Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens

Pharmacodynamic parameters, such as the rate of bactericidal activity with increasing drug concentrations, post-antibiotic effect, sub-MIC effects, post-antibiotic leukocyte enhancement and first-exposure effect, more accurately describe the time course of antimicrobial activity than the MIC and MBC. Aminoglycosides and quinolones exhibit concentration-dependent killing and induce prolonged post-antibiotic effects. The amount of drug rather than the dosing frequency determines the efficacy of these drugs. However, high peak levels can reduce the emergence of resistance, and once-daily dosing of aminoglycosides can also reduce nephrotoxicity and ototoxicity. On the other hand, beta-lactam antibiotics show time-dependent killing and produce prolonged post-antibiotic effects only with staphylococci. The frequency of drug administration is an important determinant of outcome for these drugs, as the duration of time serum levels exceed the MIC is the major determinant of efficacy.