Background: The FIC index range 0.5 to 4 that is commonly used to define additivity/indifference has resulted in no interactions in most combination studies with antifungal agents and may be too broad. We reassessed this range based on the experimental variation of checkerboard technique and its ability to correctly determine purely additive interactions. Methods: Two-fold serial dilutions of voriconazole (V) and amphotericin B (A) were combined with themselves (A+A and V+V) in order to obtain additive interactions and with each other (A+V) in order to obtain antagonistic interactions. After inoculation with an A. fumigatus isolate, growth was assessed visually (VIS), turbidometrically (TUR) and colorimetrically with XTT methodology (XTT) after 24h and 48h of incubation. The MICs were defined as the lowest drug concentration showing no visual or 95% of the simulations; whereas, only 12-15% (VIS method) and 1% (TUR and XTT method) of the simulations resulted in FICmaxÂ±95% CI lower than 1.25 for the antagonistic A+V combination. Conclusions: Deviation of triplicated FIC index from the range 0.75 to 1.25 can be used to determine drug interactions.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th