Purpose: To evaluate the antimicrobial and resistance-reversal activities of seven phenothiazine derivatives against one standard methicillin-sensitive and ten methicillin-resistant
Staphylococcus aureus
(MRSA) strains originating from human infections.
Methods: Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and oxacillin was investigated using Checkerboard (microbroth dilution) technique.
Results: We found that all
S. aureus strains, regardless of their susceptibility to oxacillin, were inhibited by phenothiazines at a concentration of 8 - 256 μg/mL, with thioridazine being the most potent inhibitory agent. Phenothiazines at sub-inhibitory concentrations lowered the MIC of oxacillin from 256 to 2 μg/mL, which is a clinically significant level. The highest number of synergistic combinations, i.e., fractional inhibitory concentration (FIC) index less than 0.5, was seen with chlorpromazine and perphenazine. However, thioridazine reversed antibiotic resistance at a concentration as low as 4 μg/mL.
Conclusion: Although synergy was observed at concentrations higher than those that phenothiazines usually attain in vivo, the potential offered by non-antibiotics justifies further animal experiments as well as clinical trials to establish their clinical relevance.
