Clinical Pharmacology of the Fluoroquinolones: Studies in Human Dynamic/Kinetic Models

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Abstract
Traditional antibiotic dosage adjustments, compensate only for disease-induced changes in the serum concentration profile. Dosage adjustments tend to be effective when a well-defined range of concentration is associated with efficacy. However, the bacterial target of antibiotic action-minimum inhibitory concentration (MIC) is variable, because even susceptible bacteria may differ greatly in their antibiotic susceptibility. Newly developed computerized methods for the quantitation of susceptibility allow for testing of integrated kinetic-susceptibility models in patients. Our attention has focused on fluoroquinolones, since they are relatively nontoxic and provide the necessary dosage range needed to elucidate correlations between concentration and response. Studies of patients with nosocomial gram-negative pneumonia reveal that the best correlation parameters of favorable outcome are ∼80% of time over MIC and 24-h area under the time-concentration curve (AUC)—to-MIC values >125.