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

<b>Background/Objectives.</b> Pulmonary aspergillosis is a severe respiratory infection caused by <i>Aspergillus</i> 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 <i>Aspergillus</i> spp. isolated from respiratory samples. <b>Methods</b>. 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. <b>Results</b>. Among 36 <i>Aspergillus</i> spp. isolates, only <i>A. fumigatus</i> strains showed both synergy and additivity episodes. <i>A. niger</i> reported the highest antagonism percentage, while <i>A. terreus</i> revealed several indifference episodes. <b>Conclusions</b>. Isavuconazole and amphotericin B remain fundamental therapeutical alternatives, including a possible synergic effect against <i>A. fumigatus</i>. On the basis of this species-related difference, further studies will be essential to investigate different antifungal drug combinations against filamentous fungi isolates.