In Vitro Characterization of Twenty-One Antifungal Combinations against Echinocandin-Resistant and -Susceptible Candida glabrata

This study was designed to analyze the interaction of 21 antifungal combinations consisting of seven major antifungal agents against 11 echinocandin- susceptible and six-resistant C. glabrata isolates. The combinations were divided into five major groups and were evaluated by checkerboard, disc diffusion, and time-killing assays. Synergy based on the fractional inhibitory concentration index of ≤0.50 was observed in 17.65-29.41% of the cases for caspofungin combinations with azoles or amphotericin B. Amphotericin B combination with azoles induced synergistic interaction in a range of 11.76-29.41%. Azole combinations and 5-flucytosine combinations with azoles or amphotericin B did not show synergistic interactions. None of the 21 combinations showed antagonistic interactions. Interestingly, 90% of the detected synergism was among the echinocandin-resistant isolates. Disk diffusion assays showed that the inhibition zones produced by antifungal combinations were equal to or greater than those produced by single drugs. The time-killing assay showed the synergistic action of caspofungin combination with fluconazole, voriconazole, and posaconazole, and the amphotericin B-5-flucytosine combination. Furthermore, for the first time, this assay confirmed the fungicidal activity of caspofungin-voriconazole and amphotericin B-5-flucytosine combinations. The combination interactions ranged from synergism to indifference and, most importantly, no antagonism was reported and most of the synergistic action was among echinocandin-resistant isolates.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

Journal of fungi (Basel, Switzerland) - 7(2021), 2 vom: 02. Feb.

Sprache:

Englisch

Beteiligte Personen:

Khalifa, Hazim O [VerfasserIn]
Majima, Hidetaka [VerfasserIn]
Watanabe, Akira [VerfasserIn]
Kamei, Katsuhiko [VerfasserIn]

Links:

Volltext

Themen:

Antifungal synergistic combinations
C. glabrata
Echinocandins
Echinocandins resistance
FKS mutations
Journal Article

Anmerkungen:

Date Revised 16.03.2021

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.3390/jof7020108

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321014375