Synergistic Effects from Combination of Cryptotanshinone and Fosfomycin Against Fosfomycin-Susceptible and Fosfomycin-Resistant Staphylococcus aureus

Purpose: Fosfomycin is now widely used to treat methicillin-resistant S. aureus due to its unique antibacterial activity. However, fosfomycin-resistant S. aureus has rapidly emerged, it is urgent to find new treatments to eliminate fosfomycin-resistant S. aureus infection. The purpose of this study was to analyze the activity of cryptanshinone, a traditional Chinese medicine monomer, in combination with fosfomycin against fosfomycin-sensitive S. aureus (FSSA) and fosfomycin-resistant S. aureus (FRSA). Methods: The MICs of fosfomycin and/or cryptanshinone were determined by agar dilution assay and checkerboard microdilution assay. Furthermore, synergistic effects from fosfomycin and/or cryptanshinone were analyzed by the time-kill assay in vitro. Results: The combination of fosfomycin and cryptotanshinone had a synergistic effect on most (71.43%) of the FRSA and had a partial (28.57%) synergistic effect on a small part. In addition, time sterilization curve verified synergistic activity between cryptanshinone and fosfomycin against FSSA and FRSA, especially when fosfomycin was added for a second time. Conclusion: These data suggest that cryptanshinone combined with fosfomycin could be a novel treatment for FRSA and provide a new direction for the treatment of bacterial infections in the future. Keywords: traditional Chinese medicine, cryptanshinone, fosfomycin, synergistic effect, Staphylococcus aureus