Colistin and Isavuconazole Interact Synergistically In Vitro against and .

The in vitro interactions of isavuconazole in combination with colistin were evaluated against 55 clinical species isolates belonging to the five most important species (, , , , and ) responsible for human aspergillosis by a microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method for antifungal susceptibility testing. Selected isolates (, = 10; , = 15) were additionally evaluated by an agar diffusion assay using isavuconazole gradient concentration strips with or without colistin incorporated Roswell Parc Memorial Institute (RPMI) agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index. Using the checkerboard method, combination isavuconazole-colistin was synergistic for 100% of the 15 isolates and for 60% of the 20 isolates. No interactions were found for any of the other isolates. By agar diffusion assay, minimal inhibitory concentrations (MICs) in combination decreased compared to isavuconazole alone for 92% of the isolates. No interactions were found for any isolates, but synergy was observed for 40% of the isolates. A poor essential agreement of EUCAST and gradient concentration strip MICs at ± 2 log dilutions with 0% was obtained. Antagonistic interactions were never observed regardless of the technique used.