Pharmacokinetics and pharmacodynamics of oral β-lactam antibiotics as a two-dimensional approach to their efficacy

Abstract

Pharmacokinetic and pharmacodynamic parameters are increasingly recognized as important determinants of the therapeutic efficacy of an antibiotic. For β-lactam antibiotics, the most important determinant of the antimicrobial efficacy, and hence predictor of therapeutic efficacy, is the length of time that serum concentrations exceed the MIC. Dosing schedules for β-lactam antibiotics should maintain serum concentrations above the MIC for the bacterial pathogen for at least 50% of the dosing interval to achieve therapeutic efficacy and prevent the development of resistance. This is a basic criterion for the clinical efficacy of β-lactams. A combination of microbiological activity and pharmacokinetic characteristics was applied to calculate the time that serum antibiotic concentrations exceed the MIC for the major respiratory tract pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Klebsiella pneumoniae. In contrast with some other oral β-lactam antibiotics, cefpodoxime 200 mg bd maintains serum concentrations above the MIC for each organism for at least 50% of the dosing interval and may therefore be an attractive choice for empirical therapy of community-acquired lower respiratory tract infections.