The hidden impact of antibacterial resistance in respiratory tract infection. Re-evaluating current antibiotic therapy.

Pharmacokinetic/pharmacodynamic (PK/PD) parameters derived from animal and clinical models of infection are used to predict bacteriological efficacy. Growing evidence from the clinical setting supports the validity of these parameters in guiding antimicrobial therapy. For example, in otitis media and sinusitis, high bacteriological cure rates are obtained when serum concentrations of beta-lactams and macrolides exceed the MIC of the infecting pathogen for at least 40% of the dosing interval. Likewise, the 24-hour AUC/MIC ratio is a good predictor of both bacteriological and clinical efficacy for azithromycin in otitis media and fluoroquinolones in bacterial pneumonia. The value of PK/PD relationships has been recognized by the National Committee for Clinical Laboratory Standards (NCCLS) as another important factor to consider when establishing susceptibility breakpoints. Recent changes to NCCLS breakpoints for oral beta-lactams for Streptococcus pneumoniae reflect this. Also, PK/PD parameters may play a role in predicting the impact of an antibiotic on the development and spread of resistant organisms. In an era of increasing resistance, we should select agents and doses that provide drug concentrations that exceed the magnitude of the PK/PD parameter required both for efficacy and to combat the emergence and spread of bacterial resistance.