Antibiotic pharmacokinetic and pharmacodynamic parameters in pediatric clinical practice.

Progress in the knowledge of antibiotic mechanisms of action allows to determine the pharmacodynamics/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the bacterial species implicated, the location of the infection, and the severity of the disease, these parameters may vary. The PK/PD parameters described in this paper, focus only on blood compartments. These PK/PD parameters best predict efficacy in the most frequent infections (e.g., respiratory, bacteremia, skin and soft tissue infections and intra-abdominal infections). Furthermore, they contribute to the determination of doses and number of administrations per day as well as the determination of minimum inhibitory concentration (MIC) breakpoints. The time above the MIC (T> MIC) is the main criterion for β-lactams: free drug serum levels of these drugs should be above the MIC for at least 40%-50% of the dosing interval to produce adequate clinical and microbiological efficacy. Peak/MIC ratio is the major determinant of the activity of aminoglycosides: in general, peak/MIC ratios should exceed 8-10. Area under the MIC curve (AUC/MIC) is considered for quinolones, macrolides, and vancomycin as the best predictor of efficacy.