Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against Candida albicans and Candida dubliniensis

Abstract

Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against Candida albicans and Candida dubliniensis Eszter Prépost,1 Zoltán Tóth,1 David S Perlin,2 Rudolf Gesztelyi,3 Gábor Kardos,1 Renátó Kovács1,4, Fruzsina Nagy,1 Lajos Forgács,1 László Majoros11Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 2Public Health Research Institute, New Jersey Medical School-Rutgers, Newark, NJ, USA; 3Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 4Faculty of Pharmacy, University of Debrecen, Debrecen, HungaryBackground: Echinocandins are the first-line therapy for treatment of invasive Candida infections, but the mortality rate remains high, calling for novel strategies. Giving single larger echinocandin doses infrequently is an alternative regimen. Our aim was to test this novel approach in a neutropenic murine model.Materials and methods: We compared the in vivo efficacy of single 10 and 40 mg/kg of caspofungin (2.5× and 10× the normal humanized dose) to that of the same cumulative doses of daily 2 and 8 mg/kg doses for 5 days against 2 each of wild-type C. albicans and C. dubliniensis as well as echinocandin resistant C. albicans. As a comparator, we tested daily 1 mg/kg amphotericin B.Results: In lethality experiments, all caspofungin and amphotericin B regimens improved survival against wild-type C. albicans and C. dubliniensis clinical isolates (P