Streptococcus pyogenes (group A streptococcus [GAS]), a major human pathogen (9), has been studied for decades and may give rise to common throat and skin infections as well as to invasive diseases, such as arthritis, septicemia, cellulitis, puerperal fever, necrotizing fasciitis (NF), and streptococcal toxic shock syndrome (STSS) (14). Since the mid-1980s there have been increasing numbers of reports describing severe manifestations of GAS infections; however, the factors underlying the worldwide resurgence of this pathogen remain unknown (20).The M protein, which is encoded by the emm gene, is an important virulence factor and is also an epidemiological marker that is used throughout the world to characterize GAS isolates (5,(21)(22)(23). The type specificity of the M protein, of which more than 100 different types are known, is largely determined by the epitope located in 40 to 50 amino acid residues at the amino terminus (4,16,27). These regions of M proteins have been shown to evoke antibodies that have strong bactericidal activity and that are not likely cross-reactive with

Summary.A total of 16 909 cultures of Streptococcus pyogenes (Lancefield group A) isolated in Britain during 1980-90 were examined for T-and M-protein antigens. One or other M antigen was detected in 92.6 % of the strains. The numbers of isolates of some serotypes, such as M3 and M12, did not show great variation from year-to-year, whereas there were nationwide epidemics, extending over several years, caused by strains of serotypes M1 and M49. Isolates of serotypes M1 and M3 were associated particularly with invasive disease and fatal infections. Representatives of serotypes M80, M81 and the provisional types PT180, PT1658 and PT5757 were isolated most often from cases of pyoderma. Erythromycin resistance was detected in 30 serotypes but one half of all of the resistant isolates belonged to serotype M4.

The molecular population genetics and pathogenic potential of North American and European invasive strains of Streptococcus pyogenes were assessed. Isolates from recent invasive infections and from infections in the 1920s and 1930s were characterized for multilocus enzyme genotype and allelic variation in the gene (speA) that encodes streptococcal pyrogenic exotoxin (SPE) A (scarlet fever toxin). A subset of strains was studied for allelic variation in genes that encode SPE B and streptokinase. All contemporary strains assigned to electrophoretic types (ETs) 1 and 2 that synthesize SPE A have the speA2 and speA3 allelic variants, respectively, and their relative virulence in two mouse models is similar to that of strains of the same ET and M protein types recovered earlier. In contrast, ET 1 and 2 isolates from disease episodes in the 1920s and 1930s contain the speA1 allele. The data suggest there may be temporal and geographic variation in the occurrence of clone--virulence factor allele combinations, an observation that may in part explain fluctuations in disease frequency, severity, and character.

A total of 1,500 recent throat isolates of Streptococcus pyogenes collected between 1996 and 1999 from children throughout France were tested for their susceptibility to erythromycin, azithromycin, josamycin, clindamycin, and streptogramin B. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance, by means of PCR. The clonality of these strains was also investigated by means of serotyping and ribotyping. In all, 6.2% of the strains were erythromycin resistant, and 3.4 and 2.8% expressed the constitutive MLS B and M resistance phenotypes and harbored the ermB and mefA genes, respectively; ermTR was recovered from one isolate which also harbored the ermB gene. Ten serotypes and 8 ribotypes were identified, but we identified 17 strains by combining serotyping with ribotyping. Among the eight ribotypes, the mefA gene was recovered from six clusters, one being predominant, while the ermB gene was recovered from four clusters, of which two were predominant.Penicillin is the drug of choice for the treatment of Streptococcus pyogenes infection. However, for patients sensitive to ␤-lactam antibiotics, and when these drugs fail, macrolides are often the recommended substitute. Penicillin resistance has not yet been described in S. pyogenes, but resistance to erythromycin and related antibiotics has been widely reported (2,3,5,8,10,11,17,20,29,33,43,46). The mechanism of acquired resistance to erythromycin involves a target site modification mediated by a methylase which modifies the 50S ribosomal subunit, leading to the MLS B resistance phenotype encoded by erm genes (25,36,47). Erythromycin resistance due to an efflux mechanism (M phenotype), encoded by mef genes, has recently been described (6,45). While the prevalence of the S. pyogenes resistance to macrolides has been reported worldwide, very few recent data deal with the French situation (1,8). The aims of this study were to assess the macrolide sensitivity of recent throat isolates of S. pyogenes collected from French children, to determine the genetic mechanisms of resistance, and to explore clonality by means of serotyping and molecular methods. MATERIALS AND METHODSBacterial isolates. A total of 1,500 consecutive S. pyogenes isolates were collected between 1996 and 1999 throughout France. They were isolated by swabbing the throats of children, 4 to 17 years old (mean age, 11 years), with pharyngitis. The isolates were identified as S. pyogenes by colony morphology, beta-hemolysis on blood agar, and a commercial agglutination technique (Murex Diagnostics UK).Susceptibility testing. The procedures for susceptibility testing were those recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (30).(i) Detection of erythromycin resistance and determination of resistance phenotypes. Erythromycin-resistant strains were initially identified by the disk diffusion method on Mueller-Hinton agar supplemented with 5% defibrinated horse blood (Diagnostic Pasteur, Marnes la Coquette, France) using 15-g erythrom...

There has been a dramatic increase in the number of detected cases of streptococcal TSS over the 14 years since the first case was recognized here. There was a wide range of invasive forms of infection, a high fatality rate even in fit young adults, and a rapid course from onset to death. There was a high association of TSS with aggressive streptococcal infection producing local tissue necrosis.