Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the <i>In Vivo</i> Susceptibility in Invertebrate and Murine Models.

Détails

ID Serval
serval:BIB_2BAD0EA1E2E6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the <i>In Vivo</i> Susceptibility in Invertebrate and Murine Models.
Périodique
Antimicrobial agents and chemotherapy
Auteur(s)
Astvad KMT, Sanglard D., Delarze E., Hare R.K., Arendrup M.C.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
12/2018
Peer-reviewed
Oui
Volume
62
Numéro
12
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
<i>Candida tropicalis</i> isolates often display reduced but persistent growth (trailing) over a broad fluconazole concentration range during EUCAST susceptibility testing. Whereas weak trailing (<25% of the positive growth control) is common and found not to impair fluconazole efficacy, we investigated if more pronounced trailing impacted treatment efficacy. Fluconazole efficacy against two weakly (≤25% growth), two moderately (26% to 50% growth), and one heavily (>70% growth) trailing resistant isolate and one resistant (100% growth) isolate were investigated <i>in vitro</i> and <i>in vivo</i> (in a <i>Galleria mellonella</i> survival model and two nonlethal murine models). <i>CDR1</i> expression levels and <i>ERG11</i> sequences were characterized. The survival in fluconazole-treated <i>G. mellonella</i> was inversely correlated with the degree of trailing (71% to 9% survival in treatment groups). In mice, resistant and heavily trailing isolates responded poorly to fluconazole treatment. <i>CDR1</i> expression was significantly higher in trailing and resistant isolates than in wild-type isolates (1.4-fold to 10-fold higher). All isolates exhibited <i>ERG11</i> wild-type alleles. Heavily trailing isolates were less responsive to fluconazole in all <i>in vivo</i> models, indicating an impact on fluconazole efficacy. <i>CDR1</i> upregulation may have contributed to the observed differences. Moderately trailing isolates responded less well to fluconazole in larvae only. This confirms clinical data suggesting fluconazole is effective against infections with such isolates in less severely ill patients and supports the current 50% growth endpoint for susceptibility testing. However, it is still unclear if the gradual loss of efficacy observed for moderately trailing isolates in the larva model may be a reason for concern in selected vulnerable patient populations.
Mots-clé
EUCAST, Galleria mellonella, azoles, fluconazole, in vivo, trailing
Pubmed
Web of science
Création de la notice
17/12/2018 10:01
Dernière modification de la notice
21/12/2018 7:26
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