Objectives:

The increasing prevalence of resistance among S. pyogenes to macrolide antibacterials is a cause for concern, particularly as macrolides are considered the main treatment alternative for penicillin-intolerant patients with tonsillitis/pharyngitis caused by S. pyogenes. Data from the PROTEKT study – a global, longitudinal study to assess the antimicrobial susceptibility of common bacterial pathogens associated with community-acquired respiratory tract infections (RTIs) – have been analysed to assess the prevalence of macrolide resistance among clinical isolates of S. pyogenes collected over 3 years and to assess the activity of the ketolide antibacterial telithromycin (TEL) against such isolates.

Methods:

The MICs of clinical isolates of S. pyogenes collected worldwide as part of the PROTEKT programme over three consecutive respiratory seasons (1999–2002) were determined centrally by NCCLS broth microdilution methods. Isolates were tested for the presence of macrolide resistance genes erm(B), mef(A) and erm(A) subclass erm(TR) using PCR.

Results:

A total of 5034 isolates of S. pyogenes were collected between 1999 and 2002 from 34 countries. Over the 3 years, the prevalence of resistance to erythromycin (MIC >=1 mg/L) was 12.1% (10.4, 9.8 and 14.9% in years 1, 2 and 3, respectively). Rates of resistance varied considerably between countries, ranging from 0% (Ecuador and The Netherlands) to 90.9% (40/44) in China [data from years 1 and 3 (one centre only)]. Of the 622 isolates analysed by PCR, 48.9% (304) tested positive for the mef(A) gene, 23.8% (148) were positive for erm(B), 26.2% (163) were positive for erm(A) subclass erm(TR) and 1.1% (7) were negative for the mechanisms tested. TEL retained potent in vitro activity against S. pyogenes, with 97.5% (4907/5034) of isolates susceptible at concentrations <=0.5 mg/L. Over the 3 years, no major changes in susceptibility to TEL were observed: TEL mode MIC against S. pyogenes was 0.015 mg/L for all 3 years, with an MIC90 of 0.03 mg/L in year 1, 0.015 mg/L in year 2 and 0.25 mg/L in year 3.

Conclusion:

Approximately 12% of S. pyogenes isolates collected worldwide were resistant to macrolides, with mef(A)-mediated resistance the most prevalent mechanism. In contrast, TEL displayed high activity against S. pyogenes (>97% of isolates susceptible), including strains resistant to erythromycin.