Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections

Abstract

The pharmacodynamic principles that link the concentrations of antibiotics within body systems and their effects have been elucidated only recently. Animal work, now confirmed by clinical studies, has shown that for beta-lactam antibiotics, the time that the serum concentration exceeds the minimum inhibitory concentration (MIC) value of the pathogen is a key parameter in predicting a successful clinical and bacteriological outcome. The situation with the macrolides is less clear; time above MIC is the dynamic variable likely to be most closely linked to efficacy for erythromycin and clarithromycin but for azithromycin it appears to be the area under the plasma concentration-time curve: MIC ratio. Different antibiotics are appropriate for the key pathogens in community-acquired respiratory tract infections. For Streptococcus pneumoniae, amoxycillin/clavulanate is effective with varying dosage regimens providing around 40% time above the MIC90, in contrast to the oral cephalosporins and the macrolides for which serum concentrations do not exceed the MIC90. For Haemophilus influenzae, amoxycillin/clavulanate and cefixime are suitable antibiotics whereas macrolides have limited activity. With the exception of amoxycillin, all the beta-lactam and macrolide antibiotics reviewed here perform better against Moraxella catarrhalis than against the other two principal community-acquired respiratory tract pathogens and there is a wide choice of appropriate agents. Knowledge of the pharmacodynamically-linked variables for different antibiotics allows optimization of dosage regimens and direct comparisons across agents for the same variables.