Pharmacodynamics of fluoroquinolones

Abstract

Fluoroquinolone antimicrobial agents are highly active against aerobic or facultative gram-negative bacilli. The fluoroquinolones have been shown to be very concentration dependent in their rates of killing and also have a postantibiotic effect against most gram-negative pathogens. These properties resemble those of aminoglycosides more than those of the beta-lactam antibiotics. In animal studies, once daily administration of a dose that produced a high peak concentration/minimal inhibitory concentration (MIC) ratio of > 10-20:1 resulted in significantly better survival than did regimens in which the same daily dose was used on a more fractionated schedule. Studies in patients, most often with ciprofloxacin, demonstrated that the area under the concentration-time curve (AUC)/MIC ratio (AUIC) is the most important predictor of both clinical and microbiological cure. These findings, when combined with microbiological and pharmacokinetic data, provide the rationale and tools needed for targeting the dosage of fluoroquinolones to individual patients on the basis of pharmacokinetics and the susceptibilities of the bacterial pathogens.