Invasive and Severe Localized Infections Caused by Fusarium Species and Other Rare Filamentous Fungi in Greece: A Prospective Epidemiological Study

Infections caused by filamentous fungi other than Aspergillus spp. or Mucorales are uncommon but often severe, particularly in immunocompromised individuals. We conducted a prospective, nationwide, multicenter study to investigate the epidemiology, clinical spectrum, antifungal susceptibility, treatment, and outcomes of invasive and severe localized rare mold infections in Greece from 2009 to 2025. We documented 118 cases, with no significant temporal trend. The most frequent underlying conditions were hematologic malignancy (27.1%), hematopoietic cell transplantation/graft-versus-host disease (11.9%), trauma or other skin conditions (13.6%), pulmonary disease or respiratory failure (5.9%), and ocular predisposing factors for keratitis (22.9%). Bloodstream and corneal infections predominated. Fusarium spp. accounted for 66.9% of cases, followed by Scedosporium apiospermum (9.3%). Six breakthrough infections occurred during mold-active prophylaxis or empirical treatment, all caused by Fusarium spp. Amphotericin B showed the greatest in vitro activity against Fusarium spp., whereas voriconazole was most active against non-Fusarium molds. Clinical outcomes did not consistently correspond with in vitro antifungal activity. Crude mortality among non-ocular infections was 44.4% and was significantly higher in patients with hematologic malignancy or hematopoietic cell transplantation than in other patients (65% vs. 28%; p = 0.018). The number of reported rare mold infections in Greece showed no increasing trend, but they were associated with substantial morbidity and high mortality, particularly among severely immunocompromised patients.