Among 1,011 recently isolated Streptococcus pyogenes isolates from 10 Central and Eastern European centers, the MICs at which 50% of isolates are inhibited (MIC 50 s) and the MIC 90 s were as follows: for telithromycin, 0.03 and 0.06 g/ml, respectively; for erythromycin, azithromycin, and clarithromycin, 0.06 to 0.125 and 1 to 8 g/ml, respectively; and for clindamycin, 0.125 and 0.125 g/ml, respectively. Erythromycin resistance occurred in 12.3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 g/ml, telithromycin was active against 98.5% of the strains tested.Streptococcus pyogenes strains continue to be penicillin susceptible, but erythromycin resistance has increasingly been reported. A recent Canadian study (10) has documented that 2.1% of S. pyogenes strains collected in 1997 were macrolide resistant. Significant rates of erythromycin resistance have been reported in many countries including Finland, Sweden, Spain, France, and Italy (1,3,6,8,11,12,16,18,20,21,24). In the United States, it has been assumed that the rate of erythromycin resistance is low (14, 15). However, a recent study has reported erythromycin resistance rates of 32% among isolates from specimens from patients with invasive disease and 9% among isolates from cultures of throat swab specimens isolated between 1994 and 1995 in the San Francisco, California, area (25).For S. pyogenes isolates from most areas tested, macrolide resistance is mediated by the mef(A) gene (23), making the isolates resistant to 14-and 15-membered-ring macrolides but susceptible to 16-membered-ring macrolides and clindamycin. Erm(A) [subclass erm(TR)] has also been described (21); strains containing erm(A) are usually inducibly resistant to 14-and 15-membered-ring macrolides but are susceptible to 16-membered-ring macrolides and lincosamides. The erm(B) gene has also been described, with strains that contain this gene being resistant to macrolides and lincosamide (6,10,11,16).Telithromycin is a ketolide (9, 13, 19) with low MICs for erythromycin-susceptible and -resistant S. pyogenes strains except those carrying erm(B). To understand macrolide susceptibility in areas where high rates of drug-resistant pneumococcci have been described, Central and Eastern Europe (2), we tested the activities of telithromycin, erythromycin, azithromycin, clarithromycin, and clindamycin against 1,011 isolates of S. pyogenes. Levofloxacin was tested as the representative fluoroquinolone.Strains were consecutively obtained from clinical isolates recovered during 1999 and 2000 and were screened by the bacitracin disk method. Organisms were frozen at all collection sites except Warsaw (where swabs in Amies transport medium were used) and were transported on dry ice to Hershey Medical Center, where they were stored frozen in double-strength skim milk (Difco Laboratories, Detroit, Mich.) at Ϫ70°C until use. The identities of the organisms were confirmed by colonial morphology, bacitracin testing, beta-hemolys...