Fluconazole, caspofungin, voriconazole in combination with amphotericin B

Combined antifungal therapy has been suggested to enhance the efficacy and reduce the toxicity of antifungal agents. The aim of the study was to investigate the in vitro synergistic activity of caspofungin, voriconazole, and fluconazole with amphotericin B against ten isolates of Candida parapsilosis and Candida albicans strains which were resistant to azoles or amphotericin B. Three different antifungal combinations (amphotericin B [AP] — caspofungin [CS], amphotericin B — fluconazole [FL], and AP — voriconazole [VO]) were evaluated for in vitro synergistic effect by the microdilution checkerboard and E-test methods. For the majority of strains, the combination test showed indifferent activity. Via the E-test method, synergistic activity was seen in 3 strains in response to AP-CS combination treatment and in one strain after administration of AP-FL; however, no synergy was observed in response to combination treatment with P-VO. Antagonistic activity was the result in 1 strain treated with AP-CS as well as in 6 strains treated with AP-FL and AP-VO combinations. Via the microdilution test, no synergistic activity was seen after treatment with all 3 combinations. Antagonistic activity was the result in 2 strains with AP-CS, in 6 strains with AP-VO and in 5 strains with AP-FL combinations. Agreement between the checkerboard and E-test methods was observed to be approximately 72%. These combinations may be used in the case of antifungal resistance.