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Published on: December 28, 2017
Echinocandins: A ray of hope in antifungal drug therapy
1Department of Pharmacology, Bharati Vidyapeth University Medical College and Hospital, Sangli, Maharashtra, India.
Abstract:
Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of beta (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall.Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis.The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.
Insights
Echinocandin antifungals offer a safer alternative to Amphotericin B for invasive fungal infections, with lower toxicity. Their higher cost may limit use to resistant cases or salvage therapy.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections are increasing.
- Amphotericin B and azoles are traditional treatments but have significant toxicities and resistance issues.
- New antifungal agents are needed.
Purpose of the Study:
- To review the role of echinocandins as an alternative antifungal therapy.
- To compare echinocandins with existing antifungal drugs.
Main Methods:
- Review of clinical data on echinocandins (caspofungin, micafungin, anidulafungin).
- Comparison of efficacy and safety profiles against Amphotericin B and azoles.
- Pharmacoeconomic considerations.
Main Results:
- Echinocandins inhibit beta-(1,3)-D-glucan synthase, crucial for fungal cell wall integrity.
- Approved indications include candidiasis and invasive aspergillosis.
- Lower rates of infusion-related toxicity and nephrotoxicity compared to Amphotericin B.
- Comparable efficacy to Amphotericin B and fluconazole.
- Hepatotoxicity is a potential adverse effect requiring monitoring.
- Safer in patients with renal impairment.
Conclusions:
- Echinocandins represent a valuable therapeutic option for invasive fungal infections, particularly in cases of Amphotericin B toxicity or azole resistance.
- Lower toxicity profiles make them advantageous over Amphotericin B.
- Higher cost compared to azoles may restrict their use as first-line agents.
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