Impact of Human Serum on Pharmacodynamic Action of Echinocandins against Aspergillus spp. : an in Vitro Study

Abstract

Echinocandins represent a class of lipopeptide antifungal agents that possess a high protein binding capacity which could have an impact on their activity. This study was focusing on the role of human serum on the activities of echinocannins (caspofungin, micafungin, and anidulafungin) against Aspergillus species (A.fumigatus, A.flavus and A.terreus). The aspergillus growths have been assessed by measuring minimal effective concentrations of each (caspofungin (0.5-1 mg/L), micafungin (0.06-0.12 mg/L) and anidulafungin (0.03-0.09 mg/L). Broth microdilution method was used to study in vitro activities based on the Clinical and Laboratory Standards Institute documentation (CLSI M38-A2) by using standard medium (Roswell Park Memorial Institute (RPMI 1640)) with or without 50% human serum. Each drug was diluted ranging from 0.03-4 mg/L, inoculated with 2x104 Colony Forming Units/ml for each isolate, then incubated at 37οC for 10 hrs to A.fumigatus and A.flavus and 15 hrs to A.terreus. The fungal growth was assessed by measuring the galactomannan index for each concentration with ELISA (Platelia Aspergillus); percentage of fungal growth inhibition was measured from galactomannan index and analyzed as maximal growth inhibition (Emax) and drug concentration with 50% of growth inhibition (IC50). IC50 values of echinocandins were ranged from 0.03-0.06 mg/L without serum and 0.09-0.25 mg/L in presence of serum while Εmax values were 50(44-56)% for A.fumigatus, 70(65-74)% for A.flavus and 65(63-66)% for A.terreus without serum and 94(92-96)% for A.fumigatus, 92(91-95)% for A.flavus and 80(75-83)% for A.terreus with human serum. The study concluded the effective concentrations of all echinocandins were increased concomitantly with more than 90% fungal growth inhibition with human serum.