A novel zinc-chelating compound has antifungal activity against a wide range of Candida species, including multidrug-resistant Candida auris.

Objectives: In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals. Methods: The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe. Results: A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris. We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo. APC6 disrupted the biofilms formed by Candida species. Conclusions: This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis.

Progressive Severe Hemophagocytic Syndrome due to disseminated Histoplasmosis in a Patient with HIV-1 Infection.

Histoplasmosis is caused by Histoplasma capsulatum and is prevalent in areas of the world where H. capsulatum is endemic. We herein report a patient diagnosed with HIV-1 who developed histoplasmosis from a non-H. capsulatum endemic area who experienced severe hemophagocytic syndrome due to a delayed diagnosis. The patient's symptoms emerged four years after residing in regions with a high histoplasmosis prevalence. The unrestricted administration of antifungal medication for oral candidiasis delayed the diagnosis because it improved the patient's condition. This case underscores the importance of prudent antifungal drug use in undiagnosed disseminated conditions and evaluating the travel history going back several years to facilitate a diagnosis.