Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of community-acquired respiratory tract infections

Abstract

To achieve bacteriologic and clinical success, sufficient concentrations of antimicrobial at the site of infection must be maintained for an adequate period of time. These dynamics are determined by combining drug pharmacokinetic and pharmacodynamic (PK/PD) data with minimum inhibitory concentrations. Bacteriologically confirmed failures have been reported in otitis media and, with a lesser degree of evidence, in pneumococcal pneumonia with a variety of agents that include beta-lactams, macrolides and fluoroquinolones. These failures have been shown to be due to infection by resistant pathogens or suboptimal therapy. However, no clinical failure has been reported during therapy for bacteremic pneumococcal pneumonia with adequate doses of beta-lactams. The failures reported with macrolides or fluoroquinolones have been due to either preexisting resistance to these agents that cannot be overcome by increasing the dose of the antimicrobial or, more rarely, the emergence of resistance during therapy. In this review, we offer an overview of the most important attributes of the main antimicrobials that are currently used in the treatment of community-acquired respiratory tract infections from a PK/PD perspective.