In vitro analyses of the combination of high-dose doxycycline and antifungal agents against Candida albicans biofilms.
Academic Article
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
The potential of antifungal agents used as antimicrobial lock therapy (ALT) for the conservative management of catheter-related candidemia has not been fully defined. We sought to determine the antifungal effect of high-dose doxycycline (DOX), alone or in combination with standard concentrations of amphotericin B (AMB), caspofungin (CAS) or fluconazole (FLC), against biofilms formed by Candida albicans in vitro. DOX alone (at 2048 microg/mL and 1024 microg/mL) demonstrated up to an 85% reduction of the metabolic activity of the C. albicans biofilm. Regardless of the concentration tested, FLC alone showed minimal activity (mean 22.9% reduction) against the C. albicans biofilm. When DOX 2048 microg/mL was used in combination with FLC, antifungal activity also increased up to 85%, suggesting an additive effect. DOX 128 microg/mL in combination with FLC demonstrated synergy (mean 58.3% reduction). The combination of DOX 2048 microg/mL or 512 microg/mL and AMB was superior to AMB alone at low concentrations (0.25-0.03125 microg/mL). However, DOX 128 microg/mL was antagonistic in combination with low concentrations of AMB. Maximal efficacy against the biofilm was observed with CAS at 8-0.25 microg/mL compared with FLC and AMB alone. A paradoxical effect (PE) occurred with CAS at 16 microg/mL, which showed a marked reduction in antifungal activity compared with lower concentrations of CAS. CAS at 16 microg/mL in combination with either DOX 2048 microg/mL or 512 microg/mL resulted in attenuation of the PE. These findings suggest that a high-dose DOX-based ALT strategy in combination with traditional antifungal agents may be useful for the treatment of C. albicans biofilms.
