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.
Takeda
Shinobu
S
Pharmacology Research Labs, Astellas Pharma Inc., 1-6 Kashima 2-Chome, Yodogawa-ku, Osaka, Japan. shinobu.takeda@jp.astellas.com
Ikeda
Fumiaki
F
Hatano
Kazuo
K
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D002511:Cephalosporins / Q000737:chemistry* / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004269:DNA, Bacterial; C529285:FR 295389; C409201:beta-lactamase IMP-1; D001618:beta-Lactamases