New pharmacodynamic parameters for antimicrobial agents

The application of pharmacodynamic theories to antimicrobial chemotherapy has greatly improved the prediction of the time course of activity expressed by antibiotics. Being a major component of the antibiotic-bacterium interaction system, pharmacodynamics, when properly integrated with the pharmacokinetics established for the antibiotic, allow better evaluation of the dosage regimen in conjunction with its clinical response. Before this approach becomes effective, detailed background information on the complex antibiotic-bacterium interactions have to be secured. To achieve this, proper characterization of a time-kill curve is a prerequisite. The use of susceptibility endpoints such as the MIC with respect to the antibiotic concentrations achievable in vivo represent the conventional approach to clinical dosing of antimicrobial agents, i.e. by maintaining concentrations above the MIC. Recently, a number of surrogate markers have been proposed by combining suitable pharmacokinetic parameters and susceptibility data, e.g. peak/MIC ratio, AUC>MIC, time above MIC, AUIC etc. to enhance the prediction of clinical outcomes. Attempts have been made to apply these pharmacokinetic/pharmacodynamic markers to antibiotics of the same class as well as to antibiotics from different classes. This review aims to discuss the various microbial dynamic responses in relation to antibiotic exposure and the development of different pharmacokinetic/pharmacodynamic markers for use in current antimicrobial chemotherapy.