Antibacterial activity in vitro of tigemonam, a new oral monobactam

Using a broth microdilution method, the antibacterial activity of tigemonam, a novel oral monobactam, was evaluated against 217 gram-negative aerobes freshly isolated from clinical specimens. Reference antibiotics were amoxicillin, amoxicillin-sulbactam, cephalexin, cefaclor, norfloxacin, and co-trimoxazole. At a concentration of less than or equal to 8 mg/L, tigemonam inhibited 88% of the members of the Enterobacteriaceae family. Its activity was poor against the nonfermenter pathogens. In comparison with the other drugs, tigemonam generally exhibited superior antibacterial activity (with the exception of norfloxacin, which showed similar potency against the strains tested). Minimum bactericidal concentrations and time-kill determinations indicated that tigemonam showed remarkable bactericidal activity, with a 9% reduction in colony-forming units after 2 h at a dose corresponding to fourfold its minimum inhibitory concentration. When tigemonam was used in combination with netilmicin and amikacin against susceptible representative isolates of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Escherichia coli, a synergistic effect was obtained.