DETERMINATION OF BROTH MICRODILUTION MINIMUM INHIBITORY CONCENTRATIONS OF ANTIFUNGALS COMPLEXED OR NOT WITH CYCLODEXTRIN FOR Candida spp.

Nystatin (Nys) and chlorhexidine (Chx) demonstrate high effectiveness in inhibiting Candida spp. These drugs are almost insoluble in water and their bitter taste can produce side effects. Inclusion complexes with cyclodextrins have been developed to enhance stability and optimize the antimicrobial activity with few side effects. This study evaluated the in vitro activity of Nys and Chx complexed or not with β-cyclodextrin (βCD) for nine Candida spp. strains. Inclusion complexes 1:1 Nys:βCD and 1:2 Chx:βCD were obtained by freeze-drying. Nys, Chx, Nys:βCD, Chx:βCD, and βCD were tested against C. albicans (ATCC 14053), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata, C. guilliermondii, C. tropicalis, and three C. auris isolates, using EUCAST reference susceptibility broth microdilution method to determine their minimum inhibitory concentrations (MIC). All strains were highly susceptible to the evaluated antifungals, complexed or not, and to the βCD. Nys presents the highest activity against C. parapsilosis (MIC80=0.125 µg/mL) and C. glabrata (MIC80=0.25 µg/mL). Intermediate concentration values were necessary against C. guilliermondi, C. tropicalis, C. albicans, and C. auris isolate #03 (MIC80=0.5 µg/mL), and higher concentration values were necessary against C. auris isolates #01 and #02, and C. krusei (MIC80=1 µg/mL). For Chx, the highest susceptibility was observed against C. guilliermondi, C. tropicalis, C. auris isolate #02, C. krusei, and C. parapsilosis (MIC80=4 µg/mL). Values 2-fold higher (MIC80=8 µg/mL) of Chx were necessary to kill C. glabrata, C. albicans, and C. auris isolates #01 and 03. MIC80 of 1:1 Nys:βCD was 1 µg/mL against C. parapsilosis, 4 µg/mL against C. glabrata, C. guilliermondi, C. tropicalis, C. albicans, C. auris isolate #01, and C. krusei, and 8 µg/mL against C. auris isolates # 02 and #03. MIC80 of 1:2 Chx:βCD was 4 µg/mL against C. guilliermondi, C. krusei, and C. parapsilosis, 8 µg/mL against C. glabrata, C. tropicalis, and C. albicans, and 16 µg/mL against all C. auris isolates. MIC80 of βCD was 32 µg/mL for all Candida spp. The susceptibility of Candida spp. was not higher for 1:1 Nys:βCD compared with Nys, but lower concentrations of Chx when complexed with βCD were necessary to inhibit Candida spp. growth.