Berberine and Itraconazole Are not Synergistic in Vitro against Aspergillus fumigatus Isolated from Clinical Patients

The incidence of Aspergillus fumigatus infections has become more frequent as a consequence of widespread immunosuppression. At present, the number of available antifungal agents in the clinic is limited, and most of them, such as itraconazole (ICZ), are toxic and show resistance. Berberine (BER) is a plant alkaloid used in the clinic mainly for alimentary infections. We have used BER and ICZ to measure in vitro resistance in A. fumigatus isolated from clinical patients. The minimum inhibitory concentration ranges of BER and ICZ were 4-256 and 0.031-0.250 mu g/mL, respectively. In addition, against A. fumigatus IFM 40808 strain, the MIC50 values of BER and ICZ were 8 and 0.125 mu g/mL. Using this strain, we compared the giant colonies with or without BER, and concluded that BER could restrain A. fumigatus mycelial growth and conidial pigment production. Combinations of the two drugs were also tested by the checkerboard assay to identify any functional interactions between them. Thirty-two out of 42 isolates had FICI values > 4.0, indicating that two drugs were mutually antagonistic. In conclusion, it is not advised that BER and ICZ be used in the clinic at the same time. Our results indicated that BER may inhibit A. fumigatus through the ergosterol biosynthesis pathway, like ICZ.