Background: Candida albicans biofilms display increased levels of resistance to most antifungal agents. Here we have evaluated whether combination treatment of in vitro formed biofilms is superior to application of a single antifungal agent. Methods: C. albicans strain 3153A biofilms were formed on 96 well microtiter plates. Biofilms in plates were treated with checkerboard combinations of fluconazole (FLU), amphotericin B (AMB) and caspofungin (CSP), and incubated for 48 h. Sessile minimum inhibitory concentrations (SMIC80s) were calculated using a colorimetric XTT-reduction assay that measures metabolic activity of sessile cells within the biofilms. We also used checkerboard combinations of the same antifungal agents under planktonic conditions to determine MICs using an NCCLS broth microdilution method. Results: SMIC80 values for FLU, AMB, and CSP alone were >64, 0.5 and 0.5 Âµg/ml respectively. Combinations of CSP with AMB showed additive effect against C. albicans biofilms. Addition of FLU to AMB did not alter AMB activity against biofilms (indifference). However, FLU showed an antagonistic effect on CSP activity against biofilms, a detrimental effect that was not detected under planktonic conditions where CSP MIC values were not affected by addition of FLU. Conclusions: AMB and CSP combinations showed increased activity against C. albicans biofilms, which may prove valuable in the therapy of these difficult to treat infections. In contrast, FLU inhibits CSP activity against C. albicans biofilms, an effect which is not seen under planktonic conditions, indicating that different resistance mechanisms may be operational under biofilm and planktonic-growing conditions.
Full conference title:
42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 42nd