title: Impact of carbon dioxide on the susceptibility of key respiratory tract pathogens to telithromycin and azithromycin.
abstract: OBJECTIVE
  To determine the quantitative differences in telithromycin and azithromycin MIC values against Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes obtained using two recommended and commonly used methodologies: CLSI reference standard broth microdilution in ambient air and Etest((R)) concentration gradient in CO(2).
  
  
  METHODS
  Four hundred clinical isolates (S. pneumoniae, n = 200; H. influenzae, n = 100; S. pyogenes, n = 100) were evaluated in seven independent laboratories. Telithromycin and azithromycin MICs were determined using CLSI broth microdilution panels incubated in ambient air and Etest strips incubated in CO(2). Standard quality control reference strains-S. pneumoniae ATCC 49619 (n = 10) and H. influenzae ATCC 49247 (n = 10)-were also tested.
  
  
  RESULTS
  Telithromycin and azithromycin Etest MICs in CO(2) were elevated for all organisms when compared with values obtained using broth microdilution in ambient air. Telithromycin geometric mean MIC values increased in CO(2) by 2.05, 1.00 and 1.78 log(2) dilutions for S. pneumoniae, H. influenzae and S. pyogenes, respectively. The corresponding values for azithromycin were 2.54, 1.21 and 3.0 log(2) dilutions, respectively.
  
  
  CONCLUSIONS
  Telithromycin MICs measured using Etest in CO(2) are consistently elevated compared with those generated by CLSI broth microdilution measured in ambient air. These findings indicate that Etest should not be routinely used for the determination of telithromycin MICs against S. pneumoniae, H. influenzae and S. pyogenes, unless appropriate corrective factors are applied before reporting MICs or applying interpretive susceptibilities. Based on results from this study, Etest MIC breakpoints and quality control ranges are proposed.
authors.affiliation: Laboratories International for Microbiology Studies, Inc., Schaumburg, IL 60173-3817, USA. sbouchillon@ihmaninc.com
authors.forename: Sam K
authors.initials: SK
authors.lastname: Bouchillon
authors.forename: Jack L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: Tim M
authors.initials: TM
authors.lastname: Stevens
authors.forename: Brian M
authors.initials: BM
authors.lastname: Johnson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D048628:Ketolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D002245:Carbon Dioxide; D017963:Azithromycin; C106791:telithromycin