Prevalence and diversity of antifungal resistance in <i>Fusarium</i> isolates across clinical and agricultural settings in the United States

ABSTRACT Disseminated fusariosis and chronic superficial fusariosis require effective strategies to control fungal growth and prevent systemic spread. This study presents an updated, comprehensive analysis of antifungal susceptibility in 174 Fusarium isolates collected from clinical and agricultural sources across 26 US states. Using a standardized panel of 14 antifungal agents, we compared resistance profiles across isolates to identify key epidemiological and resistance trends. Among clinical isolates, over 60% exhibited minimum inhibitory concentrations ≥ 32 µg/mL to all four clinical azoles, 49% to amphotericin B, and 74% to 5-flucytosine. Notably, nearly half of the azole-resistant clinical isolates also showed high-level resistance (≥32 µg/mL) to all five agricultural azoles. Our data demonstrate the complex, multifactorial nature of antifungal resistance across Fusarium species complexes (SCs), environmental sources, and drug classes. The widespread use of agricultural azoles may be a contributing factor to the observed prevalence of resistant Fusarium oxysporum and Fusarium solani SCs, as suggested by correlations between voriconazole and oxiconazole resistance, though causality cannot be established from this study. Resistance in Fusarium fujikuroi SC may emerge primarily in clinical settings, with potential links to agricultural azole exposure remaining uncertain. Despite high resistance to individual antifungal classes, the relatively low incidence of multidrug and pan-drug resistance, observed in fewer than 30% of clinical strains across azoles and other antifungal agents, suggests that combination therapy may still offer clinical benefit. These findings highlight the urgent need for continued antifungal resistance surveillance and the development of integrated, evidence-based strategies for the effective management of Fusarium infections.