title: Comparative in vitro activity of telithromycin against macrolide-resistant and -susceptible Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.
abstract: OBJECTIVE
  The first objective was to investigate the in vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents. The second objective was to identify the influence of the erm(B) and mef(A) genes on the susceptibility of Streptococcus pneumoniae to telithromycin.
  
  
  METHODS
  The in vitro activity of telithromycin against S. pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, isolated from the UK and 40 macrolide-resistant S. pneumoniae from four different countries was compared with a variety of antimicrobial agents. The 140 isolates were examined for the presence of the erm(B) and mef(A) genes. The impact of 5% CO(2) on susceptibility testing was also investigated.
  
  
  RESULTS
  Telithromycin showed greatest activity against S. pneumoniae, but also had good activity against M. catarrhalis and H. influenzae, which was independent of their resistance profiles to other antibiotics. The MIC(90) of telithromycin for S. pneumoniae was 0.12 mg/L, which was 64-fold lower than the lowest macrolide MIC; 21% of the S. pneumoniae were macrolide resistant. Thirty-eight per cent of the macrolide-resistant strains were erm(B)-positive and 62% were mef(A)-positive, but no strain contained both genes. The activity of telithromycin was similar to that of azithromycin against both M. catarrhalis and H. influenzae, Erythromycin was slightly less active: 1% and 8% of M. catarrhalis and H. influenzae, respectively, were resistant to erythromycin, but none were resistant to telithromycin. Five per cent of the S. pneumoniae strains and 4% of the H. influenzae strains changed from telithromycin susceptible to non-susceptible entirely because of the incubation conditions. The MIC(50)s and MIC(90)s of S. pneumoniae, M. catarrhalis and H. influenzae increased by one dilution when incubated in CO(2).
  
  
  CONCLUSIONS
  Telithromycin has shown high in vitro activity against S. pneumoniae, including those strains that are macrolide susceptible and resistant as well as M. catarrhalis and H. influenzae. This study has also demonstrated that there is no cross-resistance between erythromycin and telithromycin. The impact of 5% CO(2) on susceptibility testing should be investigated further before providing definite guidelines on telithromycin susceptibility testing.
authors.affiliation: Department of Medical Microbiology, Medical School, University of Edinburgh, Edinburgh EH8 9AG, UK. fwalsh@staffmail.ed.ac.uk
authors.forename: Fiona
authors.initials: F
authors.lastname: Walsh
authors.forename: Francis
authors.initials: F
authors.lastname: Carnegy
authors.forename: Joanne
authors.initials: J
authors.lastname: Willcock
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amyes
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000382:microbiology; D002245:Carbon Dioxide / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D048628:Ketolides; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D002245:Carbon Dioxide; C106791:telithromycin