Focus of research
[Forschungslinie 1]: Bioanalytics & Microdialysis and Cellculture
The discovery of penicillin by Fleming in 1928 led to the development of antibiotics and represents one of the remarkable achievements in the field of pharmaceutics. Antibiotics allow a potent treatment in the fight against severe infectious diseases such as endocarditis or pneumonia. As a result of their administration, it was possible that, according to the German Federal Statistical Office, the bacterial infections as cause of death in 2012 were far behind cancer and cardiovascular disease. Due to rare new approval of antibiotics and especially the increase in the resistance of bacteria responsible usage of existing antibiotics is becoming increasingly important. Therefore optimised dosing guidelines in the form of patient subgroup-adapted dosage regimens represent a time- and cost-saving method for the use of anti-infectives. In our Dept., the establishment of dosing regimens is based on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships.
The basis of the PK/PD models primarily is either the minimum inhibitory concentration (MIC) as a PK/PD parameter, or the generation of time-kill curves and PK/PD parameters derived from them. The MIC and time-kill curves are determined in vitro in the laboratory. The determination is performed experimentally by in vitro infection models. This determination requires the quantification of bacteria, which is the most time-consuming step in the determination of the respective PK/PD parameter.
My project deals with in vitro determination of MIC and time-kill curves. The determination is performed experimentally with in vitro infection models, which enable a systematic investigation of antibiotic PD for infections caused by bacteria. Taking PK data (drug concentration-time profiles) obtained in clinical trials into account, various scenarios can be mimicked experimentally in vitro, and thereby with the help of PK/PD models recommendations for dosage regimens for the therapeutic practice can be derived. In order to optimise the determination of the parameters, a time- and cost-saving method for the quantification of pathophysiological relevant bacterial species such as Escherichia coli should be developed. This method should be established on the basis of international guidelines such as the EMA guideline for 'Bioanalytical method validation' (2012).