Pharmacodynamics of Quinolones

Increasing attention has focused on prediction of outcomes by various pharmacodynamic (PD) parameters. These have been extensively reviewed by Wise and colleagues [37,38]. Quinolones exhibit concentration-dependent killing and both the serum peak concentration to inhibitory concentration (Cmax:MIC) ratio and area under the serum inhibition curve (AUIC) can be used to model clinical and bacteriological response in community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECBs). Efficacy cutoff points of Cmax/MIC ratios of 12 and AUIC ratios of 100-125 mg/liter hr predict response and eradication rates of >80%, bacterial eradication within 48 hr (for fluoroquinolones), and development of resistance in <10% of cases. These indices, together with a further PD parameter—intensity of antibiotic effect (IE)—can also be used to predict minimum dosages required to attain their cutoff points. For some of the older quinolones, PD parameters indicate unsatisfactory outcomes or the need to increase dose or dose frequency. The newest agents—moxifloxacin, gatifloxacin, and gemifloxacin—easily exceed cutoff points at current dose levels.

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