Aspergillus fumigatus has become a significant concern in clinical settings due to the increasing cases of invasive infections caused by azole-resistant A. fumigatus isolates (ARAF). It is essential to develop strategies to address this issue. In this study, the effectiveness of luliconazole (LLCZ), an imidazole, against clinical ARAF was investigated both in vitro and in vivo. 

The study entailed testing minimum inhibitory concentrations (MICs) of LLCZ of 101 A. fumigatus isolates; 84 ARAF and 17 azole-susceptible A. fumigatus were used as controls. Various in vitro assays were conducted to assess the antifungal activity of LLCZ, including planktonic growth kinetics and biofilm assays. Additionally, an in vivo Galleria mellonella infection model was used to test the efficacy of a single-dose LLCZ treatment. 

The results showed that LLCZ exhibited activity against planktonic cells and early biofilms of ARAF. The MIC50 of LLCZ was 0.002 mg/L, and no significant difference was observed between triazole-resistant and wild-type isolates. Growth inhibition occurred within 6 to 12 hours of incubation. LLCZ also demonstrated the ability to inhibit biofilm formation when added at the pre-adhesion stages.

 In the in vivo experiments, larvae treated with a single-dose LLCZ showed significantly higher survival rates compared to the control group. In conclusion, LLCZ demonstrated efficacy against planktonic cells and early biofilms of ARAF, suggesting its potential as an alternative treatment for systemic ARAF infections.

Source: Furnica DT, Dittmer S, Sanders MI, Steinmann J, Rath PM, Kirchhoff L. In vitro and in vivo activity of luliconazole (NND-502) against planktonic cells and biofilms of azole resistant Aspergillus fumigatus. J Fungi. 2022;8(4):350.