Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.