Enhancement of the in vitro activity of amphotericin B against the biofilms of non-albicans Candida spp. by rifampicin and doxycycline

The in vitro activity of amphotericin B (AMB) alone and in combination with rifampicin (RIF) and doxycycline (DOX) was tested against the biofilms of 30 clinical isolates of non-albicans Candida (NAC) species namely, Candida parapsilosis, Candida krusei and Candida glabrata. The killing activity of AMB at 10 x MIC was significantly increased in combination with either antibiotic. With RIF, the killing activity increased by 20.6, 23.5 and 14% against the biofilms of C. parapsilosis, C. krusei and C. glabrata, respectively; with DOX, the killing activity increased by 30.64, 35.28 and 31.13%, respectively. Pre-exposure of the isolates to the same combinations significantly reduced the number of colonized cells in the biofilms by 20, 25.14 and 13.07% with RIF for C. parapsilosis, C. krusei and C. glabrata, respectively, and by 18.94, 24.52 and 29,15% with DOX, respectively. The data showed that combination of RIF or DOX with AMB enhanced the killing activity of the antifungal agent against biofilms of NAC species. Whether such an effect operates against biofilm-associated infections needs to be clarified by further in vivo studies.