A new research paper of interest:
A novel mechanism of action of ketoconazole: inhibition of the Nora Efflux Pump system and biofilm formation in multidrug-resistant Staphylococcus aureus
Background: The rapid emergence of antimicrobial resistance among Gram-positive organisms, especially staphylococci, has become a serious clinical challenge. Efflux machinery and biofilm formation are considered two of the main causes of antimicrobial resistance and therapy failure.
Aim: Our study aims to evaluate the antibiofilm and efflux pump inhibitory activity of the antifungal ketoconazole against multidrug-resistant (MDR) Staphylococcus aureus.
Methods: Ketoconazole was tested for its effect on the following: minimum inhibitory concentrations (MICs) of ciprofloxacin, norfloxacin, levofloxacin, and ethidium bromide (EtBr) by the broth microdilution method, the efflux of EtBr by NorA-positive MDR S. aureus, and the relative expression of NorA, NorB, and NorC efflux pump genes. Docking studies of ketoconazole were performed using 1PW4 (glycerol-3-phosphate transporter from Escherichia coli which was the representative structure from the major facilitator superfamily).
Results: Ketoconazole significantly decreased the MICs of levofloxacin, ciprofloxacin, norfloxacin, and EtBr (a substrate for efflux pump) by 8 to 1024-fold (P
Conclusion: The findings showed that the antifungal ketoconazole has no antibacterial activity but can potentiate the activity of the fluroquinolones against MDR S. aureus via inhibiting efflux pump and biofilm formation in vitro.
The reference is:
Abd El-Baky RM, Sandle T, John J, Abuo-Rahma GE, Hetta HF (2019) A novel mechanism of action of ketoconazole: inhibition of the NorA efflux pump system and biofilm formation in multidrug-resistant Staphylococcus aureus, Infection and Drug Resistance, 12: 1703-1708
To access see: https://www.researchgate.net/publication/333679872_A_novel_mechanism_of_action_of_ketoconazole_inhibition_of_the_NorA_efflux_pump_system_and_biofilm_formation_in_multidrug-resistant_Staphylococcus_aureus
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
