In vitro potency and fungicidal activity of CD101, a novel echinocandin, against recent clinical isolates of Candida spp.

Candida infections vary in severity and manifestation. Common infections include invasive bloodstream infections among hospitalized/immunocompromised patients and vulvovaginal candidiasis among women. Echinocandins and azoles are commonly utilized to treat Candida infections, although echinocandin use has been restricted to indications amenable to once-daily IV administration. CD101, a novel echinocandin with a long plasma half-life and enhanced stability, is in development for once-weekly IV administration for the treatment of candidemia and invasive candidiasis. In this study, the MIC of CD101 and comparators against 500 recent clinical Candida isolates was determined per Clinical and Laboratory Standards Institute guidelines. For select isolates, the minimum fungicidal concentration (MFC; n=49) and time-kill (n=9) of CD101 and comparators was evaluated. The MICs (μg/mL; n=100/species) for CD101, anidulafungin, fluconazole, and amphotericin B, respectively, were: C. albicans (0.008/0.03, 0.004/0.008, 0.25/4, 0.25/0.5), C. tropicalis (0.008/0.03, 0.004/0.015, 0.5/2, 0.5/1), C. parapsilosis (1/1, 0.5/2, 0.5/1, 0.5/1), C. glabrata (0.03/0.03, 0.03/0.03, 8/>32, 0.5/0.5), and C. krusei (0.03/0.03, 0.03/0.03, 32/>32, 1/1). CD101 MICs were comparable to anidulafungin and both maintained potency against fluconazole-resistant isolates. Against rare anidulafungin-resistant isolates, the MICs of CD101 and anidulafungin were elevated vs. anidulafungin-susceptible isolates. Similar to anidulafungin, CD101 was fungicidal with an MFC:MIC ratio ≤4 for 95% of evaluable isolates and resulted in 3-log killing by 24-48h for all isolates evaluated by time-kill. The potent fungicidal activity of CD101 highlights the potential clinical utility of CD101 IV for the treatment of invasive candidiasis and candidemia.