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U-78608, a new monocarbam antibiotic, was evaluated for in vitro activity against 312 clinical isolates of aerobic and anaerobic bacteria and subjected to several in vitro biochemical tests characterizing its interactions with beta-lactamases and penicillin-binding proteins (PBPs). The antibacterial activity of the compound was compared directly with those of SQ 83,360 (pirazmonam) and aztreonam. U-78608, SQ 83,360, and aztreonam had generally poor activity against gram-positive aerobic bacteria and anaerobic bacteria. U-78608 demonstrated activity primarily against gram-negative aerobic bacteria, with potency generally comparable to that of SQ 83,360. U-78608 and SQ 83,360 were less active than aztreonam for some gram-negative species; however, both compounds were 8- to 64-fold more active than aztreonam against Acinetobacter species, Pseudomonas aeruginosa, and Pseudomonas maltophilia. All three compounds resisted inactivation by several different beta-lactamases from gram-positive and gram-negative bacteria. Neither U-78608 nor SQ 83,360 exhibited significant inhibition of these enzymes, while aztreonam inhibited beta-lactamases from P. aeurginosa and Klebsiella oxytoca. All three compounds exhibited strong affinity to PBP 3 of Escherichia coli and moderate to negligible affinity to the other E. coli PBPs; quantitative measurements indicated that U-78608 had greater PBP 3 affinity than either SQ 83,360 or aztreonam.

In vitro antibacterial activity and interactions with beta-lactamases and penicillin-binding proteins of the new monocarbam antibiotic U-78608