Resistance determinants and clonal diversity in group A streptococci collected during a period of increasing macrolide resistance

Abstract

Susceptibility to macrolides and lincosamides was investigated with 299 consecutive nonduplicate Streptococcus pyogenes clinical isolates collected over a 6-year period (1992 to 1997) from an area of central Italy. During this period, macrolide resistance rates steadily increased (from 9% in 1992 to 53% in 1997; P < 0.001). The increase was caused by isolates with a macrolide-lincosamide-streptogramin B resistance phenotype, carrying mostly erm(B) but also erm(TR) genes, that were not detected in the first 2 years and were detected with increasing prevalence (8, 5, 26, and 37%, respectively) during the following 4 years. During the same period, the prevalence of isolates with a macrolide resistance phenotype, carrying mef(A) determinants, did not vary significantly; on average it was 13%, with modest rate fluctuations in different years and no definite trend. Molecular typing revealed a remarkable clonal diversity among susceptible and resistant isolates and a notable heterogeneity of the genetic environment of the resistance genes. The analysis of clonal diversity in relation with resistance phenotypes and genotypes revealed that increased macrolide resistance rates were due to a complex interplay of different mechanisms, with a relevant contribution played by an "epidemic" spread of genetic elements carrying the erm(B) gene among the circulating streptococcal population.

FIG. 1.

Prevalence of macrolide resistance phenotypes and genotypes observed during the study period in the 299 S. pyogenes isolates. S, susceptible phenotype (░⃞); M, M resistance phenotype (▪); MLS-erm(B), MLS resistance phenotype with an erm(B) gene (▨); MLS-erm(TR), MLS resistance phenotype with an erm(TR) gene (▧). The number above each column represents the total number of isolates in the indicated year. The prevalence differences observed during the study period were not significant for the M-type resistant isolates and were statistically significant (P < 0.001) for the MLS-type resistant isolates.