Optimizing therapy with antibacterial agents: use of pharmacokinetic-pharmacodynamic principles in pediatrics

The appropriate dosage of antibacterial agents is essential in achieving both clinical and microbiologic success in the treatment of infections in children. By using in vitro experimental data and animal model outcome data, the pharmacokinetic-pharmacodynamic (PK-PD) parameters predictive of antibacterial effect have been elucidated. For time-dependent drugs such as beta-lactams, the PK-PD parameter of interest is the percentage of time in a dosage interval for which drug concentrations remain above the minimum inhibitory concentration (MIC) of the infecting organism. For concentration-dependent drugs such as aminoglycosides, the PK-PD parameter of interest is the ratio of the area under the plasma concentration-time curve to the MIC. Recent studies using data on clinical and microbiologic outcomes from infected adults and children, combined with data on drug exposure, have confirmed the importance of these parameters and provided estimates of the PK-PD goals of therapy for various antibacterial agents. Application of these PK-PD principles allows rational dosage regimen selection, both for serious infections in critically ill children and for non-life-threatening community-acquired infections.