Minocycline and Fluconazole Have a Synergistic Effect Against Both and .

In recent decades, the incidence of infection, which causes cryptococcosis, has consistently increased. Fluconazole (FLU) is frequently used in the treatment of this disease, mainly in the immunocompromised population, and long-term therapy usually produces drug resistance. Research on antifungal sensitizers has gained attention as a possible means of overcoming this drug resistance. Minocycline (MINO) has an inhibitory effect on FLU-resistant , and the combination of MINO and FLU has a synergistic effect on FLU-resistant . A synergistic effect of MINO/FLU has been reported against , but this effect has not been evaluated on FLU-resistant isolates. This study aimed to investigate the interaction of MINO and FLU against FLU-resistant both and . We found that the combination of MINO and FLU had a synergistic effect on FLU-resistant . For all FLU-resistant strains, the minimum inhibitory concentration (MIC) of FLU decreased significantly when used in combination with MINO, dropping from >128 μg/ml down to 4-8 μg/ml. Additionally, MINO and FLU had a synergistic effect on both susceptible and resistant biofilms, in which the MIC of FLU decreased from >256 μg/ml down to 4-16 μg/ml. Compared with FLU alone, the combination of MINO with FLU prolonged the survival rate of larvae infected with FLU-resistant , and also significantly decreased the fungal burden of infected larvae and reduced the tissue damage and destruction caused by FLU-resistant . These findings will contribute to the discovery of antifungal agents and may yield a new approach for the treatment of cryptococcosis caused by FLU-resistant .