To investigate changes in the antimicrobial susceptibility of Streptococcus pyogenes isolates over a 16-year period, 456 group A streptococci isolates were collected from Chinese pediatric patients among 1993 to 1994 and 2005 to 2008. Susceptibilities to antibiotics were performed using agar dilution methods. The macrolide resistance genes ermB, ermTR, mefA, and tetracycline-resistant gene tetM and the int and xis genes of Tn916 family were detected by polymerase chain reaction. All 456 strains were analyzed by emm typing. Selected strains representing each emm type were further characterized by pulsed-field gel electrophoresis. The resistance rates of erythromycin and clindamycin both significantly increased during the 2 sample periods (79.7% versus 94% for erythromycin and 75.4% versus 96.9% for clindamycin). Telithromycin resistance rate increased from 20.37% to 87.93%. Among the macrolide resistance strains, the rate of strains with the genes int, xis, tetM, and ermB increased with time (16.05% versus 86.91%, P < 0.05). The emm1 and emm12 isolates had high rates of ermB gene, which increased after 16 years (65.2% versus 86.23% for emm1 and 7.7% versus 91.8% for emm12). This study demonstrates the increase in macrolide resistance in S. pyogenes in Chinese children over a 16-year period. The phenomenon may be related not only with the shift in the emm types but also with the change of macrolide-resistant mechanisms. The change of Tn916 family among the isolates may be related with the increased resistance. (C) 2010 Elsevier Inc. All rights reserved.