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Anidulafungin (Eraxis®)
Anidulafungin (previously known as LY303366 and briefly also referred to as VER-002 and V-echinocandin) is a glucan synthesis inhibitor of the echinocandin structural class. It is composed of the echinocandin B nucleus with a terphenyl head group and a C5 tail.
Anidulafungin has been developed by Eli Lilly Pharmaceuticals. It has then been licensed to Versicor for development as a parenteral agent and the name of the manufacturing company has recently been changed to Vicuron. Anidulafungin is currently in clinical trials. Its trade name has not been announced.
As with other echinocandins, anidulafungin blocks the synthesis of a major fungal cell wall component, 1-3-beta glucan, presumably via inhibition of 1,3-beta-glucan synthase [1267].
Anidulafungin is active in vitro against Candida spp. However, anidulafungin MICs for C. parapsilosis and C. guilliermondii are relatively higher than those for the other species. It has been shown to be fungicidal against some isolates of C. albicans and C. glabrata [1781] [2276].
Anidulafungin does not have significant activity against Cryptococcus neoformans. Similarly, its activity against Blastomyces dermatitidis, Sporothrix schenckii, Trichosporon beigelii, Acremonium strictum, Rhizopus arrhizus, Fusarium spp. and Phialophora spp. is limited. Anidulafungin MICs for Histoplasma capsulatum, Cladophialophora bantiana, Pseudallescheria boydii, and Bipolaris spp. are also relatively high [683] [2276].
As with caspofungin, activity of anidulafungin against Aspergillus spp. has been investigated by using a distinctive parameter, "minimum effective concentration" (MEC), as well as MIC [1269]. Anidulafungin MECs for Aspergillus are in an acceptable range and lower than the MICs [1780] [1670].
For anidulafungin MICs obtained for various types of fungi, see susceptibility patterns and the susceptibility database.
Esophageal candidiasis- 100 mg day#1, then 50 mg/day
Candidemia- 200 mg day#1, then 100 mg/day
Anidulafungin (100 mg day#1, then 50 mg/day) was compared to fluconazole (200 mg/day)in a randomized double-blind trial in 601 patients with esophageal candidiasis. Endoscopi success rates (were similar between the two treatments (97.4% vs. 98.7%, respectively). However, relapse rates were higher (53%) in patients treated with anidulafungin compared to fluconazole-treated patients (19%). This higher relapse rate may have resulted from the relatively lower anidulafungin doses used in this trial. [Kraus et al. Clin Infect Dis 2004;39:770)
Anidulafungin (200 mg day #1, then 100 mg/day) was compared to intravenous fluconazole (400 mg/day) in a double-blind, randomized trial of invasive candidiasis in 256 non-neutropenic patients. The global response rate (clinical plus microbiological) at the end of IV therapy was 75.6% (96/127) with anidulafungin and 60.2 %(71/118) with fluconazole- a statistically significant difference favoring anidulafungin.
Anidulafungin must be administered intravenously
Anidulafungin is currently approved for the treatment of esophageal and invasive candidiasis.
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References
683. Espinel-Ingroff, A. 1998. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol. 36:2950-2956.
1267. Kurtz, M. B., G. Abruzzo, A. Flattery, K. Bartizal, J. A. Marrinan, W. Li, J. Milligan, K. Nollstadt, and C. M. Douglas. 1996. Characterization of echinocandin-resistant mutants of Candida albicans: Genetic, biochemical, and virulence studies. Infect. Immun. 64:3244-3251.
1269. Kurtz, M. B., I. B. Heath, J. Marrinan, S. Dreikorn, J. Onishi, and C. Douglas. 1994. Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-b-D-glucan synthase. Antimicrob. Agents Chemother. 38:1480-1489.
1670. Oakley, K. L., C. B. Moore, and D. W. Denning. 1998. In vitro activity of the echinocandin antifungal agent LY303,366 in comparison with itraconazole and amphotericin B against Aspergillus spp. Antimicrob. Agents Chemother. 42:2726-2730.
1780. Pfaller, M. A., F. Marco, S. A. Messer, and R. N. Jones. 1998. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn. Microbiol. Infect. Dis. 30:251-255.
1781. Pfaller, M. A., S. A. Messer, and S. Coffman. 1997. In vitro susceptibilities of clinical yeast isolates to a new echinocandin derivatives, LY303366, and other antifungal agents. Antimicrob. Agents Chemother. 41:763-766.
2276. Uzun, O., S. Kocagoz, Y. Cetinkaya, S. Arikan, and S. Unal. 1997. In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates. Antimicrob. Agents Chemother. 41:1156-1157.
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