In vitro antimicrobial mechanism of diacerein and potential to reverse MRSE resistance to β-lactams

Staphylococcus epidermidis is the most common pathogens causing ocular infection. With the increase of drug resistance rate, it poses a new challenge to anti-infection treatment. In this study, we analyzed the drug resistance of S. epidermidis isolated from the eye in the past 5 years to guide empirical antibiotics treatment. Then, the MIC and MBC of diacerein against MRSE were detected, and continuous induced resistance experiments confirmed that MRSE not easily induce resistance to diacerein. In addition, it was observed that diacerein induced MRSE cell lysis, increased membrane permeability and resulted in intracellular ROS accumulation. Diacerein does not have toxic effects to HCEC at effective bacteriostatic concentrations. The results of checkerboard assay indicated that the combination of diacerein and β-lactams had additive effect on MRSE. We also observed that diacerein may reverse MRSE resistance to β-lactam drugs by affecting the active efflux system. In conclusion, our results provide strong evidence for the high therapeutic potential of diacerein against MRSE.