Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

Abstract

We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and emm gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. and streptogramin B antibiotics); these isolates were confirmed to be mef(A) and erm(A), respectively. Three unique mef(A) clones and four unique erm(A) clones were identified among the resistant isolates. The MIC at which 50% of isolates are inhibited (MIC 50 ) for the mef(A) strains was 16 g/ml, while the MIC 50 for erm(A) strains was 8 g/ml. The finding of high levels of macrolide resistance among pharyngeal isolates of GAS for a second successive year in our community raises the concern that this problem may be more common in the United States than was previously appreciated. Longitudinal surveillance of isolates from multiple centers is needed to define the prevalence of antimicrobial agent-resistant GAS in the United States.Sore throat is the most common complaint for which older children and adolescents seek acute medical care (9). Group A streptococci (GAS) are the most frequent and important cause of bacterial pharyngitis in children and adults (7). Penicillin V remains the treatment of choice for GAS pharyngitis (2, 8), and macrolides are recommended only for patients who are allergic to penicillin. Nonetheless, azithromycin is increasingly prescribed because its short course of dosing and single daily dosing are attractive to both parents and practitioners.A high prevalence of macrolide resistance among GAS has been recognized in Europe and Japan for many years. However, the rates of macrolide resistance among GAS in the United States have remained low (4,12,16,19,20). In the spring of 2001 we documented the emergence of a high level of macrolide resistance in pharyngeal isolates of GAS in Pittsburgh, Pa., as part of a longitudinal surveillance study of schoolchildren (22). A 38% incidence of macrolide resistance was also found in community isolates of GAS during the same time period. The purpose of this study was to investigate trends in macrolide resistance in pharyngeal GAS over time in our region. MATERIALS AND METHODS GAS isolates. Beginning in September 2001, testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered from the ...

Emergence of Erythromycin- and Clindamycin-Resistant Streptococcus pyogenes emm 90 Strains in Hawaii

“…Further studies need to be done on the 250-kb genomic fragment of our drugresistant isolates to understand whether emm 90.4b developed drug resistance from a genomic insertion. Clonal spread of erythromycin-resistant strains belonging to a single emm type has been reported (14,19,24,26). Our study shows similar concerns of clonal emergence in Hawaii with this multidrugresistant emm type.…”

“…Resistance of Sreptococcus pyogenes to macrolides and lincosamides has been reported, and overenthusiastic use of several macrolides may further increase this problem (14,15,19,27,28). A few emm types, such as emm 4, 6, 12, 58, 75, 77,…”

Rapid Inversion of the Prevalences of Macrolide Resistance Phenotypes Paralleled by a Diversification of T and emm Types among Streptococcus pyogenes in Portugal

“…1). In sharp contrast to the data presented here, the increases in occurrence of strains expressing the M phenotype documented elsewhere were also paralleled by an increase in the overall macrolide resistance rate (8,9,11). Contrary to isolates expressing the MLS B phenotype, those expressing the M phenotype were found among a diverse group of T/emm-type associations and usually at least one-half of the total number of associations found each year was necessary to account for 80% of the isolates.…”

“…1), was not previously described in GAS to the best of our knowledge. This shift could not be attributed simply to the reduction in the number of isolates defined by T12 emm22 and the absence of other T/emm-type associations expressing the MLS B phenotype that could take its place, or by the emergence of a limited number of highly successful strains expressing the M phenotype and specific T/emm-type associations as documented in North America (8,11). Since the data presented do not offer firm clues, we can only speculate as to the reasons behind this shift.…”

Streptococcus pyogenes Isolates with High-Level Macrolide Resistance and Reduced Susceptibility to Telithromycin Associated with 23S rRNA Mutations

“…However, in southwestern Pennsylvania, a sudden increase (3.7 to 35%) found during a two-month period in 2002 has raised concern that macrolide-resistant GAS may be more common than is obvious from overall yearly surveillance data (5). Telithromycin is the first ketolide, a new class of antibacterial agents, and has been reported to be active against macrolide-resistant GAS expressing the efflux gene mef(A) and the inducible methylase gene erm(A) subclass erm(TR) but not active against most isolates expressing the methylase gene erm(B) (3).…”