Alarming trend of clarithromycin-resistant Streptococcus pyogenes in Japan (1998-2002)

We investigated annual changes in clarithromycin resistance and resistance genes in 579 strains of Streptococcus pyogenes isolated from patients with symptomatic respiratory tract infections who visited primary medical institutions during the 5-year period from 1998 to 2002. The minimum inhibitory concentrations (MICs) of clarithromycin for S. pyogenes were measured using the standard broth microdilution method according to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines, and strains showing MICs of 1 microg/ml or greater were regarded as being resistant to clarithromycin, according to the resistance standard specified by the NCCLS. The rates of S. pyogenes resistance to clarithromycin were 7.3% overall, 5.8% in 1998, 4.9% in 1999, 7.7% in 2000, 6.4% in 2001, and 11.1% in 2002. While the annual rates fluctuated slightly each year, an overall tendency to increase was observed during the 5-year period. Regarding the macrolide-resistance genes in the macrolide-resistant strains, mefA/E (+)/ ermB(-) was the most common genotype detected in these strains, while the ermB (+)/ mefA/E (-) and mef A/E (-)/ ermB (-) genotypes were detected at about the same rate. The MICs of clarithromycin for the ermB (+) strains tended to be higher than those of the mefA/E (+) strains, but some mefA/E (-) / ermB (-) strains also exhibited high MICs of clarithromycin, similar to those of the ermB (+) strains. The above results indicate that the number of clarithromycin-resistant strains of S. pyogenes is gradually increasing and that the resistance is becoming stronger; thus, special attention must be paid to the appearance of macrolide-resistant strains of S. pyogenes.