Cooperative Anti‐Candida Effects of Lactoferrin or Its Peptides in Combination with Azole Antifungal Agents

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Abstract
The effects of lactoferrin (LF), an antimicrobial protein secreted in body fluids, and its peptides in combination with azole antifungal agents were investigated by the micro‐broth‐dilution method in a study of Candida albicans. In the case of LF, its pepsin hydrolysate (LFhyd) or the LF‐derived antimicrobial peptide Lactoferricin® B (LF‐B), the concentrations required to inhibit the growth of Candida decreased in the presence of relatively low concentrations of clotrimazole (CTZ). The minimum inhibitory concentration (MIC) of all azole antifungal agents tested was reduced by 1/41/16 in the presence of a sub‐MIC level of each of these LF‐related substances. Polyene and fluoropyrimidine antifungal agents did not show such a combined effect with these LF‐related substances. The anti‐Candida activity of LF or LF‐B in combination with CTZ was shown to be synergistic by checkerboard analysis. These results indicate that LF‐related substances function cooperatively with azole antifungal agents against C. albicans.