Pharmacodynamic and pharmacokinetic considerations in antimicrobial selection: focus on telithromycin.

The effectiveness of empirical treatment for respiratory tract infections (RTIs) with commonly available antimicrobials is threatened by the development of microbial resistance and cross-resistance between treatments. Pharmacokinetic and pharmacodynamic profiling of antimicrobial agents is increasingly being used to select the most appropriate treatment and dosage schedules for RTIs. In addition to enhancing management strategies with existing treatments, these profiles have played a key part in identifying dosage schedules for a new family of semisynthetic antimicrobials, the ketolides. The first member of this family, telithromycin, has potent activity against both common and atypical pathogens involved in RTIs and does not induce resistance to the macrolide-lincosamide-streptogramin B (MLS(B)) antimicrobials in vitro. Its pharmacokinetic profile reveals that telithromycin can be administered once daily without regard for meals, requires no dose reduction in elderly patients or those with hepatic impairment, and penetrates rapidly into respiratory tissues and fluids, a feature probably related to its ability to concentrate inside white blood cells. Pharmacodynamic studies indicate that the area under the concentration-time curve (AUC):minimum inhibitory concentration (MIC) and the peak plasma concentration (Cmax):MIC ratios are important determinants of bacteriological outcome with telithromycin. Telithromycin has a high AUC:MIC ratio compared with macrolide antimicrobials, which is expected to result in enhanced antimicrobial activity. These properties of telithromycin, combined with its good tolerability and low propensity for drug interactions, provide the basis for potent and reliable treatment of RTIs with a convenient, once-daily regimen.