In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates
<i>Aspergillus fumigatus</i> is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in <i>A. fumigatus</i> has chan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/7/12/1012 |
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| author | Sana Jemel Jacques Guillot Kalthoum Kallel Grégory Jouvion Elise Brisebard Eliane Billaud Vincent Jullien Françoise Botterel Eric Dannaoui |
| author_facet | Sana Jemel Jacques Guillot Kalthoum Kallel Grégory Jouvion Elise Brisebard Eliane Billaud Vincent Jullien Françoise Botterel Eric Dannaoui |
| author_sort | Sana Jemel |
| collection | DOAJ |
| description | <i>Aspergillus fumigatus</i> is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in <i>A. fumigatus</i> has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a <i>Galleria mellonella</i> model of invasive infection due to azole-susceptible or azole-resistant <i>A. fumigatus</i> isolates. We also sought to describe the pharmacokinetics of VRZ in the <i>G. mellonella</i> model. <i>G. mellonella</i> larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of <i>A. fumigatus</i>. Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible <i>A. fumigatus</i> isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a C<sub>min</sub> (24 h) between 0.11 and 11.30 mg/L, depending on the dose. In conclusion, <i>G. mellonella</i> is a suitable model for testing the efficacy of antifungal agents against <i>A. fumigatus</i>. |
| first_indexed | 2024-03-10T03:47:46Z |
| format | Article |
| id | doaj.art-504fd4f5edb945b68a89bd565ae82b00 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T03:47:46Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-504fd4f5edb945b68a89bd565ae82b002023-11-23T09:04:35ZengMDPI AGJournal of Fungi2309-608X2021-11-01712101210.3390/jof7121012In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> IsolatesSana Jemel0Jacques Guillot1Kalthoum Kallel2Grégory Jouvion3Elise Brisebard4Eliane Billaud5Vincent Jullien6Françoise Botterel7Eric Dannaoui8Dynamic, Ecole Nationale Vétérinaire d’Alfort, Université Paris Est Créteil, 94010 Créteil, FranceDynamic, Ecole Nationale Vétérinaire d’Alfort, Université Paris Est Créteil, 94010 Créteil, FranceFaculté de Médecine de Tunis, Université Tunis EL Manar, Tunis 1007, TunisiaDynamic, Ecole Nationale Vétérinaire d’Alfort, Université Paris Est Créteil, 94010 Créteil, FranceUnité de Neuropathologie Expérimentale, Institut Pasteur, 75015 Paris, FranceService de Pharmacologie APHP, Hôpital Européen Georges Pompidou, 75015 Paris, FranceService de Pharmacologie APHP, Hôpital Européen Georges Pompidou, 75015 Paris, FranceDynamic, Ecole Nationale Vétérinaire d’Alfort, Université Paris Est Créteil, 94010 Créteil, FranceDynamic, Ecole Nationale Vétérinaire d’Alfort, Université Paris Est Créteil, 94010 Créteil, France<i>Aspergillus fumigatus</i> is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in <i>A. fumigatus</i> has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a <i>Galleria mellonella</i> model of invasive infection due to azole-susceptible or azole-resistant <i>A. fumigatus</i> isolates. We also sought to describe the pharmacokinetics of VRZ in the <i>G. mellonella</i> model. <i>G. mellonella</i> larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of <i>A. fumigatus</i>. Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible <i>A. fumigatus</i> isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a C<sub>min</sub> (24 h) between 0.11 and 11.30 mg/L, depending on the dose. In conclusion, <i>G. mellonella</i> is a suitable model for testing the efficacy of antifungal agents against <i>A. fumigatus</i>.https://www.mdpi.com/2309-608X/7/12/1012<i>Aspergillus</i>antifungals<i>Galleria mellonella</i>voriconazoleazole resistance |
| spellingShingle | Sana Jemel Jacques Guillot Kalthoum Kallel Grégory Jouvion Elise Brisebard Eliane Billaud Vincent Jullien Françoise Botterel Eric Dannaoui In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates Journal of Fungi <i>Aspergillus</i> antifungals <i>Galleria mellonella</i> voriconazole azole resistance |
| title | In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates |
| title_full | In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates |
| title_fullStr | In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates |
| title_full_unstemmed | In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates |
| title_short | In Vivo Efficacy of Voriconazole in a <i>Galleria mellonella</i> Model of Invasive Infection Due to Azole-Susceptible or Resistant <i>Aspergillus fumigatus</i> Isolates |
| title_sort | in vivo efficacy of voriconazole in a i galleria mellonella i model of invasive infection due to azole susceptible or resistant i aspergillus fumigatus i isolates |
| topic | <i>Aspergillus</i> antifungals <i>Galleria mellonella</i> voriconazole azole resistance |
| url | https://www.mdpi.com/2309-608X/7/12/1012 |
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