title: Activities of 16-membered ring macrolides and telithromycin against different genotypes of erythromycin-susceptible and erythromycin-resistant Streptococcus pyogenes and Streptococcus pneumoniae.
abstract: OBJECTIVE
  To test four 16-membered macrolides (josamycin, spiramycin, midecamycin and rokitamycin) along with other compounds in the same class (erythromycin, clarithromycin, roxithromycin and azithromycin) plus clindamycin and telithromycin, against Streptococcus pyogenes and Streptococcus pneumoniae isolates with well-characterized resistance genotypes.
  
  
  METHODS
  Four hundred and eighty-six isolates of S. pyogenes and 375 isolates of S. pneumoniae were assayed for their macrolide susceptibilities and investigated by PCR to detect their different erythromycin resistance genes. All strains had been isolated over the period 2002-2003 from specimens of different human origin obtained in 14 different Italian centres.
  
  
  RESULTS
  All 16-membered macrolides showed very low MICs (MIC(50)s and MIC(90)s, < or =0.06-0.5 mg/L) for the erythromycin-susceptible isolates and for those with the M phenotype, but the telithromycin MICs for the M-type isolates were at least four times higher (MIC(90)s, 0.5 mg/L). In S. pyogenes, the MIC(50)s of 16-membered macrolides for the cMLS(B) isolates were > or = 256 mg/L, whereas that for telithromycin was 4 mg/L; the MIC(50)s of 16-membered macrolides and telithromycin ranged from < or = 0.06 to 0.5 mg/L for the iMLS(B) isolates with erm(A) and from 0.12 to > or = 256 mg/L for those with erm(B). In S. pneumoniae, the MIC(50)s of the 16-membered macrolides for the cMLS(B) isolates ranged from 0.5 to 128 mg/L, whereas for the iMLS(B) isolates their values ranged from < or = 0.06 to 4 mg/L; the MIC(50)s and MIC(90)s of telithromycin for both the cMLS(B) and the iMLS(B) isolates ranged from < or = 0.06 to 0.12 mg/L.
  
  
  CONCLUSIONS
  MICs ranged for all the drugs, except telithromycin, from < or = 0.06 to > or = 256 mg/L, with 15% to 30% resistant S. pyogenes for all drugs tested except clindamycin (8%) and telithromycin (5.4%) and 10% to 40% resistant S. pneumoniae for all drugs tested except telithromycin (0.3%). In both S. pyogenes and S. pneumoniae, erythromycin resistance related to a mef gene meant that telithromycin MICs were definitely higher than in erythromycin-susceptible isolates, although telithromycin susceptibility was preserved in all cases. In S. pyogenes, the activity of both 16-membered macrolides and telithromycin against the iMLS(B) strains proved to be dependent on the erm gene involved, being greater against isolates with erm(A).
authors.affiliation: Dipartimento di Patologia, Sezione di Microbiologia, Università degli Studi di Verona, Strada Le Grazie 8, Verona, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Mazzariol
authors.forename: Raffaella
authors.initials: R
authors.lastname: Koncan
authors.forename: Luca Agostino
authors.initials: LA
authors.lastname: Vitali
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cornaglia
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D048628:Ketolides / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000453:epidemiology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; C106791:telithromycin