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[Invasive fungal infections. Epidemiology and new therapies]
1Service de Médecine interne et Maladies infectieuse, CH F. Quesnay, boulevard Sully, F 78200 Mantesla-Jolie. ftremo@hotmail.com
Abstract:
RISING INCIDENCE: In the past two decades, systemic fungal infections, essentially invasive candidiasis, but also invasive aspergillosis, has increased substantially. Despite the currently available antifungal drugs, amphotericin B (AmB), azole compounds (fluconazole or FLU, itraconazole or ITR), these infections are associated with significant morbidity and mortality. AmB remains the drug of choice for treatment of most fungal diseases because of its broad spectrum and potent fungicidal activity, but significant side effects limit its clinical utility. The azole antifungal agents are easier to take, less toxic than AmB, but their use is limited by multiazole-resistant strains. NEW ANTIFUNGAL AGENTS: Lipid formulations have recently attracted much attention due to a significantly lower toxicity: this concerns lipid formulations of AmB and perhaps nystatin in the future. New triazoles (voriconazole, ravuconazole, posaconazole) have shown a wide spectrum of action including against azole-resistant isolates. A new class of antifungal agents, lipopeptides (MK-0991, LY303366, FK463), with an original mechanism of action are being developed. These new compounds are reported to possess a large fungicidal activity against most isolates including AmB and azole-resistant strains.
Insights
Systemic fungal infections are rising, with current antifungals facing limitations. New lipid formulations and agents like triazoles and lipopeptides offer improved efficacy and safety for invasive fungal diseases.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Context:
- Systemic fungal infections, including invasive candidiasis and aspergillosis, have increased significantly over the past two decades.
- Current antifungal drugs like amphotericin B (AmB) and azoles (fluconazole, itraconazole) are associated with considerable morbidity and mortality.
- AmB, while potent, has significant side effects, and azoles face resistance issues.
Purpose:
- To review the challenges posed by rising systemic fungal infections and the limitations of existing antifungal therapies.
- To highlight the development and potential of novel antifungal agents and formulations.
- To discuss new therapeutic options for invasive fungal infections.
Summary:
- Lipid formulations of existing antifungals, such as AmB, are being developed to reduce toxicity.
- Newer triazole agents (voriconazole, ravuconazole, posaconazole) demonstrate broad-spectrum activity, including against azole-resistant fungal strains.
- Novel lipopeptide antifungals are under development, exhibiting potent fungicidal activity against resistant isolates.
Impact:
- These advancements in antifungal drug development are crucial for improving treatment outcomes in patients with invasive fungal infections.
- Newer agents and formulations promise to overcome resistance mechanisms and reduce treatment-related toxicities.
- The development of effective treatments is vital given the rising incidence and associated mortality of systemic mycoses.