Serum bactericidal activity of extended-release clarithromycin against macrolide-resistant strains of Streptococcus pneumoniae

STUDY OBJECTIVE: To investigate the serum bactericidal activity (SBA) over time of extended-release clarithromycin against moderately resistant strains of Streptococcus pneumoniae. DESIGN: Prospective, single-dose pharmacodynamic study. SETTING: University-affiliated research center. SUBJECTS: Eleven healthy male volunteers. INTERVENTION: All volunteers received a single dose of extended-release clarithromycin as two 500-mg tablets, and blood samples were obtained at 0, 2, 6, 12, and 24 hours after administration of the dose. MEASUREMENTS AND MAIN RESULTS: For each blood sample, a serum bactericidal titer (SBT) was determined against S. pneumoniae strains with minimum inhibitory concentrations (MICs) of 0.5, 1.0, 2.0, 4.0, and 8.0 microg/ml to clarithromycin. The median SBT was determined for each time period. The extended-release formulation of clarithromycin exhibited SBA for 24 hours against pneumococcal strains with MICs of 0.5, 1.0, and 2.0 microg/ml. No SBA was observed against isolates with MICs of 4.0 or 8.0 microg/ml. CONCLUSION: The extended-release formulation of clarithromycin, taken once/day, will provide SBA for 24 hours against strains of S. pneumoniae with MICs of 2.0 microg/ml or less.