Echinocandins are frontline antifungal drugs, and the emergence of echinocandin-resistant (ECR) species, such as Nakaseomyces glabratus, complicates patient outcomes. Intriguingly, under laboratory conditions, we previously showed that echinocandin alternation with metabolic-independent antifungals, such as amphotericin B (AMB), more effectively kills and minimizes the ECR in N. glabratus. Building upon our previous observations, we examined the efficacy of echinocandin alternation to amphotericin B (EAMB) over echinocandin monotherapy using a systemic candidiasis mouse model to assess if EAMB warrants investigation with potential for clinical evaluation. Interestingly, we show that regardless of the mice's immune status (immunocompromised and immunocompetent) and the N. glabratus isolates [high and low echinocandin tolerance (ECT)] tested, EAMB more rapidly cleared the infection, and minimized ECR in all organs tested compared to caspofungin monotherapy. Pharmacokinetic data suggested that the superiority of EAMB is due to concentration-independent killing activity of liposomal AMB. Although biomarkers suggested higher kidney and liver damage in the EAMB group, histological analysis showed similar damage among both groups. Collectively, using comprehensive ex vivo and in vitro/in vivo experimental conditions, we introduce a novel antifungal therapeutic regimen, which effectively minimizes the ECT and ECR rate in N. glabratus and lays the foundation for in-human studies and clinical trials.

The burden of fungal infections on human health is increasing worldwide. Aspergillus, Candida, and Cryptococcus are the top three human pathogenic fungi that are responsible for over 90% of infection-related deaths. Moreover, effective antifungal therapeutics are lacking, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proved not only to be more efficient antifungal therapeutic agents but also to overcome resistance against fungal medication. This review will examine the limitations of standard antifungal therapy as well as focus on the development of nanomaterials.

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.