Tetracycline and macrolide co-resistance in Streptococcus pyogenes: co-selection as a reason for increase in macrolide-resistant S. pyogenes?

In Denmark, tetracycline resistance in Streptococcus pyogenes is frequent (>30%) whereas macrolide resistance is low (<5%). The aim of this study was to investigate the genetic background of tetracycline- and macrolide resistance in macrolide-resistant S. pyogenes (MRSP) and to investigate the correlation between the use of macrolide and tetracycline and macrolide resistance using international data. A total of 133 MRSP isolates were received at Statens Serum Institut from nine Danish clinical microbiology laboratories between. November 2000, and November 2002. The macrolide-resistance genes, erm(B), erm(A), and mef(A) were detected in 46%, 18%, and 32% of the tested MRSP isolates, respectively. In 4% of MRSP isolates, none of the MR genes were detected. Tetracycline resistance was found in 52% of MRSP. Tetracycline resistance was encoded by either tet(M) or tet(O). erm(B) and mef(A) were associated with tet(M). Sixteen different T types were detected among the 133 MRSP. Analysis of the importance of antibiotic use for development of macrolide resistance in S. pyogenes showed no correlation with macrolide use alone (p = 0.15) but a significant correlation (p = 0.03) for the combination of macrolide and tetracycline use. The frequency of macrolide resistance in Danish S. pyogenes was low and mainly due to erm genes. A high frequency of macrolide-tetracycline coresistance in S. pyogenes is found in many countries including Denmark, hence tetracycline use must be considered as a co-factor in selection of MRSP.