Tigemonam, a new oral monobactam, was at least as active as aztreonam or carumonam against clinical isolates of Enterobacteriaceae (MIC90:0.06-16 mg/l). Tigemonam was very stable in the presence of classical plasmid mediated beta-lactamases but its MICs were increased (4-256 mg/l) in the presence of new broad-spectrum plasmid mediated beta-lactamases (either TEM of SHV derivatives). Increased MICs (0.25-8 mg/l) were also observed for different isogenic mutants of Enterobacteriaceae, which either produced high levels of chromosome-encoded cephalosporinases, or had a permeability defect.