Human infections caused by filamentous basidiomycetes: A global systematic review

Abstract

Filamentous basidiomycetes are increasingly recognized as causes of diverse human disease, yet knowledge of their clinical spectrum, diagnosis, treatment, antifungal susceptibility, and outcomes remains fragmented. We systematically reviewed published clinically significant human infections caused by filamentous basidiomycetes. Clinical, microbiological, radiological, treatment, susceptibility, and outcome data were extracted, cases from India were compared with those from the rest of the world (RoW), and logistic regression identified independent mortality predictors. Antifungal susceptibility data were summarized descriptively. We included 253 cases from 112 studies, comprising 56 from India and 197 from RoW. Respiratory or sinonasal disease without demonstrated tissue invasion predominated, although invasive and localized/non-invasive disease also occurred. Among patients with known immune status, 61.7% were immunocompetent, significantly more frequently in India. Schizophyllum commune (38.3%), Bjerkandera adusta (29.2%), and Hormographiella aspergillata (9.5%) predominated. Molecular sequencing was used for species-level identification in 62.5% of cases. Outcomes were available for 238 patients; 33 died (13.9%). Immunocompromised status (adjusted odds ratio [aOR], 7.12; 95% CI, 1.44–35.19) and histologic invasion (aOR, 3.19; 95% CI, 1.10–9.28) independently predicted mortality, whereas surgery was associated with lower observed mortality (aOR, 0.07; 95% CI, 0.01–0.66), although causality cannot be inferred. Amphotericin B and mold-active triazoles, particularly voriconazole, posaconazole, and isavuconazole, showed the most favorable in vitro activity, whereas fluconazole, 5-flucytosine, and echinocandins showed limited activity. Filamentous basidiomycetes cause a broad spectrum of disease in immunocompetent and immunocompromised hosts. Molecular identification is essential for accurate diagnosis, while immune status and tissue invasion are important independent determinants of adverse clinical outcomes.