Vol.53 No.2 February 2005
Classification of β-lactam agents based on antibacterial activity for Haemophilus influenzae with penicillin-binding protein 3 mutations
1)Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd.,
760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa, Japan
2)Tokyo Branch, Pharmaceutical Marketing Division, Meiji Seika Kaisha, Ltd.
3)Laboratory of Infectious Agents Surveillance, Kitasato Institute for Life Sciences
Abstract
Haemophilus influenzae numbering 215 clinical isolates were classified into 6 groups based on amino acid mutation in penicillin-binding protein 3, associated with β-lactam resistance. MICs of 24 β-lactam agents were determined for these isolates, and geometric mean MICs were determined for each of six PBP 3 mutation groups. Cluster analysis was conducted for these 24 β-lactam agents using geometric mean MICs and agents were classified into three clusters reflecting antibacterial activity against H. influenzae including PBP 3 substituted strains. Agents with strong activity against H. influenzae, i. e., meropenem, tazobactam/piperacillin, and cefditoren, were classified into the same cluster. Increased ratios of geometric mean MICs involved with PBP 3 mutations were determined and modified as variables for cluster analysis. From the result of this analysis, many of β-lactam agents were classified into several clusters reflecting their chemical skeletons. Side chains at the C-7 position may be related to the clustering of cephalosporins. Cefditoren was uniquely ranked in this evaluation because its antibacterial activity would be barely affected by PBP 3 mutations. Cluster analysis based on drug resistance mechanisms is thus useful for evaluating β-lactam agents.
Key word
Haemophilus influenzae, penicillin-binding protein 3, β-lactam, clustering
Received
September 17, 2004
Accepted
January 5, 2005
Jpn. J. Chemother. 53 (2): 121-127, 2005
