Focus of research
In the treatment of bacterial infections, the emergence of resistances is an increasing problem. This results in a more challenging antibacterial therapy and causes numerous cases of death worldwide. Bacterial resistance emerges in terms of different mechanisms and bacteria are adapting to new conditions consistently. Hence using antibiotics leads to an increasing selection of strains with reduced susceptibility.
Developing new antibiotics is one strategy that cannot tackle these challenges alone. In addition to measures of prevention, optimised diagnostics, an evidence-based and rational use of drugs, administration of drug combinations are promising alternatives to preserve their efficacy and deal with bacterial resistances. Combinations of different antibiotics are already used for the treatment of various infectious diseases, e.g. tuberculosis.
The objective of my PhD thesis in the context of the EU project ABIMMUNE of the “Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)” is to develop a non-traditional combination therapy for treatment of respiratory tract infections to minimise emergence of resistance and treatment failures. Particularly bacteria causing respiratory tract infections have a high risk for emerging resistances and are the most frequent causative pathogens for fatal infections.
Combinations of immunomodulatory drugs and disused and neglected antibiotics provide a novel approach to treat these infections. Stimulating the immune system can help to support the antibiotic drug and the human body to overcome an infection.
In the ABIMMUNE project, the influence of these combinations against pathogenic bacteria is investigated. In in vitro investigations for single drugs and combinations minimal inhibitory concentrations (MIC) are determined and time-kill behaviour is assessed. Simulations are performed with the obtained pharmacokinetic (PK) data as concentration-time profiles and pharmacodynamic (PD) data as resulting bacteria concentrations to characterise interactions and effects of the combinations. By linking these results to other human PK data, dosing strategies of synergistic drug combinations will be developed and analysed in animal models by partners of the project.
Finally, differences between in vitro and in vivo will be analysed using the obtained data, the animal models will be optimised and finally simulations for clinical studies will be performed to assess the efficacy of the therapy in a clinical setting.