Isavuconazole and Amphotericin B Synergic Antifungal Activity: In Vitro Evaluation on Pulmonary Aspergillosis Molds Isolates

Pulmonary aspergillosis is a severe respiratory infection caused by Aspergillus spp., whose resistance profiles and invasive attitude complicate therapeutical strategies. Several aspergillosis cases emerged as superinfections during the SARS-CoV-2 pandemic when isavuconazole and amphotericin B became essential antifungal alternatives. The main purpose of the present study was to investigate a possible synergic activity between these molecules against Aspergillus spp. isolated from respiratory samples. Methods. The gradient test method detected isavuconazole and amphotericin B MIC values, prompting an arrangement of their combination into an R.P.M.I. agar medium. According to Liofilchem s.r.l. instructions, the FIC index was used to establish synergy, additivity, indifference, or antagonism. Results. Among 36 Aspergillus spp. isolates, only A. fumigatus strains showed both synergy and additivity episodes. A. nigerreported the highest antagonism percentage, while A. terreus revealed several indifference episodes. Conclusions. Isavuconazole and amphotericin B remain fundamental therapeutical alternatives, including a possible synergic effect against A. fumigatus. On the basis of this species-related difference, further studies will be essential to investigate different antifungal drug combinations against filamentous fungi isolates.