Pharmocodynamie des nouvelles fluoroquinolones

Abstract

The pharmacodynamic parameters which permit an accurate prediction of the therapeutic success of fluoroquinolone treatment are the following: the inhibitory quotient (inhibitory quotient, IQ; maximum concentration of the antibiotic (Cmax); minimum inhibitory concentration (MIC) [IQ: Cmax/CMI ratio]) and the area under inhibitory curve(area under inhibitory curve, AUIC; area under curve, AUC [AUIC: AUC 0→ 24h/MIC ratio]). An IQ of over 10 and/or an AUIC between 120 and 250 indicates a success rate of over 85%. The optimization of the AUIC also results in a significant reduction in the time required to render the biological samples negative (an AUIC of over 190 guarantees bacteriological suppression in 90% of cases before the sixth day of treatment). The IQ and AUIC are also pharmacodynamic indicators for the risk of resistant mutant strain selection. This risk is minimal when the IQ is over 10, or when the AUIC is over 100. The weaker the ratio between the concentration likely to prevent in a given bacterium the emergence of resistant mutants (concentration for the prevention of resistance, CPR) and CMI, the less probable is the risk of resistance. The presence of a methoxy group on carbon 8 considerably reduces the CPR. A careful consideration of the pharmacodynamics involved in the prescription of these drugs should allow these new fluoroquinolones to be judiciously used, thereby maintaining their therapeutic efficacy.