A Review of the Therapeutic Challenges and Novel Treatment Options in Mitigating Invasive Mycosis Associated with Aspergillus, Candida, Cryptococcus, and Pneumocystis

Globally, invasive fungal diseases are increasing in incidence and are associated with high rates of mortality. A lack of effective diagnostic protocols, antifungal resistance and poor antifungal stewardship contribute to negative outcomes. Aspergillus, Candida, Cryptococcus, and Pneumocystis are the most common pathogens associated with fatal fungal diseases. These species are responsible for 90% of reported invasive fungal deaths globally. Fungal species employ a diverse and effective array of virulence factors to sabotage, evade, and manipulate host immune systems, allowing for colonisation and dissemination in vivo. Invasive fungal infections are clinically challenging, as they penetrate organs and deep tissues, contributing to the aetiology of respiratory tract, endocarditis, meningitis, and medical device infections and resulting in false negative diagnostic attempts. The 2025 WHO report outlines a lack of diagnostic and therapeutic options available, especially in low-to-middle-income countries. Geographical and economic factors impact fungal disease and mortality rates. There is an urgent need for new approaches to combat fungal diseases clinically with improved biocompatibility profiles. This timely review discusses the prevalent invasive fungal species, namely, Candida, Aspergillus, Cryptococcus, and Pneumocystis, which have high mortality rates, as identified by the WHO priority pathogen list, and discusses recent advances in the treatment of fungal diseases. This dissemination of information is an important aspect of the United Nations Sustainable Development Goals (SDGs) and One Health.