Increasing telithromycin resistance among Streptococcus pyogenes in Europe

Objectives: To assess changes in macrolide and ketolide resistance among Streptococcus pyogenes in Europe and to examine the relationship of resistance to antimicrobial usage. Methods: Clinical S. pyogenes isolates were collected from Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, UK, Croatia, Hungary, Poland, Slovak Republic and Slovenia during 2002-03 (n = 2165) and 2004-05 (n = 2333). Resistance to telithromycin (MIC >2) and erythromycin (MIC ≥ 0.5) was determined by CLSI broth microdilution. Changes in resistance over time and the relationship of resistance to antimicrobial use (European Surveillance of Antimicrobial Consumption data) were assessed. Telithromycin-resistant isolates were characterized by PFGE to determine genetic relatedness and by PCR to detect mefA), erm(A) and erm(B). Results: The erythromycin resistance rate during 2004-05 (11.6%) was similar to 2002-03 (10.4%). The proportion of macrolide-resistant isolates with the constitutive MLS B phenotype increased from 29.3% (2002-03) to 45.7% (2004-05). Telithromycin resistance increased from 1.8% in 2002-03 to 5.2% in 2004-05. For Western Europe, associations of telithromycin and erythromycin resistance, respectively, were found with azithromycin use (R 2 = 0.52 and 0.60), clarithromycin use (R 2 = 0.76 and 0.85) and total macrolide/lincosamide use (R 2 = 0.75 and 0.69). For Eastern Europe, associations of antimicrobial use with resistance were not apparent. The 162 telithromycin-resistant isolates comprised 42 PFGE patterns with 68.5% in eight major PFGE groups. The erm(B) gene was detected in 155 of the 162 telithromycin-resistant isolates. Conclusions: Significant increases in telithromycin resistance occurred from 2002-03 to 2004-05 in Europe. Macrolide use appears to be a factor in the emergence of ketolide resistance among S. pyogenes in Western Europe.