Background and objectiveTelithromycin, a ketolide antibacterial, demonstrates concentration-dependent bactericidal activity against the major pathogens causing community-acquired respiratory tract infections. The objective of this study was to explore the relationships between pharmacokinetic/pharmacodynamic predictor variables, such as area under the plasma concentration-time curve (AUC) over minimum inhibitory concentration (MIC) [AUC/MIC], maximum plasma concentration (Cmax) over MIC (Cmax/MIC) and microbiological outcome from telithromycin therapy for community-acquired pneumonia (CAP).Patients and methodsData were pooled from five phase III studies of oral telithromycin (800mg once daily for 7–10 days) for the outpatient treatment of adults with CAP. Only subjects with a single pathogen isolated at baseline, a telithromycin MIC determination and at least one plasma pharmacokinetic sample were included. Bacteriologically modified intent-to-treat (bmITT) and bacteriologically evaluable per protocol (PPb) populations were analysed. Individual AUC and CmaxBayesian estimates were obtained with a population pharmacokinetic model. Logistic regression, nonparametric smoothing, and classification analysis and regression tree (CART) were used to assess the relationship between AUC/MIC and Cmax/MIC and microbiological outcome by pathogen.ResultsThe bmITT population included 224 patients (Streptococcus pneumoniaein 113,Haemophilus influenzaein 89 andStaphylococcus aureusin 22). Median telithromycin MIC was 0.015 µg/mL forS. pneumoniae, 2.0 µg/mL forH. influenzaeand 0.12 µg/mL forS. aureus, with median AUC/MIC of 907.1, 6.9 and 98.4, and median Cmax/MIC of 172.0, 1.3 and 20.4 for the three pathogens, respectively. Both logistic regression and nonparametric smoothing showed the probability of microbiological cure to be consistently greater than 90% over the observed range of predictor variables. No reliable AUC/MIC or Cmax/MIC breakpoints were identified by CART.ConclusionTelithromycin exhibits near-maximal efficacy against three major pathogens causing CAP at a dose of 800mg once daily.