Telithromycin activity is reduced by efflux in Streptococcus pyogenes

Objectives: To investigate whether telithromycin is a substrate for efflux pumps in Streptococcus pyogenes. Methods: The distribution of telithromycin MICs was analysed for two distinct collections of Italian (n=486) and Spanish (n=210) S. pyogenes strains. The effect of an efflux mechanism was investigated using [H-3]telithromycin. Results: Telithromycin MIC ranges were <= 0.004-0.06 mg/L (MIC50 and MIC90, 0.01 mg/L) in erythromycin-susceptible strains (lacking both mef and erm genes) and 0.01-1 mg/L (MIC50 and MIC90, 0.5 mg/L) in strains endowed with the M phenotype and expressing the mef(A) gene. A distinct telithromycin efflux was detected in the strains expressing the mef(A) gene, but not in those expressing the erm(B) gene, nor in the susceptible strains lacking mef(A) or erm genes. Efflux reversibility by addition of an inhibiting compound (sodium arsenate) was demonstrated. An msr-like sequence was also found in all strains effluxing telithromycin, but not in the others. Conclusions: This study shows that telithromycin can be removed from S. pyogenes by efflux. That the efflux is related to the presence of the mef(A) gene is demonstrated, but-owing to the increasingly evident complexity of S. pyogenes efflux systems-the possibility that other genes may contribute to the efflux cannot be excluded.