CD-3: Individualized antibiotic therapy for chronic lung infections

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

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).