Due to their eukaryotic heritage, the differences between a fungal pathogen’s molecular makeup and its human host are small. Therefore, the discovery and subsequent development of novel antifungal drugs are extremely challenging. Nevertheless, since the 1940s, researchers have successfully uncovered potent candidates from natural or synthetic sources. Analogs and novel formulations of these drugs enhanced the pharmacological parameters and improved overall drug efficiency. These compounds ultimately became the founding members of novel drug classes and were successfully applied in clinical settings, offering valuable and efficient treatment of mycosis for decades. Currently, only five different antifungal drug classes exist, all characterized by a unique mode of action; these are polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. The latter, being the latest addition to the antifungal armamentarium, was introduced over two decades ago. As a result of this limited arsenal, antifungal resistance development has exponentially increased and, with it, a growing healthcare crisis. In this review, we discuss the original sources of antifungal compounds, either natural or synthetic. Additionally, we summarize the existing drug classes, potential novel candidates in the clinical pipeline, and emerging non-traditional treatment options.

Recurrent vulvovaginal candidiasis (RVVC) affects women worldwide and has far-reaching implications for a patient's quality of life. For decades, maintenance treatment using the azole antifungal fluconazole was the preferred treatment. Although efficient in controlling the symptoms, the development of azole resistance and high rates of recurrence after therapy cessation have emerged as significant limitations. Nevertheless, persistent efforts have delivered novel treatment options. Oteseconazole (VT-1161), marketed as VIVJOA, is an oral, tetrazole antifungal with unprecedented specificity toward the fungal lanosterol 14α-demethylase. We reviewed literature data on oteseconazole with a focus on the management of RVVC. Therapeutic options for RVVC are limited, and novel, innovative approaches are needed to treat this debilitating condition. These therapies need to be well-tolerated and prevent RVVC recurrence. The available clinical data show excellent safety and efficacy, with an unprecedentedly low recurrence rate. However, we believe health-care providers should be mindful to monitor for the development of resistance, as this may result in treatment failure. Further, the availability and cost may, like for most novel drugs, affect the widespread clinical implementation of VIVJOA. Altogether, we are convinced that VIVJOA is a significant advance in RVVC management.

The efficient production of biobased organic acids is crucial to move to a more sustainable and eco-friendly economy, where muconic acid is gaining interest as a versatile platform chemical to produce industrial building blocks, including adipic acid and terephthalic acid. In this study, a Saccharomyces cerevisiae platform strain able to convert glucose and xylose into cis,cis-muconic acid was further engineered to eliminate C2 dependency, improve muconic acid tolerance, enhance production and growth performance, and substantially reduce the side production of the intermediate protocatechuic acid. This was achieved by reintroducing the PDC5 gene and overexpression of QDR3 genes. The improved strain was integrated in low-pH fed-batch fermentations at bioreactor scale with integrated in situ product recovery. By adding a biocompatible organic phase consisting of CYTOP 503 and canola oil to the process, a continuous extraction of muconic acid was achieved, resulting in significant alleviation of product inhibition. Through this, the muconic acid titer and peak productivity were improved by 300% and 185%, respectively, reaching 9.3 g/L and 0.100 g/L/h in the in situ product recovery process as compared to 3.1 g/L and 0.054 g/L/h in the control process without ISPR.

Malassezia yeasts have recently gained medical importance as emerging pathogens associated with a wide range of dermatological and systemic infections. Since standardized methods for in vitro antifungal susceptibility testing have not yet been established for Malassezia spp., related diseases are always treated empirically. As a result, a high rate of recurrence and decreased antifungal susceptibility have appeared. Thus, the aims of the study were to assess and analyze the in vitro susceptibility of Malassezia isolated from pityriasis versicolor (PV) lesions and healthy controls. A total of 58 Malassezia strains isolated from PV patients and healthy controls were tested. In vitro antifungal susceptibility testing was conducted using the CLSI broth microdilution with some modifications. Candida spp. criteria established in accordance with CLSI guidelines were used for data interpretation. Ketoconazole and posaconazole seemed to be the most effective molecules against Malassezia species. However, considerable percentages of itraconazole, fluconazole, and amphotericin B ‘‘resistant’’ strains (27.6%, 29.3%, and 43.1%, respectively) were revealed in this study. Malassezia furfur, M. sympodialis, and M. globosa showed different susceptibility profiles to the drugs tested. These results emphasize the importance of accurately identifying and evaluating the antifungal susceptibility of Malassezia species in order to guide a specific and effective treatment regimen.