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Benzoxazine series of histidine kinase inhibitors as potential antimicrobial agents with activity against enterococci
Müller-Premru, Manica ...
Background: Antibacterial activity of three members of a benzoxazine series ofhistidine kinase inhibitors (4a, 4b and 6) was studied on standard strains, and with 4b also on clinical isolates of ...enterococci. Methods: Susceptibility to each compound was tested using a broth macrodilution method with a range ofdilutions from 0.016 to 128 g/ml on four standard strains (Escherichia coliATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299). Results: Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 g/ml, S. aureus ATCC 43300 at 32 g/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 g/ml, while 4a and 6did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5-16 g/ml. Conclusions: Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.
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