[Blood and respiratory diffusion of antibiotics. A critical analysis of predictive parameters for clinical...

The implementation of a treatment for lower respiratory tract infections must integrate a pharmacokinetic/pharmacodynamic (PK-PD) approach of antibiotic dosing. The activity of beta-lactam antibiotics is best predicted by the duration of time during which serum concentrations exceed the MIC (T>MIC). T>MIC of 30-40% is sufficient to achieve clinical cure in immunocompetent patients. This threshold is achieved with amoxicillin for penicillin susceptible or resistant Sreptococcus pneumoniae and with amoxicillin-clavulanate and ceftriaxone for S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. For macrolides, the activity is best predicted by T>MIC and for azithromycin and telithromycin by area-under-the-curve/MIC (AUC/MIC). Sufficient PK-PD values are only achieved for macrolides against susceptible strains of S. pneumoniae and against M. catarrhalis; for telithromycin, an AUC/MIC>25, which is necessary for bacterial eradication, is achieved in>99% of patients for S. pneumoniae and M. catarrhalis and>90% of patients for H. influenzae. For fluoroquinolones, both peak/MIC and AUC/MIC are predictors of clinical and bacteriological efficacy. AUC/MIC required ratios vary according to pathogens and severity of diseases from 48 to 125. These thresholds are reached for respiratory pathogens; for S. pneumoniae, AUC/MIC90 ratios of levofloxacin and moxifloxacin are 96 and 192, respectively; the presence of a mutation in parC increases the risk for the acquisition of additional mutations and failure.