The Use of In-Vitro Kinetic Models in the Evaluation of β-Lactam/β-Lactamase Inhibitor Combinations

Abstract

In conventional in vitro tests, bacteria are exposed to a constant concentration of antibiotic throughout the period of the test, and in the case of β-lactam/β-lactamase inhibitor combinations the concentrations of each component will be fixed. This does not reflect the situation in man, where the concentrations of antibiotic and inhibitor in the serum and tissues will be constantly changing according to absorption and elimination rates and any metabolism of the compounds. In vitro kinetic models can be used to simulate the concentrations of antibiotics measured in the serum and extravascular fluid of man following conventional dosage and to assess their antibacterial activities. In these studies, in vitro kinetic models have been used in various ways to assess the bactericidal activities of β-lactam/β-lactamase inhibitor combinations. Straightforward comparative studies can be carried out using different antibiotics; comparisons between different β-lactams and β-lactamase inhibitors; studies to look at concentrations of inhibitor required for different pathogens; and, interaction studies to look for synergy or antagonism can be carried out using these models. Examples of all these types of experiment are described below.