title: Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae.
abstract: OBJECTIVE
  To compare the probability of target attainment (PTA) for macrolides and ketolides against penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae in both serum and epithelial lining fluid (ELF) of patients with community-acquired pneumonia (CAP).
  
  
  METHODS
  Monte Carlo simulations were used to assess the attainment of the bacterial eradication-linked pharmacodynamic index of the free drug area under the concentration-time curve over 24 hours to minimum inhibitory concentration (fAUC(0-24)/MIC90) by azithromycin, clarithromycin, and telithromycin, at therapeutic doses, against penicillin-susceptible, intermediate, and resistant S. pneumoniae.
  
  
  RESULTS
  In serum, azithromycin and clarithromycin were found to have a probability of attaining the recommended fAUC(0-24)/MIC90 ratio of 30 in 50.2% and 74.6%, respectively, of CAP patients with penicillin-intermediate strains, and a probability of 36.9% and 60.7%, respectively, in cases of penicillin-resistant strains. Telithromycin maintained a probability of reaching the fAUC(0-24)/MIC90 ratio of 30 in serum and ELF in 89.1% of CAP patients, regardless of the penicillin resistance of the strain.
  
  
  CONCLUSIONS
  Clarithromycin results in a higher PTA than azithromycin in the treatment of penicillin-susceptible S. pneumoniae, but both of these agents exhibit a decreasing efficacy as S. pneumoniae penicillin resistance increases. When compared to clarithromycin and azithromycin, telithromycin maintains higher PTA in CAP patients with penicillin-resistant strains of S. pneumoniae.
authors.affiliation: College of Pharmacy, University of Minnesota, 1110 Kirby Dr., Duluth, MN 55812, USA. noreddin@umn.edu
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Noreddin
authors.forename: Walid F
authors.initials: WF
authors.lastname: El-Khatib
authors.forename: Jason
authors.initials: J
authors.lastname: Aolie
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Salem
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000097:blood / Q000493:pharmacokinetics; D017291:Clarithromycin / Q000097:blood / Q000493:pharmacokinetics; D017714:Community-Acquired Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D048628:Ketolides / Q000097:blood / Q000493:pharmacokinetics; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D011336:Probability; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin