In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates
Azole resistance in Aspergillus fumigatus (Af) has become a widespread threat and a major concern for optimal management of patients with invasive aspergillosis (IA). Combination of echinocandins with azoles is an attractive alternative option for the treatment of IA due to azole-resistant Af strain...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1038342/full |
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| author | Sana Jemel Sana Jemel Sana Jemel Yannick Raveloarisaona Yannick Raveloarisaona Anne-Laure Bidaud Anne-Laure Bidaud Elie Djenontin Elie Djenontin Aicha Kallel Aicha Kallel Jacques Guillot Jacques Guillot Kalthoum Kallel Kalthoum Kallel Françoise Botterel Eric Dannaoui Eric Dannaoui Eric Dannaoui |
| author_facet | Sana Jemel Sana Jemel Sana Jemel Yannick Raveloarisaona Yannick Raveloarisaona Anne-Laure Bidaud Anne-Laure Bidaud Elie Djenontin Elie Djenontin Aicha Kallel Aicha Kallel Jacques Guillot Jacques Guillot Kalthoum Kallel Kalthoum Kallel Françoise Botterel Eric Dannaoui Eric Dannaoui Eric Dannaoui |
| author_sort | Sana Jemel |
| collection | DOAJ |
| description | Azole resistance in Aspergillus fumigatus (Af) has become a widespread threat and a major concern for optimal management of patients with invasive aspergillosis (IA). Combination of echinocandins with azoles is an attractive alternative option for the treatment of IA due to azole-resistant Af strains. The aim of this study was to evaluate the in vitro and in vivo combination of caspofungin (CAS) with either voriconazole (VRZ) or posaconazole (PSZ). In vitro interactions were assessed by two methods, and an animal model of IA in Galleria mellonella was used for in vivo evaluation. Assessment of efficacy was based on larvae mortality. Groups of 10 larvae were infected by 3 clinical strains of Af (azole susceptible, AfS; PSZ resistant, AfR1; VRZ and PSZ resistant strain, AfR2). In vitro, combination of CAS and azoles was indifferent against AfS, and AfR2, and a synergy was found for AfR1. When compared to VRZ monotherapy, the combination of VRZ at 4 µg/larva with CAS at 4 µg/larva improved survival of AfR2-infected larvae (p=0.0066). Combination of PSZ at 4µg/larva with CAS at 4 µg/larva improved survival of AfR1-infected larvae compared to CAS (p=0.0002) and PSZ (0.0024) monotherapy. Antagonism was never observed. In conclusion, the combination of caspofungin with azoles is a promising alternative for the treatment of azole resistant strains of Af. |
| first_indexed | 2024-04-10T22:30:12Z |
| format | Article |
| id | doaj.art-e1ddb44187434c8288d9b62c0fe641d5 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-10T22:30:12Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-e1ddb44187434c8288d9b62c0fe641d52023-01-17T06:07:11ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-01-011210.3389/fcimb.2022.10383421038342In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolatesSana Jemel0Sana Jemel1Sana Jemel2Yannick Raveloarisaona3Yannick Raveloarisaona4Anne-Laure Bidaud5Anne-Laure Bidaud6Elie Djenontin7Elie Djenontin8Aicha Kallel9Aicha Kallel10Jacques Guillot11Jacques Guillot12Kalthoum Kallel13Kalthoum Kallel14Françoise Botterel15Eric Dannaoui16Eric Dannaoui17Eric Dannaoui18Université Paris Est Créteil, Dynamyc, Créteil, FranceUniversité Tunis EL Manar, Faculté de médecine de Tunis, Tunis, TunisieUR17SP03, Centre Hospitalo-Universitaire La Rabta, Jabbari, Tunis, TunisieUnité de Parasitologie-Mycologie, Service de Microbiologie, Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Européen Georges Pompidou, Paris, FranceUniversité de Paris-Cité, Faculté Médecine, Paris, FranceUnité de Parasitologie-Mycologie, Service de Microbiologie, Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Européen Georges Pompidou, Paris, FranceUniversité de Paris-Cité, Faculté Médecine, Paris, FranceUniversité Paris Est Créteil, Dynamyc, Créteil, FranceUnité de Parasitologie-Mycologie, Service de Microbiologie, Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Européen Georges Pompidou, Paris, FranceUniversité Tunis EL Manar, Faculté de médecine de Tunis, Tunis, TunisieUR17SP03, Centre Hospitalo-Universitaire La Rabta, Jabbari, Tunis, TunisieDermatology-Parasitology-Mycology, Oniris, Nantes, FranceUniv. Angers, Univ. Brest, IRF, SFR ICAT, Angers, FranceUniversité Tunis EL Manar, Faculté de médecine de Tunis, Tunis, TunisieUR17SP03, Centre Hospitalo-Universitaire La Rabta, Jabbari, Tunis, TunisieUniversité Paris Est Créteil, Dynamyc, Créteil, FranceUniversité Paris Est Créteil, Dynamyc, Créteil, FranceUnité de Parasitologie-Mycologie, Service de Microbiologie, Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Européen Georges Pompidou, Paris, FranceUniversité de Paris-Cité, Faculté Médecine, Paris, FranceAzole resistance in Aspergillus fumigatus (Af) has become a widespread threat and a major concern for optimal management of patients with invasive aspergillosis (IA). Combination of echinocandins with azoles is an attractive alternative option for the treatment of IA due to azole-resistant Af strains. The aim of this study was to evaluate the in vitro and in vivo combination of caspofungin (CAS) with either voriconazole (VRZ) or posaconazole (PSZ). In vitro interactions were assessed by two methods, and an animal model of IA in Galleria mellonella was used for in vivo evaluation. Assessment of efficacy was based on larvae mortality. Groups of 10 larvae were infected by 3 clinical strains of Af (azole susceptible, AfS; PSZ resistant, AfR1; VRZ and PSZ resistant strain, AfR2). In vitro, combination of CAS and azoles was indifferent against AfS, and AfR2, and a synergy was found for AfR1. When compared to VRZ monotherapy, the combination of VRZ at 4 µg/larva with CAS at 4 µg/larva improved survival of AfR2-infected larvae (p=0.0066). Combination of PSZ at 4µg/larva with CAS at 4 µg/larva improved survival of AfR1-infected larvae compared to CAS (p=0.0002) and PSZ (0.0024) monotherapy. Antagonism was never observed. In conclusion, the combination of caspofungin with azoles is a promising alternative for the treatment of azole resistant strains of Af.https://www.frontiersin.org/articles/10.3389/fcimb.2022.1038342/fullAspergillus fumigatus (A. fumigatus)antifungal combinationGalleria mellonellavoriconazoleposaconazolecaspofungin |
| spellingShingle | Sana Jemel Sana Jemel Sana Jemel Yannick Raveloarisaona Yannick Raveloarisaona Anne-Laure Bidaud Anne-Laure Bidaud Elie Djenontin Elie Djenontin Aicha Kallel Aicha Kallel Jacques Guillot Jacques Guillot Kalthoum Kallel Kalthoum Kallel Françoise Botterel Eric Dannaoui Eric Dannaoui Eric Dannaoui In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates Frontiers in Cellular and Infection Microbiology Aspergillus fumigatus (A. fumigatus) antifungal combination Galleria mellonella voriconazole posaconazole caspofungin |
| title | In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates |
| title_full | In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates |
| title_fullStr | In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates |
| title_full_unstemmed | In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates |
| title_short | In vitro and in vivo evaluation of antifungal combinations against azole-resistant Aspergillus fumigatus isolates |
| title_sort | in vitro and in vivo evaluation of antifungal combinations against azole resistant aspergillus fumigatus isolates |
| topic | Aspergillus fumigatus (A. fumigatus) antifungal combination Galleria mellonella voriconazole posaconazole caspofungin |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1038342/full |
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