In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i>
<i>Aspergillus fumigatus</i> has become a significant threat in clinical settings. Cases of invasive infections with azole-resistant <i>A. fumigatus</i> isolates (ARAF) increased recently. Developing strategies for dealing with ARAF has become crucial. We here investigated th...
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MDPI AG
2022-03-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/4/350 |
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| author | Dan-Tiberiu Furnica Silke Dittmer Maike Isabell Sanders Joerg Steinmann Peter-Michael Rath Lisa Kirchhoff |
| author_facet | Dan-Tiberiu Furnica Silke Dittmer Maike Isabell Sanders Joerg Steinmann Peter-Michael Rath Lisa Kirchhoff |
| author_sort | Dan-Tiberiu Furnica |
| collection | DOAJ |
| description | <i>Aspergillus fumigatus</i> has become a significant threat in clinical settings. Cases of invasive infections with azole-resistant <i>A. fumigatus</i> isolates (ARAF) increased recently. Developing strategies for dealing with ARAF has become crucial. We here investigated the in-vitro and in-vivo activity of the imidazole luliconazole (LLCZ) against clinical ARAF. In total, the LLCZ minimum inhibitory concentrations (MICs) were tested for 101 <i>A. fumigatus</i> isolates (84 ARAF and 17 azole-susceptible <i>A. fumigatus</i> as wild-type controls) according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Additionally, antifungal activity was assessed in vitro, including an XTT planktonic growth kinetics assay and biofilm assays (crystal violet and XTT assay). Further, a single-dose LLCZ treatment (152 mg/L) was tested for seven days in vivo in a <i>Galleria mellonella</i> infection model. LLCZ showed an MIC<sub>50</sub> of 0.002 mg/L and no significant difference was found between triazole-resistant and wild-type isolates. Growth inhibition took place between 6 and 12 h after the start of incubation. LLCZ inhibited biofilm formation when added in the pre-adhesion stages. In vivo, single-dose LLCZ-treated larvae show a significantly higher survival percentage than the control group (20%). In conclusion, LLCZ has activity against planktonic cells and early biofilms of ARAF. |
| first_indexed | 2024-03-09T13:27:09Z |
| format | Article |
| id | doaj.art-4a802a52a62646deb49dd9d846a5c90d |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T13:27:09Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-4a802a52a62646deb49dd9d846a5c90d2023-11-30T21:21:52ZengMDPI AGJournal of Fungi2309-608X2022-03-018435010.3390/jof8040350In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i>Dan-Tiberiu Furnica0Silke Dittmer1Maike Isabell Sanders2Joerg Steinmann3Peter-Michael Rath4Lisa Kirchhoff5Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany<i>Aspergillus fumigatus</i> has become a significant threat in clinical settings. Cases of invasive infections with azole-resistant <i>A. fumigatus</i> isolates (ARAF) increased recently. Developing strategies for dealing with ARAF has become crucial. We here investigated the in-vitro and in-vivo activity of the imidazole luliconazole (LLCZ) against clinical ARAF. In total, the LLCZ minimum inhibitory concentrations (MICs) were tested for 101 <i>A. fumigatus</i> isolates (84 ARAF and 17 azole-susceptible <i>A. fumigatus</i> as wild-type controls) according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Additionally, antifungal activity was assessed in vitro, including an XTT planktonic growth kinetics assay and biofilm assays (crystal violet and XTT assay). Further, a single-dose LLCZ treatment (152 mg/L) was tested for seven days in vivo in a <i>Galleria mellonella</i> infection model. LLCZ showed an MIC<sub>50</sub> of 0.002 mg/L and no significant difference was found between triazole-resistant and wild-type isolates. Growth inhibition took place between 6 and 12 h after the start of incubation. LLCZ inhibited biofilm formation when added in the pre-adhesion stages. In vivo, single-dose LLCZ-treated larvae show a significantly higher survival percentage than the control group (20%). In conclusion, LLCZ has activity against planktonic cells and early biofilms of ARAF.https://www.mdpi.com/2309-608X/8/4/350ARAFluliconazolebiofilm<i>Galleria mellonella</i> |
| spellingShingle | Dan-Tiberiu Furnica Silke Dittmer Maike Isabell Sanders Joerg Steinmann Peter-Michael Rath Lisa Kirchhoff In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> Journal of Fungi ARAF luliconazole biofilm <i>Galleria mellonella</i> |
| title | In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> |
| title_full | In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> |
| title_fullStr | In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> |
| title_full_unstemmed | In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> |
| title_short | In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant <i>Aspergillus fumigatus</i> |
| title_sort | in vitro and in vivo activity of luliconazole nnd 502 against planktonic cells and biofilms of azole resistant i aspergillus fumigatus i |
| topic | ARAF luliconazole biofilm <i>Galleria mellonella</i> |
| url | https://www.mdpi.com/2309-608X/8/4/350 |
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