Caspofungin—A Novel Antifungal Agent

By Stan Deresinski, MD, FACP

Caspofungin (Cancidas), the first of a new class of antifungal agents, received approval by the FDA on January 26, 2001. Caspofungin is an echinocandin, a semisynthetic derivative of pneumocandin B0, which is a fermentation product of Glarea lozoyensis. It is a large (MW 1213 daltons), water soluble lipopeptide that, like other echinocandins, competitively inhibits the synthesis of b-(1,3)-D-glucan, a critical structural component of most fungal cell walls.¹

Among fungi frequently encountered in the clinic, caspofungin has in vitro and in vivo activity against Aspergillus and Candida species and is also active in animal models of Pneumocystis carinii infection. Since its mechanism of action differs from those of the polyenes and the azoles, caspofungin retains activity against many fungal organisms resistant to these 2 classes of agents. It has activity against all Candida spp., including C krusei, is fungicidal against Candida spp. in a concentration-dependent manner, and has sterilizing abilities in a murine model of pyelonephritis. When combined in vitro with amphotericin B against either C albicans, A fumigatus, Fusarium spp., or Cryptococcus neoformans, either synergy or indifference is observed; antagonism has not been described. Antagonism was also not observed in experimental infection models of candidiasis (caspofungin plus either amphotericin B or fluconazole) or aspergillosis (caspofungin plus amphotericin B).

The in vitro activity of caspofungin against the endemic fungi, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatiditis is less than that against Candida and Aspergillus. One study reported limited activity in a murine model of histoplasmosis.²

References

1. www.fda.gov/ohrms/dockets/ac/01/briefing/3676b1_01.pdf.

2. Kohler S, et al. Antimicrob Agents Chemother. 2000; 44:1850-1854.