A total of 301 German pediatric group A streptococcus isolates were screened for the presence of macrolide resistance and the fibronectin binding protein F1 gene (prtF1) encoding an adhesin and cell invasiveness protein. The prtF1 gene was present significantly more often among macrolide-resistant isolates. The majority of these were not clonally related.Group A streptococcal (GAS) (Streptococcus pyogenes) tonsillopharyngitis is one of the most common bacterial infections in children. Resistance to penicillin has not been described, but many European countries have recently experienced an increase in macrolide resistance (2,6,17). Macrolide resistance mechanisms include target site modification, leading to resistance to macrolides, lincosamides, and streptogramin B (MLS phenotype), or an efflux mechanism mediating resistance only to 14-and 15-membered macrolides (M phenotype) (11). Recently, an association between erythromycin resistance and cell invasiveness, as demonstrated by the presence of the fibronectin binding protein F1, encoded by the prtF1 gene, has been observed (8,14). In addition, Cocuzza et al. recently demonstrated selection for prtF1-positive strains after -lactam therapy (5). Here, we investigated pediatric GAS strains in order to generate data on antibiotic resistance rates in the pediatric population of a southwestern region of Germany. Moreover, the association between the prtF1 gene and macrolide and tetracycline resistance was investigated.From June 1999 through January 2003, 301 GAS isolates were collected at the Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany, from in-and outpatients Ͻ16 years old. GAS were grown mostly from throat swabs. Duplicate isolates from the same patient were excluded. All isolates were tested for susceptibility to erythromycin, clindamycin, penicillin G, and cefaclor by the Etest method (AB-Biodisk, Solna, Sweden) and for susceptibility to tetracycline by the agar diffusion method. The results were interpreted according to the Clinical Laboratory Standards Institute guidelines (15). Erythromycin-resistant strains were differentiated into resistance phenotypes by the double-disk method (20) and screened for the presence of mefA, ermB, ermTR, and prtF1 genes as previously described (2, 9, 16). Pulsed-field gel electrophoresis (PFGE) was performed on the DNA of macrolide-resistant strains after digestion with the enzymes SmaI and SfiI (New England Biolabs, Frankfurt, Germany). Clonal relatedness was defined as a similarity coefficient higher than 80%. For statistical analysis, the chi-square test and the Mantel-Haenszel test for linear trends were applied.All GAS isolates were susceptible to penicillin and cefaclor. The overall rate of resistance to erythromycin was 13.6% (41/ 301 isolates). A trend toward reduced erythromycin resistance over time in this area of Germany was observed (MantelHaenszel test; P ϭ 0.028). The distribution of resistance rates over the study period is shown in Fig. 1. For tetracycline, an...