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Institut für Medizinische Mikrobiologie und Krankenhaushygiene
Institut für Medizinische Mikrobiologie und Krankenhaushygiene
Universitätsklinikum Frankfurt
Paul-Ehrlich-Straße 40
Haus 40
60596 Frankfurt am Main
Prof. Dr. med. Volkhard A. J. Kempf
Frau M. McGarry
T +49 69 63 01 - 5019
F +49 69 63 01 - 83431
manuela.mcgarry@unimedizin-ffm.de
Prof. Dr. Dr. Thomas A. Wichelhaus
Infectious diseases are of central medical importance despite promising innovations in the field of diagnostics and therapy. The COVID-19 pandemic has demonstrated that infectious agents can pose a substantial threat not only to health, but also to social cohesion, the economy and freedom. Infectious agents also know how to successfully evade antiinfectives by establishing resistance mechanisms. Antibiotics are among the most important medical achievements and are indispensable in modern medicine. They are used to treat bacterial infections in human and veterinary medicine. However, more and more pathogens are becoming resistant to the active substances.
Learn more about the causes and relevance of antibiotic resistance and strategies to counteract the development of resistance.
Antibiotics - the sword in the fight against infectious agents is becoming blunt.
(Lecture at the Health Forum of the University Hospital Frankfurt)
Colonisation/infection with multidrug-resistant bacteria (MDRB) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), cefixime- and azithromycin-resistant Neisseria gonorrhoeae, extended-spectrum beta-lactamase (ESBL)- producing Enterobacterales, carbapenemase-producing Gram-negative pathogens and, last but not least, multidrug-resistant mycobacteria is a growing problem worldwide. Our research focuses on molecular mechanisms of resistance and epidemiology of MDRB.
The alarming increase of antibiotic-resistant bacterial pathogens points to the need for new antiinfective therapies. Consequently, antibiotic resistance has been called one of the world’s most pressing public health problems. A worrisome trend is the spread of carbapenemases (e.g. metallo-β-lactamases) among Gram-negative pathogens that can confer resistance to almost all β-lactams including carbapenems and consequently present a major challenge for treatment of individual patients.
Our research focuses on the development and evaluation of new antimicrobials active against MDRB.
In particular, our research aims at developing a new anti-infective agent by identifying metallo-β-lactamase inhibitors which will restore the bactericidal activity of common β-lactam antibiotics against multidrug-resistant Gram-negative pathogens.
Furthermore, our aim is to develop a much-needed new strategy for the treatment of MDRBs. To this end, we have designed a ‘nitroxoline shuttle’. Nitroxoline is an antibiotic drug that effectively kills a broad variety of bacteria; however, its use is limited to bladder infections due to its inability of reaching other parts of the human body. The ‘shuttle’ is a chemical substance that, when linked to nitroxoline, will allow to safely transport this powerful antibiotic to bacteria in various parts of the human body. In the project, we will manufacture the ‘nitroxoline shuttle’ and carry out tests to characterise its ability to kill bacteria in a targeted manner. This project “Targeted Nitroxoline Delivery for Treatment of Multidrug-resistant Pathogens” (TANDEM) is supported by BMBF under the framework of the JPIAMR – Joint Programming Initiative on Antimicrobial Resistance.
Targeted Nitroxoline Delivery for Treatment of Multidrug-resistant Pathogens
We observed that hematopoietic stem cell transplantation (HSCT) patients colonized by multidrug-resistant bacteria (MDRB) had a higher death rate due to infections in the immediate posttransplant period compared to non-colonized patients.
Our research therefore focuses on the interplay between the immune system and the microbiome. This will allow us to understand if changes in the microbiome are associated with alterations in the cellular immune system. Metabolomic studies will enable us to find potential biomarkers that correlate with a poor microbiome and an altered cellular immune recovery. The obtained data of the microbiome, lymphocyte subpopulations and metabolomics will finally be crossed with clinical data, the colonization status with multidrug-resistant bacteria and outcome data to contribute to the elucidation of higher death rates observed in MDRB-colonized patients with predictive biomarkers.
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