In vitro antibacterial activity of a new quinolone, NM394

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Abstract
NM394 is a new 6-fluoroquinolone antibacterial agent with a tricyclic structure which has a bridge that connects the N-1 and C-2 positions of the quinolone. The antibacterial activity of NM394 against clinical isolates of staphylococci, streptococci, enterococci, members of the family Enterobacteriaceae, and Pseudomonas aeruginosa was equal to or one-half that of ciprofloxacin. NM394 was as active as ofloxacin against gram-positive bacteria and was two to eight times more active against gram-negative bacteria, including P. aeruginosa. NM394 was two to eight times more active than enoxacin against gram-positive and gram-negative bacteria. The MICs of NM394 against Escherichia coli and P. aeruginosa at pH 5.5 were reduced 4 to 16 times compared with those at pH 7.0. Ciprofloxacin, ofloxacin, and enoxacin were 2 to 32 times less active against these two bacteria and Staphylococcus aureus at an acidic pH than they were at pH 7.0. In the presence of 5 mM Mg2+, the MICs of all of these drugs increased 2 to 32 times, but they were only slightly affected by 5 mM Ca2+, type of medium, serum, or size of inoculum. NM394 showed potent bactericidal activity and inhibited the supercoiling activity of E. coli DNA gyrase. The in vitro antibacterial profile of NM394 is similar to that of other 6-fluoroquinolones.