{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:52:01Z","timestamp":1777949521945,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute\/National Institutes of Health","award":["U01CA287008"],"award-info":[{"award-number":["U01CA287008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Invasive pulmonary mold infections (IPMIs) are critical complications in immunocompromised patients, contributing significantly to morbidity and mortality. Diagnosing pathogens like Aspergillus species (spp.) and the Mucorales remains challenging due to non-specific clinical presentations and the limitations of traditional culture methods. This review provides an up-to-date synopsis of IPMI diagnostic tools, focusing on their diagnostic performance, turnaround time (TAT), and cost-effectiveness. We conducted a narrative review of the current literature regarding clinical evaluation, radiographic findings, invasive diagnostics, and non-invasive assays, including next-generation sequencing (NGS) and volatile organic compounds (VOCs). Chest computerized tomography (CT) remains a vital first step, though classic signs like the \u201chalo\u201d or \u201creverse halo\u201d are neither sensitive nor specific. Traditional diagnostics are limited by low sensitivity and delayed results. While plasma microbial cell-free DNA (mcfDNA) NGS offers rapid TAT (24\u201348 h) and high specificity, its suboptimal sensitivity for Aspergillus spp. (&lt;50%) and high cost remain significant barriers. Investigational VOC \u201cbreath tests\u201d show promising sensitivity (77\u201396%) but lack standardization. Future research must prioritize the standardization of non-invasive microbiologic testing modalities, particularly those with rapid TAT such as bedside \u201cbreath tests\u201d and high-throughput mcfDNA NGS. Development of clinical algorithms that balance cost-effectiveness with timely pathogen diagnosis based on the patient\u2019s degree of immunosuppression is essential to improve survival in high-risk populations.<\/jats:p>","DOI":"10.3390\/diagnostics16091384","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:15:02Z","timestamp":1777853702000},"page":"1384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in the Diagnosis of Invasive Pulmonary Mold Infections: Focus on Diagnostic Performance and Cost-Effectiveness of Diagnostic Tests"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2722-7878","authenticated-orcid":false,"given":"Spyridon","family":"Papadimatos","sequence":"first","affiliation":[{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7729-0569","authenticated-orcid":false,"given":"Andreas","family":"Tziotis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panos","family":"Arvanitis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St. Louis, 1 Barnes Jewish Hospital Plaza, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-4524","authenticated-orcid":false,"given":"Audrey","family":"Le-Mahajan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-108X","authenticated-orcid":false,"given":"Dimitrios","family":"Farmakiotis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1111\/ajt.17147","article-title":"A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients","volume":"22","author":"Azar","year":"2022","journal-title":"Am. 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