title: Inhibitory and fungicidal effects of antifungal drugs against Aspergillus species in the presence of serum.
abstract: Given the high protein binding rates of antifungal drugs and the effect of serum proteins on Aspergillus growth, we investigated the in vitro pharmacodynamics of amphotericin B, voriconazole, and three echinocandins in the presence of human serum, assessing both inhibitory and fungicidal effects. In vitro inhibitory (IC) and fungicidal (FC) concentrations against 5 isolates of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus were determined with a CLSI M38-A2-based microdilution method using the XTT methodology after 48 h of incubation at 35 °C with a medium supplemented with 50% human serum. In the presence of serum, the IC and FC of amphotericin B and the IC of echinocandins were increased (1.21- to 13.44-fold), whereas voriconazole IC and FC were decreased (0.22- to 0.90-fold). The amphotericin B and voriconazole FC/IC ratios did not change significantly (0.59- to 2.33-fold) in the presence of serum, indicating that the FC increase was due to the IC increase. At echinocandin concentrations above the minimum effective concentration (MEC), fungal growth was reduced by 10 to 50% in the presence of human serum, resulting in complete inhibition of growth for some isolates. Thus, the in vitro activities of amphotericin B and echinocandins were reduced, whereas that of voriconazole was enhanced, in the presence of serum. These changes could not be predicted by the percentage of protein binding, indicating that other factors and/or secondary mechanisms may account for the observed in vitro activities of antifungal drugs against Aspergillus species in the presence of serum.
authors: Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors: Antigoni
authors: A
authors: Elefanti
authors: Johan W
authors: JW
authors: Mouton
authors: Katerina
authors: K
authors: Krompa
authors: Rafal
authors: R
authors: Al-Saigh
authors: Paul E
authors: PE
authors: Verweij
authors: Loukia
authors: L
authors: Zerva
authors: Joseph
authors: J
authors: Meletiadis
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects*; D001231:Aspergillus flavus / Q000187:drug effects; D001232:Aspergillus fumigatus / Q000187:drug effects; D054714:Echinocandins / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology; D044967:Serum / Q000737:chemistry*; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole