Abstract
Haernophilus inituenzae 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 geomettic 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 PBP3 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.
