Effects of Caspofungin, Tolcapone, and Other FDA-Approved Medications on MRSA Susceptibility to Vancomycin.

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Effects of Caspofungin, Tolcapone, and Other FDA-Approved Medications on MRSA Susceptibility to Vancomycin.

J Glob Antimicrob Resist. 2020 Apr 01;:

Authors: Moore JA, Meakin M, Earl MH, Kummer TM, McAleer JP, Long TE

Abstract
OBJECTIVES: Vancomycin is a first-line antibiotic for invasive infections in human medicine due to methicillin-resistant Staphylococcus aureus (MRSA). Based on the premise that antibiotic combinations can exhibit synergistic and antagonistic interactions, medications used in the treatment of infection and other medical conditions were evaluated for their ability to alter MRSA susceptibility to vancomycin.
METHODS: A chemical library comprised of 1,237 pharmacological agents was evaluated in 96-well plate format for its ability to inhibit MRSA growth in combination with half the minimum inhibitory concentration (MIC) of vancomycin. Caspofungin and tolcapone were further assessed for synergistic potential by isobologram (checkerboard) and flow cytometric analysis. In addition, antibacterial activity spectrum and effects of growth conditions of the two drugs were delineated by MIC determination.
RESULTS: The study identified seventeen nonantibiotic library members with synergistic or additive potential, including caspofungin and tolcapone. Further analyses revealed that the respective medications for invasive candidiasis and Parkinson's disease were bactericidal and bacteriostatic inhibitors of S. aureus growth. Flow cytometric analysis of viability further demonstrated that caspofungin in combination with vancomycin increased MRSA cell death in an additive manner, while tolcapone appeared to suppress the bactericidal action of vancomycin.
CONCLUSIONS: Overall, this proof of concept study concluded that nonantibiotic drugs can alter the pharmacodynamic properties of vancomycin, with potential clinical implications in patients with a MRSA infection receiving a concomitant treatment for another medical condition.

PMID: 32247076 [PubMed - as supplied by publisher]