title":"Navigating the Uncertainties of COVID-19\u2013Associated Aspergillosis: A Comparison with Influenza-Associated Aspergillosis","volume":"224","author":"Lamoth","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/1751-7915.12367","article-title":"Ecology of aspergillosis: Insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species","volume":"10","author":"Paulussen","year":"2017","journal-title":"Microb. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"ofy313","DOI":"10.1093\/ofid\/ofy313","article-title":"Sepsis in Intensive Care Unit Patients: Worldwide Data From the Intensive Care over Nations Audit","volume":"5","author":"Sakr","year":"2018","journal-title":"Open Forum. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13613-020-00764-7","article-title":"Acute respiratory failure in immunocompromised patients: Outcome and clinical features according to neutropenia status","volume":"10","author":"Mokart","year":"2020","journal-title":"Ann. Intensive Care"},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00134-021-06449-4","article-title":"Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis","volume":"47","author":"Verweij","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00134-015-4201-7","article-title":"SEPsis REcognition and MAnagement (SEPREMA survey)","volume":"42","author":"Quinn","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_24","first-page":"2079","article-title":"Management of severe sepsis: Advances, challenges, and current status","volume":"9","author":"Levy","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/thoraxjnl-2014-206291","article-title":"The clinical spectrum of pulmonary aspergillosis","volume":"70","author":"Kosmidis","year":"2015","journal-title":"Thorax"},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s10096-007-0376-3","article-title":"Aspergillus infection in lung transplant patients: Incidence and prognosis","volume":"26","author":"Iversen","year":"2007","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/phar.2716","article-title":"Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation","volume":"42","author":"Nelson","year":"2022","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1007\/s00134-020-06091-6","article-title":"Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: An expert opinion","volume":"46","author":"Verweij","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s40265-021-01611-0","article-title":"The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin","volume":"81","author":"Hoenigl","year":"2021","journal-title":"Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/irv.12398","article-title":"The frequency of influenza and bacterial coinfection: A systematic review and meta-analysis","volume":"10","author":"Klein","year":"2016","journal-title":"Influenza Other Respir Viruses"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1097\/CCM.0b013e3182451fd8","article-title":"Contribution of bacterial coinfection to severe influenza infection","volume":"40","author":"Chertow","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1378\/chest.10-1396","article-title":"Community-acquired respiratory coinfection in critically III patients with pandemic 2009 influenza A(H1N1) virus","volume":"139","author":"Diaz","year":"2011","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1097\/CCM.0b013e3182416f23","article-title":"Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States","volume":"40","author":"Rice","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_35","first-page":"143","article-title":"Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis","volume":"72","author":"Schuetz","year":"2015","journal-title":"J. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00134-021-06419-w","article-title":"Pulmonary immuno-thrombosis in COVID-19 ARDS pathogenesis","volume":"47","author":"Peyvandi","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Martin-Loeches, I., JSchultz, M., Vincent, J.-L., Alvarez-Lerma, F., Bos, L.D., Sol\u00e9-Viol\u00e1n, J., Torres, A., and Rodriguez, A. (2017). Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med., 43.","DOI":"10.1007\/s00134-016-4578-y"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: From cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e422","DOI":"10.1016\/S1473-3099(19)30567-5","article-title":"Current gaps in sepsis immunology: New opportunities for translational research","volume":"19","author":"Rubio","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1128\/IAI.00298-15","article-title":"Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease","volume":"83","author":"Robinson","year":"2015","journal-title":"Infect. Immun"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"myac094","DOI":"10.1093\/mmy\/myac094","article-title":"Can bronchial secretion cultures identify the etiologic agent of COVID-19-associated pulmonary aspergillosis in ICU patients? Comparison with a species-specific Aspergillus PCR in serum","volume":"61","author":"Siopi","year":"2022","journal-title":"Med. Mycol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2002554","DOI":"10.1183\/13993003.02554-2020","article-title":"Confronting and mitigating the risk of COVID-19 associated pulmonary aspergillosis","volume":"56","author":"Youngs","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"White, P.L., Springer, J., Wise, M.P., Einsele, H., L\u00f6ffler, C., Seif, M., Prommersberger, S., Backx, M., and L\u00f6ffler, J. (2022). A Clinical Case of COVID-19-Associated Pulmonary Aspergillosis (CAPA), Illustrating the Challenges in Diagnosis (Despite Overwhelming Mycological Evidence). J. Fungi, 8.","DOI":"10.3390\/jof8010081"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1164\/rccm.201111-1978OC","article-title":"A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill Patients","volume":"186","author":"Blot","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2213-2600(21)00442-2","article-title":"Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: The French multicentre MYCOVID study","volume":"10","author":"Gangneux","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13054-021-03874-1","article-title":"Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: A European multicenter comparative cohort study","volume":"26","author":"Lemaitre","year":"2022","journal-title":"Crit. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1164\/rccm.201910-1931OC","article-title":"Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial","volume":"202","author":"Nyga","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s15010-017-1042-z","article-title":"Pharmacokinetics of antifungal drugs: Practical implications for optimized treatment of patients","volume":"45","author":"Bellmann","year":"2017","journal-title":"Infection"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1080\/14787210.2018.1528872","article-title":"Systematic review on the first line treatment of amphotericin B in critically ill adults with candidemia or invasive candidiasis","volume":"16","author":"Keane","year":"2018","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_50","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. 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