{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T20:26:19Z","timestamp":1771359979787,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences Middle East"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aim: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. Methods: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts\u2019 suggestions. Results: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. Discussion: The inconsistency of the results in the literature can be attributed to the studies\u2019 small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. Conclusion: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.<\/jats:p>","DOI":"10.3390\/jof8111146","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"1146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6413-3396","authenticated-orcid":false,"given":"Souha S.","family":"Kanj","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-6358","authenticated-orcid":false,"given":"Ali S.","family":"Omrani","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"},{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hail M.","family":"Al-Abdely","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Subhi","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Al-Qassimi Hospital, Emirates Health Services, Sharjah 61313, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-3865","authenticated-orcid":false,"given":"Riad El","family":"Fakih","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplant & Cellular Therapy, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibraheem","family":"Abosoudah","sequence":"additional","affiliation":[{"name":"Department of Oncology, King Faisal Specialist Hospital and Research Center, MBC J-64, Jeddah 21499, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-0076","authenticated-orcid":false,"given":"Hazar","family":"Kanj","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, American University of Beirut Medical Center, Beirut P.O. Box 11-0236, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Critical Care, \u201cEVGENIDIO\u201d Hospital, National and Kapodistrian University of Athens (NKUA), 10679 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0002-9343(82)90594-0","article-title":"Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia","volume":"72","author":"Pizzo","year":"1982","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S1473-3099(13)70112-9","article-title":"The end of the road for empirical antifungal treatment?","volume":"13","author":"Donnelly","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases\u2014Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1439-0507.2009.01691.x","article-title":"The changing face of epidemiology of invasive fungal disease in Europe","volume":"52","year":"2009","journal-title":"Mycoses"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Allaw, F., Zahreddine, N.K., Ibrahim, A., Tannous, J., Taleb, H., Bizri, A., Dbaibo, G., and Kanj, S. (2021). First Candida auris Outbreak during a COVID-19 Pandemic in a Tertiary-Care Center in Lebanon. Pathogens, 10.","DOI":"10.3390\/pathogens10020157"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMra1315399","article-title":"Invasive candidiasis","volume":"373","author":"Kullberg","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1086\/652768","article-title":"Factors Associated with Mortality in Transplant Patients with Invasive Aspergillosis","volume":"50","author":"Baddley","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jenks, J.D., Gangneux, J.P., Schwartz, I.S., Alastruey-Izquierdo, A., Lagrou, K., Thompson Iii, G.R., Lass-Fl\u00f6rl, C., and Hoenigl, M. (2020). European Confederation of Medical Mycology (ECMM) Council Investigators. Diagnosis of breakthrough fungal infections in the clinical mycology laboratory: An ECMM consensus statement. J. Fungi, 6.","DOI":"10.20944\/preprints202008.0672.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S1473-3099(15)70006-X","article-title":"British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases","volume":"15","author":"Schelenz","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/imj.12596","article-title":"Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014","volume":"44","author":"Morrissey","year":"2014","journal-title":"Intern. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bbmt.2003.09.014","article-title":"A new era of antifungal therapy","volume":"10","author":"Wingard","year":"2004","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tragiannidis, A., Kattamis, A., and Vyzantiadis, T.-A. (2021). Invasive Fungal Infections in Children with Haematological Malignancies: Diagnostic and Therapeutic Challenges. J. Fungi, 7.","DOI":"10.3390\/jof7070516"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3324\/haematol.2012.061952","article-title":"The role of antifungal treatment in hematology","volume":"97","author":"Maertens","year":"2012","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"ofac112","DOI":"10.1093\/ofid\/ofac112","article-title":"Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases","volume":"Volume 9","author":"Thompson","year":"2022","journal-title":"Open Forum Infectious Diseases"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e01487-19","DOI":"10.1128\/JCM.01487-19","article-title":"Updates in Laboratory Diagnostics for Invasive Fungal Infections","volume":"58","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/cid\/ciw592","article-title":"Galactomannan, \u03b2-D-Glucan, and Polymerase Chain Reaction\u2013Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis","volume":"63","author":"Lehrnbecher","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/myc.12443","article-title":"Biomarker-based diagnostic work-up of invasive pulmonary aspergillosis in immunocompromised paediatric patients\u2014Is Aspergillus pcr appropriate?","volume":"59","author":"Buchheidt","year":"2015","journal-title":"Mycoses"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1444-0903.2008.01649.x","article-title":"Introduction to the updated Australian and New Zealand consensus guidelines for the use of antifungal agents in the haematology\/oncology setting, 2008","volume":"38","author":"Slavin","year":"2008","journal-title":"Intern. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/cid\/ciw363","article-title":"Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act\u2013Pediatric Trials Network Steering Committee, MacGilvray S. Fluconazole prophylaxis for the prevention of candidiasis in premature infants: A meta-analysis using patient-level data","volume":"63","author":"Ericson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1056\/NEJM199903113401004","article-title":"Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia","volume":"340","author":"Walsh","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1186\/1471-2334-14-385","article-title":"Empirical antifungal therapy with an echinocandin in critically-ill patients: Prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU","volume":"14","author":"Quenot","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"i45","DOI":"10.1093\/jac\/dkq441","article-title":"Optimizing management of invasive mould diseases","volume":"66","author":"Agrawal","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.1093\/cid\/ciaa1751","article-title":"EORTC\/MSGERC definitions of invasive fungal diseases: Summary of activities of the Intensive Care Unit Working Group","volume":"72","author":"Bassetti","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1128\/AAC.49.9.3640-3645.2005","article-title":"Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: A potential risk factor for hospital mortality","volume":"49","author":"Morrell","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1093\/cid\/ciy859","article-title":"Voriconazole resistance and mortality in invasive aspergillosis: A multicenter retrospective cohort study","volume":"68","author":"Lestrade","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","first-page":"372","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"29","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1164\/rccm.201409-1701OC","article-title":"Failure of Empirical Systemic Antifungal Therapy in Mechanically Ventilated Critically Ill Patients","volume":"191","author":"Bailly","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cui, N., Wang, H., Su, L., Qiu, H., Li, R., Liu, D., and Team, C.-S. (2017). Initial therapeutic strategy of invasive candidiasis for intensive care unit patients: A retrospective analysis from the China-SCAN study. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2207-1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cmi.2014.07.006","article-title":"Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: A potential benefit from infectious disease consultation","volume":"21","author":"Farmakiotis","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jpeds.2012.01.053","article-title":"Empiric antifungal therapy and outcomes in extremely low birth weight infants with invasive candidiasis","volume":"161","author":"Greenberg","year":"2012","journal-title":"J. Pediatrics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jiac.2019.01.002","article-title":"Mortality and risk factor analysis for Candida blood stream infection: A multicenter study","volume":"25","author":"Kato","year":"2019","journal-title":"J. Infect. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/cid\/cis305","article-title":"Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control","volume":"54","author":"Kollef","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","first-page":"479413","article-title":"An Observational Study on Early Empiric versus Culture-Directed Antifungal Therapy in Critically Ill with Intra-Abdominal Sepsis","volume":"2014","author":"Lee","year":"2014","journal-title":"Crit. Care Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"117.e1","DOI":"10.1016\/j.cmi.2016.10.001","article-title":"Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units","volume":"23","author":"Montravers","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40560-020-00450-7","article-title":"Impact of host- and early treatment-related factors on mortality in ICU patients with candidemia: A bicentric retrospective observational study","volume":"8","author":"Ohki","year":"2020","journal-title":"J. Intensiv. Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/cid\/ciu074","article-title":"MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting","volume":"58","author":"Shoham","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.mycmed.2019.08.002","article-title":"Candidemia in a Portuguese tertiary care hospital: Analysis of a 2-year period","volume":"29","author":"Martins","year":"2019","journal-title":"J. De Mycol. M\u00e9dicale"},{"key":"ref_39","first-page":"6","article-title":"Impact of empirical treatment with antifungal agents on survival of patients with candidemia","volume":"32","year":"2019","journal-title":"Rev. Espa\u00f1ola Quimioter."},{"key":"ref_40","first-page":"584","article-title":"Clinical features and outcomes of Candidaemia in cancer patients: Results from Pakistan","volume":"66","author":"Raza","year":"2016","journal-title":"JPMA\u2014J. Pak. Med. Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejim.2016.08.020","article-title":"Epidemiology and outcome of candidemia in internal medicine wards: A regional study in Italy","volume":"34","author":"Tedeschi","year":"2016","journal-title":"Eur. J. Intern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1001\/jama.2016.14655","article-title":"Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: The EMPIRICUS randomized clinical trial","volume":"316","author":"Timsit","year":"2016","journal-title":"JAMA"},{"key":"ref_43","first-page":"579","article-title":"Empiric antifungal and outcome in ICU patients","volume":"97","author":"Trifi","year":"2019","journal-title":"Tunis. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13054-016-1284-7","article-title":"The paradox of the evidence about invasive fungal infections prevention","volume":"20","author":"Cortegiani","year":"2016","journal-title":"Crit. Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1200\/JOP.18.00269","article-title":"Optimal Management of Neutropenic Fever in Patients With Cancer","volume":"15","author":"Zimmer","year":"2019","journal-title":"J. Oncol. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"882","DOI":"10.6004\/jnccn.2016.0093","article-title":"Prevention and treatment of cancer-related infections, version 2.2016, NCCN clinical practice guidelines in oncology","volume":"14","author":"Baden","year":"2016","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/imj.15591","article-title":"Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021","volume":"51","author":"Douglas","year":"2021","journal-title":"Intern. Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"v111","DOI":"10.1093\/annonc\/mdw325","article-title":"Management of febrile neutropaenia: ESMO Clinical Practice Guidelines","volume":"27","author":"Klastersky","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","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_52","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_53","doi-asserted-by":"crossref","first-page":"E1672","DOI":"10.21037\/jtd.2016.12.97","article-title":"Antifungal use in intensive care units: Another uncertainty that highlights the need for precision medicine","volume":"8","author":"Moghnieh","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"i29","DOI":"10.1093\/jac\/dkx031","article-title":"Clinical considerations in the early treatment of invasive mould infections and disease","volume":"72","author":"Mercier","year":"2017","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/11\/1146\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:46Z","timestamp":1760144746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/11\/1146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,29]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jof8111146"],"URL":"https:\/\/doi.org\/10.3390\/jof8111146","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,29]]}}}