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 developme nt of microbial resistance and cross-resistance between treatments. Pharmac okinetic and pharmacodynamic profiling of antimicrobial agents is increasin gly being used to select the most appropriate treatment and dosage schedule s for RTIs. In addition to enhancing management strategies with existing tr eatments, these profiles have played a key part in identifying dosage sched ules for a new family of semisynthetic antimicrobials, the ketolides. The f irst member of this family, telithromycin, has potent activity against both common and atypical pathogens involved in RTIs and does not induce resista nce to the macrolide-lincosamide-streptogramin B (MLSB) antimicrobials in v itro. Its pharmacokinetic profile reveals that telithromycin can be adminis tered once daily without regard for meals, requires no dose reduction in el derly patients or those with hepatic impairment, and penetrates rapidly int o 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 c oncentration (MIC) and the peak plasma concentration (C-max):MIC ratios are important determinants of bacteriological outcome with telithromycin. Teli thromycin has a high AUC:MIC ratio compared with macrolide antimicrobials, which is expected to result in enhanced antimicrobial activity. These prope rties of telithromycin, combined with its good tolerability and low propens ity for drug interactions, provide the basis for potent and reliable treatm ent of RTIs with a convenient, once-daily regimen.