[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Inhibitory and fungicidal effects of antifungal drugs against Aspergillus species in the presence of serum
Antigoni Elefanti 1, Johan W. Mouton 2, Katerina Krompa 1, Rafal Al-Saigh 1, Paul E. Verweij 2, Loukia Zerva 1 and Joseph Meletiadis 1
Author Affiliations: 1 Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens - 2 Department of Medical Microbiology, University Medical Center Nijmegen, The Netherlands
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 concentrations (FC) against 5 isolates of Aspergillus fumigatus, A. flavus and A. terreus were determined with a CLSI M38-A2 based microdilution method using the XTT methodology after 48h 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 (1.21-13.44 fold) whereas voriconazole IC and FC were decreased (0.22-0.90 fold). The amphotericin B and voriconazole FC/IC ratios did not change significantly (0.68-0.9 fold) in the presence of serum indicating that the FC increase was due to the IC increase. At supra-MEC echinocandin concentrations, fungal growth was reduced by 10-50% in presence of human serum resulting in complete inhibition of growth for some isolates. Thus, the in vitro activity of amphotericin B and echinocandins was reduced whereas that of voriconazole was enhanced in the presence of serum. These changes could not be predicted by % protein binding indicating that other factors and/or secondary mechanisms may account for the observed in vitro activity of antifungal drugs against Aspergillus species in the presence of serum.
Correspondence: Joseph Meletiadis, Ph. D., Lecturer in Mycology, Clinical Microbiology Laboratory, Attikon University Hospital, Rimini 1, Haidari, 124 62 Athens, Tel: 210-583-1909, Fax: 210-532-6421, Email: email@example.com
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