title: Pharmacodynamics of an 800-mg dose of telithromycin in patients with community-acquired pneumonia caused by extracellular pathogens.
abstract: The pharmacodynamics of telithromycin, a new ketolide antibacterial, was examined in 115 patients with community-acquired pneumonia (CAP). Patients received telithromycin 800 mg qd for 7-10 days. Pharmacokinetic parameters were determined, and exposure was linked to microbiological outcome using logistic regression analysis. A breakpoint for increased probability of microbiological eradication was developed and was found to be the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) of 3.375. The final logistic regression model of microbiological outcome included body weight and AUC/MIC ratio breakpoint. This model was found in analyses of the entire population and when Streptococcus pneumoniae and Haemophilus influenzae were examined separately. The AUC/MIC ratio target attainment rate is expected to be >99.9% for S. pneumoniae and Moraxella catarrhalis and 93.1% for H. influenzae. This study demonstrated a relationship between telithromycin drug exposure and microbiological outcome. Telithromycin is expected to achieve the drug exposure breakpoint for the majority of isolates causing CAP.
authors.affiliation: Albany College of Pharmacy, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.forename: Sandra
authors.initials: S
authors.lastname: Preston
authors.forename: Vijay
authors.initials: V
authors.lastname: Bhargava
authors.forename: Andre
authors.initials: A
authors.lastname: Bryskier
authors.forename: Roomi
authors.initials: R
authors.lastname: Nusrat
authors.forename: Sonny
authors.initials: S
authors.lastname: Chapel
authors.forename: Manichan
authors.initials: M
authors.lastname: Rangaraju
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D048628:Ketolides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin