Anidulafungin Pharmacokinetics and Microbial Response in Neutropenic Mice with Disseminated Candidiasis

Publisher Website
Google Scholar
Abstract
Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of Candida glabrata . Anidulafungin produced a maximal fungal kill ( E max ) of 1.4 to 1.9 log 10 CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an E max of 1.3 log 10 CFU/g in mice infected with fluconazole-susceptible C. glabrata , but the E max was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of ≥32 mg/liter. Amphotericin B achieved an E max of 4.2 log 10 CFU/g in mice infected with amphotericin B-susceptible C. glabrata , but the E max was 0 for mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (±4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of ≥8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.

This publication has 24 references indexed in Scilit: