CD-3: Individualized antibiotic therapy for chronic lung infections

Coordinators: C. Lange (RCB, UzL), K.F. Rabe (GHD, CAU), S. Niemann (RCB, UzL)

The spread of antibiotic-resistant pathogens is increasing worldwide. They are of direct relevance for chronic inflammatory disease, including those associated with lung infections. CD-3 assesses the clinical application of new, individualized treatment strategies against multi-resistant tuberculosis or chronic bronchitis (e.g. COPD) with multi-resistant Pseudomonas infections.

 

What does this research area’s work build on?

Clinical research of lung diseases in Schleswig-Holstein is particularly renowned in the areas of COPD and tuberculosis. The UKSH clinics at our locations in Kiel and Lübeck, the LungenClinic Großhansdorf and the Medical Clinic at the Research Center Borstel, Leibniz Lung Center, have been working together in the field of COPD for many years through the "Airway Research Center North" of the German Centre for Pulmonary Research (DZL). The Research Center Borstel hosts the National Reference Center for Mycobacteria (NRZ), and the most important Mycobacterium is Mycobacterium tuberculosis, the causative agent of tuberculosis. It also hosts the experimental mycobacteriology group and the clinical tuberculosis unit of the German Center for Infection Research (DZIF).

In recent years, the responsible researchers from CD-3 have made important contributions which have changed the diagnostics and treatment of both diseases.

What are the main research objectives?

The researchers aim to develop new treatment concepts for patients with COPD with Pseudomonas aeruginosa colonization, in which the pathogens are often resistant to multiple classes of antibiotics, and for patients with multi-resistant tuberculosis, for which there are currently very limited treatment options.

Patients with advanced COPD and Pseudomonas aeruginosa colonization shall be treated more effectively based on evolutionary principles of the development of antibiotic resistance, and of compensation mechanisms. For patients with multi-resistant tuberculosis, the analysis of entire genomes of the tuberculosis bacteria (genoytpe) is used to make predictions of antibiotic resistance (phenotype), and thus design effective therapy in an individualized form faster. In the case of Pseudomonas infections, predictions of patient-specific evolution of the pathogens is used to develop sustainable treatment through which both the pathogen is eliminated and the spread of resistance is minimized.

What makes this research area special?

The researchers from CD-3 work at the interface between fundamental research and clinical application. After material has been taken for diagnosis of an infection with Pseudomonas aeruginosa or Mycobacterium tuberculosis, the patient’s sample is characterized for the presence of collateral sensitivity to various antibiotics and/or the genome analysis is carried out. These results flow directly back into the patient management to achieve elimination of the pathogen in the individual patient with the best possible cure rate. This individual application of the results of fundamental research in clinical practice is still very unusual in medicine.

 

What does the research area contribute to precision medicine in chronic inflammation?

The model diseases of COPD and tuberculosis are among the most significant lung diseases worldwide. CD-3 will develop individualized treatments for patients with COPD and tuberculosis, based on a systems understanding of the disease. The new approaches to treatment consider patient-specific information about the pathogens and their evolution in order to optimize the treatment’s success via individual treatment.

 

Cooperation with other research areas in the cluster

CD-3 cooperates with the following areas:

  • RTF II (evolutionary medicine, use of evolution experiments for the evaluation of new antibiotic treatments)
  • RTF IV (experimental models for the investigation of pulmonary infections and the influence of antibiotic treatment on the evolution of resistance)
  • RTF VI (sequence analysis)
  • RTF VIII (mathematical modeling of the evolution of resistance to different antibiotic treatments)
  • RTF IX (ethical and economic issues of alternative antibiotic treatments)
  • TI-1 (analysis of the relationship between the microbiome and inflammatory diseases, here taking the use of antibiotics into account).

Members

Prof. Dr. med. Thomas Bahmer

Full member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. Roland Diel

Full member

LungenClinic Großhansdorff

Prof. Dr. rer. nat. Andre Franke

Full member

Kiel University
Institute of Clinical Molecular Biology
Genetics & Bioinformatics

Dr. Anette Friedrichs

Full member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. Torsten Goldmann

Full member

Research Center Borstel - Leibniz Lung Center
Pathology
Medicine

Dr. med. Espen Elias Groth

Associated member

LungenClinic Grosshansdorf
Section Pneumology

Prof. Dr. rer. nat. Robert Häsler

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Jan-Bernd Hövener

Full member

MOIN CC
Department of Radiology and Neuroradiology
Biomedical Imaging

PD Dr. Barbara Kalsdorf

Full member

Research Center Borstel - Leibniz Lung Center
Medical Clinic Borstel

Prof. Dr. Dr. h.c. Christoph Lange

Full member

Research Center Borstel - Leibniz Lung Center
Medical Clinic Borstel

Prof. Dr. Matthias Merker

Full member

Research Center Borstel - Leibniz Lung Center
Evolution of the Resistome
Priority Research Area Infections

Prof. Dr. Stefan Niemann

Full member

Research Center Borstel - Leibniz Lung Center
Molecular and Experimental Mycobacteriology
Priority Research Area Infections

Prof. Dr. Klaus F. Rabe

Full member

LungenClinic Grosshansdorf
Section Pneumology

PD Dr. Norbert Reiling

Full member

Research Center Borstel - Leibniz Lung Center
Microbial Interface Biology
Priority Research Area Infections

Prof. Dr. med. Philip Rosenstiel

Full member

Kiel University
Institute of Clinical Molecular Biology
Molecular Cell Biology

Prof. Dr. Jan Rupp

Full member

UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology

Prof. Dr. Ulrich Schaible

Full member

Research Center Borstel - Leibniz Lung Center
Cellular Microbiology
Priority Research Area Infections

Prof. Dr. rer. nat. Alexander Scheffold

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. rer. nat. Ruth Schmitz-Streit

Full member

Kiel University
Institute of General Microbiology
Molecular Biology of Microorganisms

Prof. Dr. Hinrich Schulenburg

Full member

Kiel University
Institute of Zoology
Evolutionary Ecology and Genetics

PD Dr. Dominik Schwudke

Full member

Research Center Borstel - Leibniz Lung Center
Bioanalytical Chemistry
Priority Research Area Infections

Dr. Michael Stolpe

Full member

Kiel Institute for the World Economy
The Global Health Economy

Dr. med. Florian Tran

Associated member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. Arne Traulsen

Full member

Max Planck Institute for Evolutionary Biology
Evolutionary Theory

Dr. Leif Tüffers

Associated member

UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology
AG Prof. Rupp

Dr. Daniel Unterweger

Full member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine