Synergistic Effect between Cryptotanshinone and Antibiotics against Clinic Methicillin and Vancomycin-Resistant Staphylococcus aureus

Cryptotanshinone (CT), a major tanshinone of medicinal plant Salvia miltiorrhiza Bunge, demonstrated strong antibacterial activity against clinic isolated methicillin and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) in this experiment. The CT was determined against clinic isolated MRSA 1-16 with MIC and MBC values ranging from 4 to 32 and 8 to 128  μ g/mL; for MSSA 1-2 from 16 to 32  μ g/mL and 64 to 128  μ g/mL; for VRSA 1-2 from 2 to 4  μ g/mL and 4 to 16  μ g/mL, respectively. The range of MIC50 and MIC90 of CT was 0.5-8  μ g/mL and 4-64  μ g/mL, respectively. The combination effects of CT with antibiotics were synergistic (FIC index <0.5) against most of tested clinic isolated MRSA, MSSA, and VRSA except additive, MRSA 4 and 16 in oxacillin, MRSA 6, 12, and 15 in ampicillin, and MRSA 6, 11, and 15 in vancomycin (FIC index < 0.75-1.0). Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 2-6 h of treatment with the 1/2 MIC of CT, regardless of whether it was administered alone or with ampicillin, oxacillin, or vancomycin. The results suggest that CT could be employed as a natural antibacterial agent against multidrug-resistant pathogens infection.