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This study compared the in vitro activity of telithromycin with that of azithromycin against 438 Streptococcus pyogenes and 198 Streptococcus pneumoniae, isolated over the period 2005–2007 from specimens of different human origin obtained in three Piemonte Region's hospitals.The determination of antimicrobial activity was evaluated by the microdilution broth method and the erythromycin-resistant (Ery-R) phenotypes by the triple-disc test. Exactly 78·8% of S. pyogenes and 69·2% of S. pneumoniae were erythromycin-susceptible (Ery-S). Concerning S. pyogenes, telithromycin was active against M and inducible MLSB, subtype-C, phenotypes but not against constitutive MLSB strains. Telithromycin acted well against all S. pneumoniae, irrespective of their mechanism of macrolide-resistance. On the contrary, the Ery-R isolates, both S. pyogenes and S. pneumoniae, were resistant to azithromycin.Our results indicate that macrolide resistance in streptococci still persist in northwest Italy (21·2% of S. pyogenes and 30·8% of S. pneumoniae) and that telithromycin is confirmed as being extremely active even against recent clinical Ery-R streptococcal isolates.The present study emphasizes that an active surveillance of the phenotype distribution and antibacterial resistance in streptococci is essential in guiding the effective use of empirical treatment option for streptococcal infections, also at regional level.