Antibiotics (Nov 2022)

Synergistic Interaction of Caspofungin Combined with Posaconazole against <i>FKS</i> Wild-Type and Mutant <i>Candida auris</i> Planktonic Cells and Biofilms

  • Noémi Balla,
  • Fruzsina Kovács,
  • Bence Balázs,
  • Andrew M. Borman,
  • Aliz Bozó,
  • Ágnes Jakab,
  • Zoltán Tóth,
  • Ola Kobaissi,
  • László Majoros,
  • Renátó Kovács

DOI
https://doi.org/10.3390/antibiotics11111601
Journal volume & issue
Vol. 11, no. 11
p. 1601

Abstract

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Candida auris is a potential multidrug-resistant pathogen able to cause biofilm-associated outbreaks, where frequently indwelling devices are the source of infections. The number of effective therapies is limited; thus, new, even-combination-based strategies are needed. Therefore, the in vitro efficacy of caspofungin with posaconazole against FKS wild-type and mutant Candida auris isolates was determined. The interactions were assessed utilizing the fractional inhibitory concentration indices (FICIs), the Bliss model, and a LIVE/DEAD assay. Planktonic minimum inhibitory concentrations (pMICs) for the caspofungin–posaconazole combination showed a 4- to 256-fold and a 2- to 512-fold decrease compared to caspofungin and posaconazole alone, respectively. Sessile minimum inhibitory concentrations (sMICs) for caspofungin and posaconazole in combination showed an 8- to 128-fold and a 4- to 512-fold decrease, respectively. The combination showed synergy, especially against biofilms (FICIs were 0.033–0.375 and 0.091–0.5, and Bliss cumulative synergy volumes were 6.96 and 32.39 for echinocandin-susceptible and -resistant isolates, respectively). The caspofungin-exposed (4 mg/L) C. auris biofilms exhibited increased cell death in the presence of posaconazole (0.03 mg/L) compared to untreated, caspofungin-exposed and posaconazole-treated biofilms. Despite the favorable effect of caspofungin with posaconazole, in vivo studies are needed to confirm the therapeutic potential of this combination in C. auris-associated infections.

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