The Influence of Human Sera on the In Vitro Activity of MK-0991 against Aspergillus fumigatus.



Background: There have been several reports that the activity of echinocandin antifungal agents is either not affected or is decreased in the presence of human sera. It is known that these drugs are bound greater than 80% in animal and human sera. The activity of the echinocandin MK-0991 (Merck), a 1,3 D glucan synthase inhibitor, was studied against Aspergillus with and without the presence of human sera. Methods: Conidia of A. fumigatus formed germlings after overnight culture in RPMI 1640. MK-0991 was then added with or without the presence of serum and the germlings were incubated at 37oC for 24 hours. Results: 5% human serum in RPMI 1640 alone did not significantly inhibit the growth of A. Fumigatus in vitro (n=10) MK-0991 in RPMI exhibited dose dependent inhibition, with 0.05 mcg/ml, and 0.025 mcg/ml inhibiting 25% +/- 5%, and 11.6% +/-1% (n=3, p<.01 the="" addition="" of="" human="" sera="" to="" mk-0991="" at="" mcg="" and="" increased="" inhibition="" p="" lower="" concentrations="" serum="" also="" potentiated="" drug="" activity.="" mechanism="" this="" action="" is="" as="" yet="" undefined.="" effect="" was="" further="" seen="" when="" using="" that="" had="" been="" degraded="" in="" laboratory="" with="" loss="" its="" activity="" against="" aspergillus="" alone="" demonstrated="" no="" hyphae="" where="" inactive="" showed="" restoration="" low="" sera.="" conclusion:="" contrast="" reports="" other="" echinocandins="" study="" suggests="" acts="" synergistically="" enhance="" inhibitory="" vitro="" a.="" fumigatus.="">

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39th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 39th