In vitro interaction of isavuconazole and anidulafungin against azole-susceptible and azole-resistant Aspergillus fumigatus isolates.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
25
11
2019
revised:
24
02
2020
accepted:
15
04
2020
pubmed:
10
6
2020
medline:
25
6
2021
entrez:
10
6
2020
Statut:
ppublish
Résumé
The voriconazole and echinocandin combination has been found to be synergistic in vitro and in vivo against most Aspergillus fumigatus isolates, both with a WT azole phenotype and an azole-resistant phenotype. The interaction between isavuconazole and echinocandins is less well studied. This is especially true for azole-resistant isolates. We investigated the in vitro interaction between isavuconazole and anidulafungin for 30 A. fumigatus isolates including 18 azole-resistant isolates with various isavuconazole resistance phenotypes. The isavuconazole/anidulafungin interaction was studied by using an adapted EUCAST-based 2D (12 × 8) chequerboard broth microdilution colorimetric assay using XTT. The interaction was analysed by FIC index (FICi) analysis and Bliss independence (BI) interaction analysis. Both the FICi analysis and the BI analysis showed synergistic interaction between isavuconazole and anidulafungin for the majority of WT and azole-resistant isolates. As we did not see significant beneficial effects of combination therapy in TR46/Y121F/T289A isolates at clinically achievable drug concentrations, it is unlikely that TR46/Y121F/T289A infections would benefit from isavuconazole and anidulafungin combination therapy. In regions with high azole resistance rates this combination may benefit patients with WT disease, azole-resistant invasive aspergillosis and those with mixed azole-susceptible and azole-resistant infection, but may not be beneficial for aspergillosis due to isolates with high isavuconazole resistance, such as TR46/Y121F/T289A isolates.
Sections du résumé
BACKGROUND
The voriconazole and echinocandin combination has been found to be synergistic in vitro and in vivo against most Aspergillus fumigatus isolates, both with a WT azole phenotype and an azole-resistant phenotype. The interaction between isavuconazole and echinocandins is less well studied. This is especially true for azole-resistant isolates.
OBJECTIVES
We investigated the in vitro interaction between isavuconazole and anidulafungin for 30 A. fumigatus isolates including 18 azole-resistant isolates with various isavuconazole resistance phenotypes.
METHODS
The isavuconazole/anidulafungin interaction was studied by using an adapted EUCAST-based 2D (12 × 8) chequerboard broth microdilution colorimetric assay using XTT. The interaction was analysed by FIC index (FICi) analysis and Bliss independence (BI) interaction analysis.
RESULTS
Both the FICi analysis and the BI analysis showed synergistic interaction between isavuconazole and anidulafungin for the majority of WT and azole-resistant isolates. As we did not see significant beneficial effects of combination therapy in TR46/Y121F/T289A isolates at clinically achievable drug concentrations, it is unlikely that TR46/Y121F/T289A infections would benefit from isavuconazole and anidulafungin combination therapy.
CONCLUSIONS
In regions with high azole resistance rates this combination may benefit patients with WT disease, azole-resistant invasive aspergillosis and those with mixed azole-susceptible and azole-resistant infection, but may not be beneficial for aspergillosis due to isolates with high isavuconazole resistance, such as TR46/Y121F/T289A isolates.
Identifiants
pubmed: 32516368
pii: 5855124
doi: 10.1093/jac/dkaa185
pmc: PMC7443724
doi:
Substances chimiques
Antifungal Agents
0
Azoles
0
Fungal Proteins
0
Nitriles
0
Pyridines
0
Triazoles
0
isavuconazole
60UTO373KE
Anidulafungin
9HLM53094I
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2582-2586Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Références
Diagn Microbiol Infect Dis. 2012 Jun;73(2):135-7
pubmed: 22608136
Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38
pubmed: 29544767
Antimicrob Agents Chemother. 2002 Aug;46(8):2564-8
pubmed: 12121933
Bone Marrow Transplant. 2010 Jul;45(7):1227-33
pubmed: 20062093
Clin Microbiol Infect. 2004 Oct;10(10):925-8
pubmed: 15373889
Med Mycol. 2017 Jun 1;55(4):457-460
pubmed: 27760829
J Clin Microbiol. 2001 Sep;39(9):3402-8
pubmed: 11526191
Antimicrob Agents Chemother. 2005 Dec;49(12):4867-75
pubmed: 16304147
J Fungi (Basel). 2017 Oct 18;3(4):
pubmed: 29371573
Clin Microbiol Infect. 2008 Oct;14(10):982-4
pubmed: 18828858
Antimicrob Agents Chemother. 2005 Mar;49(3):1232-5
pubmed: 15728937
Antimicrob Agents Chemother. 2007 Mar;51(3):881-7
pubmed: 17145783
Haematologica. 2017 Mar;102(3):433-444
pubmed: 28011902
Antimicrob Agents Chemother. 2015 Mar;59(3):1738-44
pubmed: 25583716
Clin Infect Dis. 2016 Aug 15;63(4):e1-e60
pubmed: 27365388
Antimicrob Agents Chemother. 2017 Dec 21;62(1):
pubmed: 29038263
Antimicrob Agents Chemother. 2013 Feb;57(2):796-803
pubmed: 23183435
J Antimicrob Chemother. 2016 Nov;71(11):3135-3147
pubmed: 27494912
Drug Resist Updat. 2015 Jul-Aug;21-22:30-40
pubmed: 26282594
Antimicrob Agents Chemother. 2013 Nov;57(11):5438-47
pubmed: 23959322
Mycopathologia. 2014 Feb;177(1-2):11-8
pubmed: 24306184
Antimicrob Agents Chemother. 2014 Nov;58(11):6934-7
pubmed: 25136021
Antimicrob Agents Chemother. 2012 Aug;56(8):4500-3
pubmed: 22615296
J Fungi (Basel). 2018 Aug 29;4(3):
pubmed: 30158470
J Antimicrob Chemother. 2015 Jan;70(1):178-81
pubmed: 25301884
Ann Intern Med. 2015 Jan 20;162(2):81-9
pubmed: 25599346
Antimicrob Agents Chemother. 2003 Apr;47(4):1416-8
pubmed: 12654681
J Antimicrob Chemother. 2013 Feb;68(2):385-93
pubmed: 23129729
Antimicrob Agents Chemother. 2009 Jun;53(6):2382-91
pubmed: 19307368
Diagn Microbiol Infect Dis. 2018 Jan;90(1):40-43
pubmed: 29126660
J Antimicrob Chemother. 2009 Dec;64(6):1274-81
pubmed: 19841031
Diagn Microbiol Infect Dis. 2018 Jul;91(3):266-268
pubmed: 29622284
Lancet. 2016 Feb 20;387(10020):760-9
pubmed: 26684607