title: Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003.
abstract: BACKGROUND
  Increased levels of macrolide-resistant Streptococcus pyogenes in focal regions of the United States have been reported. The purpose of this study was to determine the antimicrobial susceptibility of a large collection of S. pyogenes isolates from throughout the United States and to elucidate the mechanisms of resistance and genetic relatedness of macrolide-resistant isolates.
  
  
  METHODS
  During 2002-2003, a total of 1885 S. pyogenes clinical isolates were obtained from 45 US medical centers. Susceptibility to penicillin, cefdinir, erythromycin, azithromycin, clarithromycin, clindamycin, telithromycin, and levofloxacin was determined. Macrolide resistance phenotypes were determined by double-disk diffusion, and macrolide resistance genotypes were determined by polymerase chain reaction and sequencing. All macrolide-resistant isolates and all isolates recovered from sterile sites were further characterized by pulsed-field gel electrophoresis (PFGE) and emm typing.
  
  
  RESULTS
  The majority (85%) of isolates were pharyngeal. Resistance was detected to erythromycin (6.8% of isolates), azithromycin (6.9%), clarithromycin (6.6%), clindamycin (0.5%), telithromycin (0.2%), and levofloxacin (0.05%). The macrolide-resistance phenotype distribution was as follows: macrolide-lincosamide-streptogramin B (MLSB), 56% of isolates (inducible, 47%; constitutive, 9%); and M, 44%. The genotypes detected were as follows: ermA, 46% of isolates (95% with inducible MLSB phenotype); mefA, 43% (all with M phenotype); and ermB, 8.5% (45% with inducible MLSB and 45% with constitutive MLSB). Three isolates with constitutive MLSB phenotypes had 23S ribosomal RNA mutations. The 129 erythromycin-resistant isolates belonged to 28 emm types and 44 PFGE patterns, with 51% of the isolates in 4 major PFGE clones each associated with a predominant emm type (emm75, emm58, emm12, and emm114) and resistance genotype (mefA or ermA)).
  
  
  CONCLUSIONS
  The population of macrolide-resistant S. pyogenes isolates in the United States is small, but it includes several large clones with potential for expansion.
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1009, USA. sandra-richter@uiowa.edu
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Richter
authors.forename: Kristopher P
authors.initials: KP
authors.lastname: Heilmann
authors.forename: Susan E
authors.initials: SE
authors.lastname: Beekmann
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Miller
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Miller
authors.forename: Cassie L
authors.initials: CL
authors.lastname: Rice
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Doern
authors.forename: Sean D
authors.initials: SD
authors.lastname: Reid
authors.forename: Gary V
authors.initials: GV
authors.lastname: Doern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018942:Macrolides / Q000494:pharmacology*; D008875:Middle Aged; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides