Some new concepts in antibacterial drug therapy

Abstract

The goal of antibacterial therapy is to eradicate tissues of infecting organisms. However, achievement of desired outcome will depend on a number of drug-, pathogen- and patient-related factors. Neither microbiological pharmacodynamic activity (as measured by minimum inhibitory concentration [MIC] or minimum bactericidal concentration [MBC] in vitro conditions) nor pharmacokinetic data of drug in the host alone can adequately describe the complex interaction between the antibacterial agent, the invading bacteria and the host, culminating in successful bacterial elimination. Accumulating contemporary data especially in the last one-and-half decades from in vitro studies, animal models of infection and clinical trials have shown that bacterial killing may be described as a function of either drug concentration (concentration-dependent killing; CDK) or time of exposure (time-dependent killing; TDK). Since the duration of exposure is a function of drug disposition in the host and is measured by pharmacokinetic parameters of serum drug concentration (C m a x ), simple correlations can be made to optimize antibacterial chemotherapy. These evidence-based correlations have shown that C m a x and area under the curve (AUC) when integrated with an antibacterial pharmacodynamic parameter of MIC or MBC, the ensuing kineto-dynamic hybrid parameters, like C m a x /MIC or AUC/MIC ratios and the time during which the antibacterial concentration remains above the MIC or MBC (t > MIC or MBC) become important determinants of deciding the dose regimens of an antibacterial agent which shows CDK (e.g. aminoglycosides; fluoroquinolones; metronidazole) orTDK (β-lactam; macrolide; oxazolidinone antibiotics) properties, respectively. The present communication describes how the new concepts of CDK and TDK kinetics when considered and applied along with the property of post-antibiotic effect (PAE), displayed by certain antibiotics can make the antibacterial therapy cost-effective, safe and efficient. PAE not only can mediate an enhanced antibacterial efficacy but also prevent emergence of bacterial resistance.