In vitro and in vivo interaction of caspofungin with isavuconazole against Candida auris planktonic cells and biofilms.
Candida auris
biofilms
echinocandin
isavuconazole
mouse
synergy
Journal
Medical mycology
ISSN: 1460-2709
Titre abrégé: Med Mycol
Pays: England
ID NLM: 9815835
Informations de publication
Date de publication:
04 Oct 2021
04 Oct 2021
Historique:
received:
16
03
2021
revised:
13
05
2021
accepted:
19
05
2021
pubmed:
23
5
2021
medline:
18
1
2022
entrez:
22
5
2021
Statut:
ppublish
Résumé
The in vitro and in vivo efficacy of caspofungin was determined in combination with isavuconazole against Candida auris. Drug-drug interactions were assessed utilizing the fractional inhibitory concentration indices (FICIs), the Bliss independence model and an immunocompromised mouse model. Median planktonic minimum inhibitory concentrations (pMICs) of 23 C. auris isolates were between 0.5 and 2 mg/l and between 0.015 and 4 mg/l for caspofungin and isavuconazole, respectively. Median pMICs for caspofungin and isavuconazole in combination showed 2-128-fold and 2-256-fold decreases, respectively. Caspofungin and isavuconazole showed synergism in 14 out of 23 planktonic isolates (FICI range 0.03-0.5; Bliss cumulative synergy volume range 0-4.83). Median sessile MICs (sMIC) of 14 biofilm-forming isolates were between 32 and >32 mg/l and between 0.5 and >2 mg/l for caspofungin and isavuconazole, respectively. Median sMICs for caspofungin and isavuconazole in combination showed 0-128-fold and 0-512-fold decreases, respectively. Caspofungin and isavuconazole showed synergistic interaction in 12 out of 14 sessile isolates (FICI range 0.023-0.5; Bliss cumulative synergy volume range 0.13-234.32). In line with the in vitro findings, synergistic interactions were confirmed by in vivo experiments. The fungal kidney burden decreases were more than three log volumes in mice treated with combination of 1 mg/kg caspofungin and 20 mg/kg isavuconazole daily; this difference was statistically significant compared with control mice (P < 0.001). Despite the favorable effect of isavuconazole in combination with caspofungin, further studies are needed to confirm the therapeutic advantage of this combination when treating an infection caused by C. auris. Candida auris poses a continuous therapeutic challenge. We demonstrate an approach where the combination of caspofungin and isavuconazole showed a potent activity against planktonic cells and biofilms. This synergism helps to expand the therapeutic options against C. auris.
Autres résumés
Type: plain-language-summary
(eng)
Candida auris poses a continuous therapeutic challenge. We demonstrate an approach where the combination of caspofungin and isavuconazole showed a potent activity against planktonic cells and biofilms. This synergism helps to expand the therapeutic options against C. auris.
Identifiants
pubmed: 34021571
pii: 6280985
doi: 10.1093/mmy/myab032
pmc: PMC8653632
doi:
Substances chimiques
Antifungal Agents
0
Nitriles
0
Pyridines
0
Triazoles
0
isavuconazole
60UTO373KE
Caspofungin
F0XDI6ZL63
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015-1023Subventions
Organisme : Medical Research Council
ID : MR/N006364/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V033417/1
Pays : United Kingdom
Organisme : Federation of European Microbiological Societies
ID : FEMS-GO-2019-502
Informations de copyright
© The Author(s) 2021. Published by Oxford University Presson behalf of The International Society for Human and Animal Mycology.
Références
Mycoses. 2019 Aug;62(8):706-709
pubmed: 31132181
Med Mycol. 2017 Jul 1;55(5):563-567
pubmed: 28204557
Med Mycol. 2020 Apr 1;58(3):404-407
pubmed: 31127836
Cold Spring Harb Perspect Med. 2014 May 01;4(5):
pubmed: 24789878
Emerg Infect Dis. 2019 Sep;25(9):1780-1781
pubmed: 31310230
J Vis Exp. 2011 Jan 30;(47):
pubmed: 21307833
Lancet Infect Dis. 2018 Dec;18(12):1298-1299
pubmed: 30293876
Antimicrob Agents Chemother. 2017 Oct 24;61(11):
pubmed: 28848002
Curr Clin Microbiol Rep. 2020 Sep;7(3):51-56
pubmed: 33178552
Antimicrob Agents Chemother. 2020 Mar 24;64(4):
pubmed: 31932367
Emerg Microbes Infect. 2020 Dec;9(1):1160-1169
pubmed: 32486923
Clin Microbiol Infect. 2018 Dec;24(12):1343.e1-1343.e4
pubmed: 30025834
Int J Mol Sci. 2021 Jan 14;22(2):
pubmed: 33466640
Fungal Genet Biol. 2019 Oct;131:103243
pubmed: 31228646
Med Mycol. 2005 Mar;43(2):133-52
pubmed: 15832557
Clin Infect Dis. 2017 Jan 15;64(2):134-140
pubmed: 27988485
Emerg Infect Dis. 2020 May;26(5):876-880
pubmed: 32310077
mSphere. 2016 Aug 18;1(4):
pubmed: 27547827
Antimicrob Agents Chemother. 2018 Sep 24;62(10):
pubmed: 30104269
Med Mycol Case Rep. 2018 Aug 11;22:35-37
pubmed: 30140604
J Med Microbiol. 2019 Sep;68(9):1353-1358
pubmed: 31271350
Med Mycol. 2020 Aug 1;58(6):721-729
pubmed: 31773169
Antimicrob Agents Chemother. 2017 Dec 21;62(1):
pubmed: 29038263
mSphere. 2020 Jun 24;5(3):
pubmed: 32581078
Sci Rep. 2020 Dec 8;10(1):21448
pubmed: 33293607
Antimicrob Agents Chemother. 2019 Jun 24;63(7):
pubmed: 31036689
Int J Antimicrob Agents. 2018 Dec;52(6):754-761
pubmed: 30145250
Med Mycol. 2017 Nov 1;55(8):859-868
pubmed: 28204571
Antiviral Res. 1990 Oct-Nov;14(4-5):181-205
pubmed: 2088205
Antimicrob Agents Chemother. 2015 Oct 19;60(1):229-38
pubmed: 26482310
J Intensive Care. 2018 Oct 29;6:69
pubmed: 30397481
Clin Infect Dis. 2019 May 30;68(12):1981-1989
pubmed: 30289478
Emerg Infect Dis. 2017 Feb;23(2):328-331
pubmed: 28098553
J Antimicrob Chemother. 2018 Apr 1;73(4):891-899
pubmed: 29325167
Front Microbiol. 2020 May 20;11:957
pubmed: 32508780
Antimicrob Agents Chemother. 2021 Mar 18;65(4):
pubmed: 33431416
J Fungi (Basel). 2021 Feb 04;7(2):
pubmed: 33557026
Br J Haematol. 2004 Jul;126(2):165-75
pubmed: 15238137
Clin Microbiol Infect. 2019 May;25(5):634.e1-634.e4
pubmed: 30771532
J Fungi (Basel). 2020 Nov 29;6(4):
pubmed: 33260353
mSphere. 2019 Jul 31;4(4):
pubmed: 31366705
Antimicrob Agents Chemother. 2020 Jan 27;64(2):
pubmed: 31791945