8% (61) Ku-0059436 in vitro resistance to tetracycline, and 0.3% (3) resistance to rifampin. Macrolide resistance phenotypes and genotypes Two hundred ninety five (32.8%) erythromycin resistant isolates were detected among the 898 GAS isolates gathered over the Fedratinib 13-year collection period. The M phenotype was clearly predominant (227 isolates, 76.9%), followed

by the cMLSB (60 isolates, 20.3%) and iMLSB phenotypes (8 isolates, 2.7%) (Table 1). The isolates with the cMLSB phenotype showed high-level resistance to erythromycin and clindamycin (MIC90 ≥256 mg/L), whereas those with the iMLSB and M phenotypes showed lower erythromycin resistance values and susceptibility to clindamycin (Table 1). To highlight, the cMLSB phenotype was more predominant among invasive that in check details non-invasive, 43.8 and 12.6%, respectively. Table 1 Distribution of phenotypes and genotypes among macrolide-resistant S. pyogenes isolates Phenotype No. isolates (%) Invasive/non-invasive Antimicrobial agent(mg/L) Macrolide resistance genotype       Range MIC50 MIC90 erm (B) erm (A) mef (A) msr (D) None gene M 227 (76.9) Erythromycin 1- ≥ 256 32 128 50 87 224 221 1 38 / 189 Clindamycin 0.06-0.5 0.25 0.5 cMLSB 60 (20.3) Erythromycin 8- ≥ 256 ≥256 ≥256 57 11 36 17 2 32 / 28 Clindamycin

1- ≥ 256 ≥256 ≥256 iMLSB 8 (2.7) Erythromycin 2- ≥ 256 16 32 3 8 4 3 0 3 / 5 Clindamycin 0.06-0.5 0.25 0.5 Total 295 (100) Erythromycin 1- ≥ 256 64 256 110 106 264 241 3 73 /222 Clindamycin 0.06-0.5 0.25 256           In the present work, the mef(A) (89.5%) and msr(D) (81.7%)

genes were the most prevalent macrolide resistance determinants. erm(B) and erm(A) were observed in just 37.3% and 35.9% of isolates C1GALT1 respectively (Table 1). Fourteen macrolide resistance genotypes were identified among the 295 erythromycin-resistant isolates (Table 2), with msr(D)/mef(A) (38%) and msr(D)/mef(A)/erm(A)(19.7%) the two most common combination. Both genotypes were associated with the M phenotype. Table 2 Macrolide resistance genotypes of 295 isolates of erythromycin-resistant S. pyogenes , indicating the phenotypes and emm /T types detected Macrolide resistance genotype No. of isolates Phenotypea emm/T typesa (%) cMLSB iMLSB M erm(B) 14 (4.7) 14 – - emm6T6 (1b), emm11T11 (5b) emm28T28 (6c), emm71TNT (1) emm78T11 (1) erm(B)/erm(A) 1 (0.3) 1 – - emm12T12 erm(B)/ msr(D) 5 (1.7) 5 – - emm11T11 (1b), emm28T28 (3) emm88T28 (1) erm(B)/mef(A) 21 (7.1) 20 – 1 emm4T4 (1), emm28T28 (18) emm28TNT(1), emm75T25 (1) erm(B)/ msr(D)/mef(A) 33 (11.2) 8 – 25 emm1T1 (1), emm2T2 (1) emm4T4 (14), emm6T6 (2) emm11T11 (2b), emm12T12 (4) emm28T28 (4), emm75T25 (4) emm84T25 (1) erm(B)/ msr(D)/ erm(A) 2 (0.7) 2 – - emm11T11 (2b) erm(B)/ erm(A)/mef(A) 7 (2.4) 5 2 – emm11T11 (1b), emm28T28 (4) emm77T28 (1b), emm83TNT (1b) erm(B)/ msr(D)/mef(A)/ erm(A) 27 (9.2) 2 1 24 emm1T1 (1), emm4T4 (3) emm11T11 (1), emm12T12 (3) emm75T25 (14),emm81TB3264(1) emm84T25 (4) erm(A)/mef(A) 6 (2.