M-1570. Evaluation of Antifungal Drug Combinations against Candida albicans (CA) Biofilms
Session: Poster Session: Fungal Biofilms
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: CA biofilm-related infections are resistant to azoles. We aimed to investigate the activities of two triazoles against CA biofilms (BF) concurrently or after treatment with two echinocandins. Methods: CA-M61, a BF-producing CA, was used for BF growth by incubating 5x10^5 blastoconidia/mL on silicone elastomer disks in 96-well plates at 37°C under shaking for 48 h. Mature BF were co-incubated for 24 h with 2-fold dilutions of posaconazole (PSC) or voriconazole (VRC) at 64-512 mg/L, and caspofungin (CAS) or anidulafungin (AND) at 0-16 mg/L alone or concurrently, PSC with CAS and VRC with AND, using a checkerboard microdilution method. In addition, equal CA inoculum was incubated in the presence of 2-fold dilutions of CAS or AND (0-0.064 mg/L) for 48 h to form BF and were then incubated for further 24 h with VRC or PSC (64-512 mg/L), respectively. BF formation and damage was assessed by XTT assay. Statistical analysis was performed using ANOVA with Dunnett test. The interactions between PSC+CAS and VRC+AND were analyzed using the Bliss model. Synergy, antagonism or indifference were defined when the observed BF damage was significantly higher than, lower than or equal to the expected damage, respectively. Results: After co-incubation of mature BF with PSC+CAS or VRC+AND, the combined BF damage was indifferent. In contrast, while PSC or VRC at <1024 mg/L did not achieve substantial BF damage, BF formation in the presence of echinocandins at 0.008-0.064 mg/L and subsequent addition of 256 or 512 mg/L of PSC or VRC to the grown BF showed significant increase in BF damage (CAS+PSC, p<0.05; AND+VRC, p<0.01). Conclusion: Combined effects of PSC+CAS or VRC+AND are indifferent against CA BF. Impaired formation of BF in the presence of sub-MICs of echinocandins leads to increased BF damage by subsequent treatment with azoles. These findings may help in further studies on therapeutic modalities of BF-associated infections.
Aspasia Katragkou, MD1, Athanasios Chatzimoschou2, Charalampos Antachopoulos, MD, PhD1, Elpiniki Georgiadou3, Emmanuel Roilides, PhD4, Maria Simitsopoulou, PhD1, Theodouli Stergiopoulou, MD5, Thomas Walsh, MD, FIDSA6 and  A. Katragkou, None., (1)Aristotle Univ., Thessaloniki, Greece, (2)Aristotle University, Thessaloniki, Greece, (3)Aristotle University od Thessaloniki, (4)Hippokration Hospital, Thessaloniki, Greece, (5)NCI, Bethesda, MD, (6)National Cancer Institute, Bethesda, MD

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