There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and “bypass” the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

The reference methodology for evaluating antifungal susceptibility is based on determining the minimum inhibitory concentration (MIC), which is the lowest drug concentration capable of inhibiting fungal growth. However, such MIC data are insufficient to measure antifungal susceptibility if a strain is heteroresistant to the tested drug. In such cases, a minority subpopulation of fungal cells, originating from an initially susceptible lineage, can grow at antifungal drug concentrations above the MIC. In studies on fluconazole heteroresistance in Cryptococcus spp., chromosomal disomy has been shown to result in the overexpression of two genes located on chromosome 1 (Chr1) linked to antifungal resistance: ERG11 and AFR1. This review addresses the underlying mechanisms of antifungal resistance, the evolution of methods for determining antifungal susceptibility, and the clinical implications of Cryptococcus heteroresistance to fluconazole. The analysis of the findings indicated a correlation between heteroresistance and adverse clinical outcomes, although this observation still lacks definite confirmation in the literature. This highlights the need to implement more efficient therapeutic strategies and improve antifungal susceptibility and heteroresistance testing.

This review article explores the potential of fermentations in the Amazon region as catalysts for economic and social development. It highlights the rich cultural and gastronomic diversity of the Amazon, focusing on indigenous fermented products. Two main products, tucupi and caxiri, are discussed in detail, emphasizing their significance in local cuisine and culture. The review examines the challenges and opportunities for industrial applications of these products, as well as their potential for social technology initiatives, particularly in the context of family farming. The sustainable production of native fermented products in the Amazon is seen as a means to preserve biodiversity, empower local communities, and promote cultural heritage. The article concludes that both industrial and social technologies have complementary roles in promoting economic growth, cultural preservation, and the well-being of the Amazon region, making it a promising hub for innovative and sustainable fermented food products on a global scale.

Cutaneous cryptococcosis is a manifestation of systemic cryptococcal infection, characterized by polymorphic skin lesions that can make diagnosis challenging. We report an HIV-positive patient with a solitary facial nodule, initially diagnosed as keratoacanthoma. Histopathology, fungal culture, and cerebrospinal fluid analysis confirmed disseminated cryptococcosis with central nervous system involvement caused by Cryptococcus neoformans genotype VNI. He was treated with amphotericin B followed by fluconazole, resulting in complete clinical resolution. This case underscores the need to consider disseminated cryptococcosis in the differential diagnosis of tumorlike skin lesions, particularly in HIV-positive patients.

The Amazon Forest harbors one of the largest fungal diversities on the planet, occupying a wide variety of ecological niches comprising terra firme (non-flooded forest), várzea (white-water floodplains), and igapó (black-water floodplains). In this review article, we examine Amazonian fungal diversity based on three complementary approaches—culture-based surveys, in situ inventories of macrofungi, and environmental DNA/metagenomic analyses—discussing advances, limitations, and contributions to regional mycological knowledge. Subsequently, we present a critical synthesis of the potential of Amazonian basidiomycetes regarding the production of metabolites with antimicrobial activity, highlighting the main genera reported in the literature, the chemical classes involved (e.g., terpenes, steroids, quinones, and bioactive peptides), and the metabolic pathways responsible for their biosynthesis. The integration between biodiversity and bioprospecting underscores the importance of Amazonian fungi both for understanding ecological processes and for the development of new solutions to the antimicrobial resistance challenge. This work seeks to fill current gaps in the academic literature and to contribute to future strategies for the conservation and sustainable use of regional mycobiota.

This case report documents the diagnosis and successful treatment of cryptococcosis caused by Cryptococcus gattii VGII in a 20‐month‐old male domestic shorthair cat from Manaus, Brazil, which was concurrently infected with feline immunodeficiency virus (FIV) and diagnosed with demodicosis. The cat presented with mucopurulent nasal discharge, cutaneous lesions on the neck, and a subcutaneous mass between the shoulder blades. Laboratory investigations, including fine‐needle aspiration cytology, fungal culture, and PCR‐RFLP genotyping, confirmed the presence of C. gattii VGII. The cat was treated with fluconazole (10 mg/kg/day) and topical fluralaner–moxidectin, resulting in complete clinical resolution of all lesions and associated symptoms. This report underscores the significance of considering cryptococcosis as a differential diagnosis in immunocompromised cats presenting with cutaneous or respiratory symptoms. Additionally, it highlights the importance of recognizing the Amazon region as an area of environmental prevalence of C. gattii VGII, reinforcing the need for awareness regarding its impact on animal health.