[Pharmacokinetic/pharmacodynamic analysis to optimize antibacterial treatments: prediction of efficacy by using...

The aim of this work is to provide a methodology to predict the potential efficacy of standard dosage schedules established for antimicrobials when used in clinical practice and administered to patients with different demographic characteristics. It is based on the application of pharmacokinetic and pharmacodynamic criteria (PK/PD analysis) to optimize dosification of this type of drug. Pharmacokinetic parameters such as the area under the plasma concentration-time curve (AUC) or maximum plasma concentration (Cmax) can be estimated from population kinetic models for each type of patient. Microbiological information, such as the MIC value, is also required. Using the above mentioned information and applying the Montecarlo simulation technique the probability of achieving the recommended value of a substituted variable related to efficacy may be estimated. The proposed methodology has been applied to levofloxacin when reportedly administered to patients showing different characteristics. The results reveal that this method allows us to know a priori whether or not the standard dosage is appropriate for a particular patient for whom the treatment is indicated. In summary, the proposed methodology provides us with a strategy for dosage individualization of antimicrobial agents that can be applied before initiating the treatment with no need for monitoring drug concentration, leading to an increase of clinical efficacy as well as a decreased risk of resistance development.