Rational basis for optimizing antibiotic dosing regimens

Adjustment of the antibiotic dosage is usually done taking into account pharmacokinetic parameters. However, as the bacterial response to the antimicrobial effect varies it is important to correlate pharmacokinetics with antimicrobial susceptibility data, the latter measured by determining the Minimum Inhibitory Concentration (MIC). It is now widely accepted that the ratio between the maximum antibiotic concentration achieved in serum and the MIC of the pathogen correlates with efficacy of aminoglycosides and fluoroquinolones. The ratio between the area under the serum concentration-time curve and the MIC correlates with efficacy of aminoglycosides and fluoroquinolones but also of vancomycin, tetracyclines, azithromycin, and quinupristin/dalfopristin. Finally the time for which antibiotic concentration in serum remains above the MIC correlates with efficacy of beta-lactams, most macrolides, and clindamycin. All the above mentioned pharmacodynamic parameters should be considered for optimizing antibiotic dosage.