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-lincosamide-streptogramin B phenotype and the ermB genotype. Pneumococcal strains had telithromycin minimum inhibitory concentrations (MICs) ranging between 2 and 8 microg/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.


CONCLUSIONS
The killing by telithromycin of S. pneumoniae isolates having an ermB resistance determinant and a telithromycin MIC of > or =2 microg/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.
Al-Lahham
Adnan
A
Institute of Medical Microbiology, National Reference Centre for Streptococci, Aachen, Germany.
Reinert
Ralf René
RR
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005838:Genotype; D048628:Ketolides / Q000494:pharmacology*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin