We test the efficacy of new and old antibiotics as well as other therapeutics, individually and in combinations, for their spectrum of activity against various human pathogenic bacteria. We also investigate the emergence and mechanisms of resistance to these agents. We are also remotely testing new diagnostics for industry partners on clinical isolates to evaluate specificity and sensitivity as well as detection limits.
Current and recently completed Projects*
* Since contract research is often covered by a confidentiality agreement prior to publication, we cannot present all ongoing projects.
ARTEMIS
Antibiotic Resistance Testing & Evaluation of Materials for In vitro Susceptibility
Project period: 10.2019-12.2020
Pharma-Partner: Shionogi Europe
Before an antibiotic is approved, thousands of clinical isolates need to be assessed for their minimum inhibitory concentration to this agent, from which so-called clinical break points can then be derived, defining the boundary for each antibiotic/species combination between resistant (R) and sensitive (S). Here, the IIMK participated in such a study for Cefiderocol.
AquaSpark
Preoperative testing for the detection of Staphylococcus aureus in clinical patient samples using AquaSparkTM technology
Pharma-Partner: NEMIS Technologies AG
Project period: 03.2020-12.2020
In this project, a luminescence-releasing probe was investigated for its specificity and sensitivity to Staphylococcus aureus as well as the detection limit of the point-of-care test.
CORMs
Carbon monoxide-releasing nonwovens as innovative antibacterial wound dressings
Project partner: Innovent e.V
Project period: 03.2020-08.2021
Carbon monoxide (CO) is a cytotoxin because it disrupts electron transport at the cell membrane, which is the basis for all processes in the cell. Since in bacteria the cell membrane is the only compartment and is almost immediately accessible to CO, CO acts much more rapidly and selectively here compared to human cells, which are composed of numerous specialized intracellular compartments. CO is poorly soluble in aqueous media, but can be trapped in so-called CO-releasing molecules (CORMs) and delivered at a high concentration at the target site by certain physicochemical signals (such as light). In a previous project, we demonstrated in vitro that CORMs woven into a nanofleece of poly-lactate can kill their own bacterial biofilms. This project will demonstrate the efficacy of CORM nanofleeces in vivo, in a mouse model.
The project is funded by the Volkswagen Foundation under grant number 95384.
DePhage
Project partner: Phage Technology Center
Project period: 01.08.2019-31.07.2020
The proliferation of carbapenemase-producing enterobacteria (CPE) limits treatment options, posing a serious threat to healthcare and the public. Of particular concern are metallo-β-lactamases, such as VIM, that are not inhibited by novel β-lactamase inhibitors, such as avibactam or relebactam. In enterobacteria colonize the gut, making decolonization attempts of CPE with antibiotics impossible and leading to disbiosis of the gut flora. Affected 'silent carriers' of CPE are therefore a common cause of clinical outbreaks and promote the spread of CPE in the community.
In contrast to antibiotics, bacteriophages (viruses that infect bacteria)) could provide an alternative strategy against CPE. The major advantage of bacteriophages (also called phages) is that they are very specific to certain bacterial species or even strains and thus could specifically infect and kill certain strains of CPE without damaging the intestinal flora, increasing the likelihood of success of decolonization. Development of resistance to an individual phage strain is negligible from a clinical standpoint because the natural phage reservoir or phage evolution is highly dynamic and follows the evolution of bacteria. Thus, the pool of new phage variants appears to be unlimited. Nevertheless, decolonization by phages theoretically carries the risk of accelerated spread of the corresponding carbapenemase genes by horizontal gene transfer to other strains or species. This risk must be investigated before a clinical trial can be conducted.
In the DePhage study, the risk of gene transfer by therapeutic phages will therefore be assessed.
The project is carried out within the framework of the Center for Sepsis Control and Care (CSCC) and funded by the German Federal Ministry of Education and Research under FKZ 01EO1502.