Time-kill kinetics of Streptococcus pneumoniae with reduced susceptibility to telithromycin

Background: Telithromycin is a new ketolide increasingly used in Europe and the United States. Only very few telithromycin-resistant isolates have been described to date. Methods: The anti-pneumococcal activity of telithromycin was determined against four clinical isolates of Streptococcus pneumoniae with reduced susceptibility to telithromycin by time-kill methodology. Results: All four telithromycin non-susceptible strains had the constitutive macrolide-lincos-amide-streptogramin B phenotype and the ermB genotype. Pneumococcal strains had telithromycin minimum inhibitory concentrations (MICs) ranging between 2 and 8 mu g/ml. Mulitlocus sequence typing and serotyping showed three isolates to harbour the identical serotype (serotype 14) and sequence type (sequence type 143) indicating a genetic relatedness of strains. Telithromycin was only bactericidal against the isolates with telithromycin resistance, with 4 - 8 times the MIC after 24 h. Conclusion: The killing by telithromycin of S. pneumoniae isolates having an ermB resistance determinant and a telithromycin MIC of >= 2 mu g/ml is slow. Achievable concentrations in serum, alveolar macrophages and epithelial lining fluid are below the concentrations which are necessary for bactericidal killing of highly telithromycin-resistant strains. Copyright (c) 2007 S. Karger AG, Basel