Pharmacodynamics of Quinolone Antimicrobial Agents

Pharmacodynamics describes the relationship between measures of drug levels in serum and tissue fluids and the antimicrobial and toxicologic effects of drugs (5, 10, 17, 49). While there have been numerous studies describing the pharmacokinetics of fluoroquinolones in serum and tissues, there has been much less emphasis on describing the time course of antimicrobial activity with these drugs. The MIC and minimal bactericidal concentration have been the major measures of the antimicrobial effect of the quinolones. Although these parameters are useful in defining the potency of the drug against a particular pathogen, they do not provide any information on the time course of antimicrobial activity. Other measures, such as the rate of bacterial killing with increasing concentrations of drug and persistent effects that last after antimicrobial exposure, provide a much better description of the time course of antimicrobial activity. This chapter focuses on the pharmacodynamic characteristics of the quinolone antimicrobials in in vitro models, in animal infection models, and in humans. We hope to demonstrate that there are many more similarities in results among the various models than there are differences.