Intrinsic reduced susceptibility of serotype 6 Streptococcus pyogenes to fluoroquinolone antibiotics

Background. Fluoroquinolone resistance is common in Staphylococcus aureus, is increasing in Streptococcus pneumoniae, and is reported in Streptococcus pyogenes. Methods. We surveyed 384 clinical isolates of S. pyogenes, isolated during 2002-2003, for susceptibility to ciprofloxacin. We performed nucleotide sequencing of the parC and gyrA genes and determined the M/emm type for selected isolates. Additionally, we analyzed M/emm type 6 S. pyogenes isolated during 1918-2003 from diverse locations. Results. Of the survey isolates, 10.9% had reduced zones of inhibition to ciprofloxacin in the disk-diffusion test and had elevated minimum inhibitory concentrations to other fluoroquinolones, compared with those of fully susceptible isolates. Of the resistant isolates, 90.5% were M/emm type 6, and all sequenced M/emm type 6 isolates contained a serine-to-alanine substitution at position 79 in parC. Strikingly, the same findings were also present in macrolide-resistant isolates from a recent outbreak of S. pyogenes infection in Pittsburgh and in the Lancefield reference strain of M type 6, which was isolated in 1918, decades before the development of fluoroquinolone antibiotics. Conclusion. M/emm type 6 S. pyogenes has intrinsic reduced susceptibility to fluoroquinolones, as a result of a polymorphism in parC. This finding was also demonstrated in erythromycin- resistant M/emm type 6 S. pyogenes, which raises concern for the emergence of multidrug-resistant S. pyogenes.