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Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives

Summary

This review examines how doctors treat serious fungal infections and the growing problem of fungi becoming resistant to medications. The authors discuss different antifungal drugs, how they work, and why some fungi are becoming harder to treat. They emphasize that controlling fungal resistance requires coordinated efforts across hospitals, farms, and communities, especially since some agricultural pesticides are creating resistant strains that spread to sick patients.

Background

Invasive fungal infections (IFIs) cause over 1.5 million deaths annually, particularly affecting immunocompromised populations. Despite their clinical and economic burden exceeding billions in healthcare costs, fungal infections remain underprioritized in public health agendas compared to other infectious diseases. The emergence of multidrug-resistant pathogens like Candida auris and azole-resistant Aspergillus fumigatus poses significant therapeutic challenges.

Objective

This review examines the current landscape of antifungal therapy, focusing on advances in drug classes, pharmacokinetics/pharmacodynamics, emerging resistance patterns, and clinical applications. The authors analyze mechanisms of action, epidemiology of resistance, and innovative therapeutic strategies to address unmet needs in antifungal treatment.

Results

The review identifies key advances including next-generation echinocandins (rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim) with improved efficacy against resistant strains. Geographic variation in resistance rates is documented, with azole-resistant A. fumigatus exceeding 10-20% in Europe and environmental resistance (TR34/L98H mutation) linked to agricultural fungicide use; C. auris shows near-universal fluconazole resistance (>90%) globally.

Conclusion

Effective management of IFIs requires multidisciplinary collaboration, enhanced surveillance systems, rapid diagnostics, and antifungal stewardship programs. A ‘One Health’ approach integrating agricultural, clinical, and environmental perspectives is essential to mitigate resistance development and optimize therapeutic outcomes.
  • Published in:Infectious Disease Reports,
  • Study Type:Literature Review,
  • Source: PMC12386373, PMID: 40863253, DOI: 10.3390/idr17040091
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