In vitro antibacterial activity of a new cephalosporin, FR295389, against IMP-type metallo-beta-lactamase-producers

FR295389 is a novel dihydroimidazopyrazolium cephalosporin. Although all previously reported cephalosporins had been ineffective against metallo-beta-lactamase (MBL)-producers, FR295389 showed moderate activity against these strains. The MIC values of FR295389 at which 50% and 90% of 21 clinical isolates of IMP-type MBL-producing Pseudomonas aeruginosa were inhibited were 8.0 and 32 mug/ml, respectively. The kinetic study of IMP-1 MBL showed that the K(m) and the k(cat) values against FR295389 were over 20-fold-higher and 12-fold-lower than those against ceftazidime, respectively, suggesting that FR295389 is a poor substrate for IMP-type MBL. This is the first report of a cephalosporin with activity against IMP-type MBL-producers.