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Interactions between triazoles and echinocandins against Candida albicans planktonic cells and biofilms

Abstract number: P1813

Chatzimoschou A., Simitsopoulou M., Antachopoulos C., Stergiopoulou T., Georgiadou E., Walsh T.J., Roilides E.

Objectives:Candida albicans (CA) is an important cause of endovascular infections that are related to foreign bodies. As antifungal triazoles are commonly administered concurrently with echinocandins, and as triazoles have been previously shown to have antifungal activity against Candida biofilms (BF) only at very high concentrations (>256 mg/L, Katragkou et al, AAC 2008; 52: 357), we studied the antifungal activity of voriconazole (VRC) against CA BF or planktonic cells (PL) in combination with two echinocandins, caspofungin (CAS) or anidulafungin (AND). Similarly, we studied the activity of posaconazole (PSC) in combination with the same two echinocandins.

Methods: CA-M61, a well-documented BF-producing CA strain, was grown in RPMI at 5×105 blastoconidia/mL on silicone disks in 96-well plates at 37°C for 48 h in order to produce BF. PL were grown in YNB at 37°C for 24 h. PL and BF were then incubated for 24 h with 2-fold dilutions of VRC or PSC (16–1024 mg/L), and CAS or AND (0–16 mg/L) alone or concurrently, VRC/PSC with CAS/AND in a checkerboard format. Fungal damage induced by antifungal agents to PL and BF was assessed by XTT assay. The interactions between VRC+AND, VRC+CAS, PSC+AND and PSC+CAS were analyzed using the Bliss model (Meletiadis et al, Med. Mycol. 2005; 43: 133). Synergy, antagonism or indifference was concluded when the observed fungal damage was significantly higher than, lower than or equal to the expected damage, respectively.

Results: Against PL, a synergistic interaction was observed between 32–128 mg/L of PSC combined with 0.008–0.25 mg/L of CAS. By contrast, antagonism was observed when either of the two triazoles was combined with AND at the following concentration ranges: 128–1024 mg/L PSC + 0.03–0.5 mg/L AND, 16–512 mg/L VRC + 0.008–0.015 mg/L AND or 128–512 mg/L VRC + 0.03–0.25 mg/L AND. Against BF, all drug combinations demonstrated indifferent interactions.

Conclusions: The differential interactions of synergy or antagonism between triazoles and echinocandins observed against CA PL become indifferent in the presence of CA BF.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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