Use of a Sensitive Chemiluminescence-Based Assay to Evaluate the Metabolic Suppression Activity of Linezolid on Methicillin-Resistant Staphylococcus aureus Showing Reduced Susceptibility to Vancomycin

Recently, strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VCM) have been clinically isolated. The antibacterial activity of a new drug, linezolid (LZD), in such a strain was evaluated by measuring bacterial metabolic activity. A total of 73 MRSA strains having various susceptibilities to VCM were subjected to a novel and highly sensitive chemiluminescence-based assay. LZD MIC in the tested strains, measured by the microbroth dilution method, was within the range 1-4 mg/l (mostly <= 2 mg/l), except for one LZD-resistant strain (NRS127; MIC=7 mg/l), and showed no correlation with VCM resistance. The chemiluminescence assay demonstrated that bacterial metabolic activity was strongly suppressed with increasing LZD concentration. The chemiluminescence intensity curve had a low baseline activity without tailing in most strains. The present results suggest that LZD has strong antibacterial activity against MRSA strains, and would be effective for treatment of infections that are poorly responsive to VCM. The chemiluminescence assay facilitated sensitive and discriminative susceptibility testing within a relatively short time.