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University Hospital of Ulm combines forces

The Comprehensive Infectious Diseases Centre (CIDC) at the University of Ulm, the only one of its kind in Germany, was recently presented to the public. The interdisciplinary centre, which combines six institutes and 16 hospitals, is responsible for coordinating the cooperation between hospital doctors, special laboratories and scientists in the diagnosis and therapy of highly complex infectious diseases. The German Federal Ministry of Education and Research (BMBF) is financing an interdisciplinary group of researchers with about €1.9 million in funding.

The core of the new centre is the weekly “infection boards”, interdisciplinary meetings of experts. “We use these meetings to discuss complicated cases of infectious diseases and to determine individual therapies,” explained Peter Kern, spokesperson of the CIDC and head of the Section of Infectious Diseases and Clinical Immunology at the University Hospital of Ulm. The objective of this and other BMBF-funded centres is to strengthen the interdisciplinary cooperation between scientists working in diagnosis and therapy, as well as the integration of state-of-the-art results from research and development.
The schematic shows the proposed interdisciplinarity of the centre. (Photo: University Hospital Ulm)
The schematic shows the proposed interdisciplinarity of the centre. (Photo: University Hospital Ulm)

Better treatment

Kern describes the benefit to patients as follows: “Based on therapy recommendations, we will develop general hospital guidelines, improve the quality of patient treatment and lay the foundations for specific research projects.” In addition, the new centre will offer a greater number of special infectious-disease related ward rounds in participating hospitals.

Infections are a serious threat to immunocompromised children

Paediatrician Michael Leichsenring (Photo: University Hospital of Ulm)
The new centre is particularly important for the field of paediatrics, said Michael Leichsenring, CIDC secretary and chief physician at the Department of Paediatrics and Adolescent Medicine at the University Hospital in Ulm, where acute bacterial or viral and fungal infections pose a very high risk to extremely premature babies or children with cancer who are undergoing intensive therapy.

“As the progression of such infections in immunocompromised children is characterised by many particularities, the close interdisciplinary cooperation between bacteriologists, virologists and clinical doctors is a prerequisite for successful therapy,” said Leichsenring.

50 per cent of all prescribed antibiotics are not necessary

Today, the specific and careful treatment of infections is more important than ever before. The former miracle weapons against bacterial infections, i.e. antibiotics, risk becoming ineffective as bacterial pathogens are becoming increasingly resistant to such drugs. Experts estimate that 50 per cent of all antibiotics prescriptions are unnecessary.

Experts warn of pandemics

Experts regard the current situation as dramatic and warn of a worldwide pandemic (British Medical Journal 2008;337:a1438: doi:10.1136/bmj.a1438). They believe that the success of modern medicine in surgery, organ transplants and cancer chemotherapy could be at risk if it proves impossible to effectively prevent and treat bacterial infections. The epidemiological report from the European Centre for Disease Prevention and Control, published in 2007, regards antibiotics-resistant microbes as the greatest health risk for the European population.

Globalisation, associated with the increasing speed of commodity flow and the growing desire to travel, also contributes to the rapid expansion of bacteria and bacteria resistance genes around the globe. Experts even fear a pandemic (“We are facing not only epidemics but pandemics of antibiotic resistance“, BMJ, ebd.).

Growing resistance but fewer new drugs

Peter Kern is the spokesperson of the new centre (Photo: University Hospital Ulm)
At the same time, Dr. Kern also laments the drop in the number of new antibiotics developed. This shortcoming is evident on a global level: As antibiotics lose their effect, the development of new substances in the pharmaceutical industry also decreases because the pharmaceutical industry is more interested in developing pharmaceuticals for chronic diseases. Between 1930 and 1960 more than a dozen new classes of antibiotics were developed whilst only two new classes have been developed since 1960. In the laboratories of big pharmaceutical companies, new antibiotics development only accounts for 1.6 percent of all development (BMJ, ebd.)

“The excessive application of antibiotics favours the development of resistances; on the other hand, the careful application of antibiotics can delay the onset of resistances, said Kern. For example, many doctors like to continue antibiotics treatment as perioperative prophylaxis in order to reduce the rate of postoperative infections, on the basis that one should “never change a winning team”, even though the administration of antibiotics is not necessary. Such patients have adjusted their entire bacterial repertoire to their specific antibiotics treatment; and if they then contract pneumonia, the antibiotics would not be effective, explained Peter Kern.
Ludwig Maier, Director of the Hospital Pharmacy: one in four euros is spent on anti-infective products. (Photo: University Hospital Ulm)
The new centre focuses on the development of “strategies for the specific and careful use of antibiotics in the hospital” (Kern). This is also of economic importance, explains Ludwig Maier, Director of the Hospital Pharmacy: “We are part of the implementation of the centre’s guidelines and therefore an important part of the centre’s efforts to develop rational and effective drug therapies.” Maier also said that anti-infective drugs account for a quarter of total costs.

A group of clinical researchers, funded by the BMBF, has a central position in the new interdisciplinary centre. The goal is to expand the Section of Infectious Diseases and Clinical Immunology at the University Hospital of Ulm. The researchers are involved in six projects dealing with the identification, prevention and treatment of infections in immunocompromised patients.

The researchers are focusing on the weakened immune system

Two core projects focus on the reconstitution of the immune system. Infectiologists, internal medicine experts, virologists and microbiologists are working together on the two interdisciplinary and closely connected projects. The Ulm researchers are focusing on the weakened immune system of patients after stem cell transplantation, antiretroviral therapy of HIV and after the treatment of autoimmune diseases with anti-TNFα (tumour necrosis factor) and other biologicals.

Kern uses HIV as an example to describe the problem: After therapy and the decrease in the viral load, viruses will begin to proliferate again if they cannot be controlled or kept in check. This is caused by the patients’ weakened immune defence system and also affects patients who have undergone bone marrow transplantation. Such patients have a “maturing immune system” that has to deal differently with the previously existing pathogens.

Vaccine investigation with a mouse model

In a phase I/II trial involving mice, researchers are testing whether a peptide vaccine against the human cytomegalovirus (HCMV) can be used for patients who have undergone allogeneic stem cell transplantation. This virus is omnipresent and is normally harmless to healthy people. Pregnant women, unborn children and people with weakened immune systems however are greatly affected by this virus, which is a member of the herpes virus family.

Researchers at the University Hospital in Ulm are also analysing whether complications are related to HCMV and HIV variants. In the long term, the researchers hope that insights into immunological deficits and their reversal will enable a more accurate risk estimation in patients where bacterial or viral pathogens are reactivated due to different therapies.

Hardly any clinical infectious disease departments at German university hospitals

According to Kern, interdisciplinary infectiology is "not very widespread" at German university hospitals. The University Hospital in Freiburg established an infectiology department as late as 2002; the University Hospital in Regensburg also managed to establish an infectious disease department with government funds. In many countries, infectiology is a recognised clinical priority for which specific courses are taught at universities. Only recently has Germany introduced the possibility for physicians to further their medical education in the field of infectious diseases. In contrast to Switzerland and Austria, Germany does not yet have infectious disease specialists (German: Facharzt für Infektiologie).

wp - 25 Sept. 2008
© BIOPRO Baden-Württemberg GmbH

Press conference of the University of Ulm, 24 September 2008
Annual epidemiological report on communicable diseases in Europe (https://www.gesundheitsindustrie-bw.deecdc.europa.eu/pdf/ECDC_epi_report_2007.pdf)
Otto Cars et al.: Meeting the challenge of antibiotic resistance, in: British Medical Journal 18 Sept. 2008 (doi:10.1136/bmj.a1438)
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/university-hospital-of-ulm-combines-forces