We assessed antimicrobial susceptibility against 211 Streptococcus pyogenes strains isolated from patients with severe invasive group A streptococcal infections. Overall, 3.8, 1.4, 1.4, and 0.5% of the isolates were resistant to erythromycin, clindamycin, telithromycin, and ciprofloxacin, respectively, and 10.4% had intermediate resistance to ciprofloxacin. All isolates were susceptible to ampicillin and cefotaxime.Streptococcus pyogenes (group A streptococcus) is one of the most common human pathogens. It causes a wide array of infections, the most frequent of which is acute pharyngitis (strep throat). From the late 1980s, streptococcal toxic shocklike syndrome caused by S. pyogenes became a serious problem in both developed and developing countries. Symptoms such as pharyngitis, fever, and pain may suddenly develop, and the disease may progress very rapidly in some patients to softtissue necrosis, acute kidney failure, adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multiorgan failure, leading to shock and death. One approach to treat severe invasive S. pyogenes infections has been to utilize a combination of penicillin and clindamycin. The rationale is that penicillin provides coverage against 100% of S. pyogenes strains and clindamycin has demonstrated greater efficiency in experimental models of necrotizing fasciitis (8). In this study, we tested the antimicrobial susceptibility of 211 S. pyogenes strains isolated from patients with severe invasive group A streptococcal infections.The activity of the Working Group for Group A Streptococci in Japan is based on a network between the National Institute of Infectious Diseases (NIID) and prefectural public health institutes (PHIs); seven branch offices of the reference center are located in the PHIs of Fukushima, Kanagawa, Toyama, Osaka, Yamaguchi, Oita, and Tokyo. Information on streptococcal infections and clinical isolates is sent to the PHIs from 3,041 cooperative hospitals located all over Japan. All of them are collected by NIID. A total of 211 S. pyogenes isolates from 1992 to 2003 were cultured predominantly from sterile body sites of patients with severe invasive group A streptococcal infections (5, 6). All isolates were stored at Ϫ80°C until tests for susceptibility. We analyzed the antimicrobial susceptibility of the isolates by the Etest method for five drugs, ampicillin, cefotaxime, ciprofloxacin, clindamycin, and erythromycin, and by the broth microdilution method as recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (7) for telithromycin. A 0.5 McFarland solution was used to inoculate a Mueller-Hinton agar plate containing 5% sheep blood (Becton Dickinson, Tokyo, Japan) for the Etest method or to inoculate Mueller-Hinton broth containing 5% lysed horse blood (Becton Dickinson) for the broth microdilution method, and the plates were incubated at 37°C in a CO 2 atmosphere. The ATCC 49619 strain of Streptococcus pneumoniae was used as a quality control. The breakpoints of resistance to th...