Antifungal and Antibiotic Drugs: A Comprehensive Review of Mechanisms, Resistance, Novel Therapeutic Strategies, and Stewardship

Background: The escalating burden of invasive fungal infections and multidrug-resistant bacterial infections constitutes a critical global public health crisis. Fungal diseases affect over 6.55 million individuals annually and contribute to more than 1.7 million deaths worldwide. Concurrently, antimicrobial resistance (AMR) caused approximately 1.27 million deaths globally in 2019 and is projected to worsen substantially without coordinated intervention. Objective: This review comprehensively examines the classification, mechanisms of action, pharmacological profiles, resistance mechanisms, and emerging therapeutic strategies for antifungal and antibiotic drugs, with an emphasis on recent clinical and preclinical advances from 2021 to 2025. Methods: A systematic narrative review was conducted through PubMed, Google Scholar, Frontiers, and WHO databases, covering peer- reviewed literature published between 2017 and 2025. Studies reporting mechanistic, clinical, or epidemiological data on antifungal and antibiotic drugs were included. Results & Conclusions: Current antifungal therapy relies on five approved drug classes—polyenes, azoles, echinocandins, pyrimidine analogues, and triterpenoids—with three novel agents (rezafungin, ibrexafungerp, oteseconazole) receiving FDA approval since 2021 and two additional agents (fosmanogepix, olorofim) in advanced clinical trials. In the antibacterial domain, newly approved agents including cefiderocol, ceftazidime-avibactam, and meropenem-vaborbactam target ESKAPE pathogens expressing carbapenemases. Cross-resistance, biofilm formation, and horizontal gene transfer continue to undermine therapeutic efficacy. Antifungal and antimicrobial stewardship programs, integrated with rapid molecular diagnostics, represent indispensable tools to optimise therapy and curtail resistance emergence. A One Health perspective is essential for addressing the environmental dimensions of resistance.