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 mug/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 mug/ml. No SBA was observed against isolates with MICs of 4.0 or 8.0 mug/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 mug/ml or less.