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Call for responsible antibiotics prescription

Heidelberg University Hospital and the University Medical Centre in Mannheim are working hard to counteract the increase of antibiotic resistance. Strategies include a European-wide system for infection surveillance, the training of health professionals in the responsible use of antibiotics and the search for novel antibiotic substances in unconventional organisms.

“The risk of being infected by antibiotic-resistant pathogens in hospitals is a huge problem and efforts need to be made to reduce this risk,” said Dr. Roger Vogelmann of the University Medical Centre in Mannheim in an interview on a recent health programme shown on German TV (Telemed). The rising levels of multiresistant bacterial strains that are able to oppose the action of commonly used antibiotics is a particular cause for concern. According to the European Centre for Disease Prevention and Control (ECDC), the responsible use of antibiotics in hospitals and GP practices has never been more urgent than it is today.

The European EARS-Net surveillance network

Distribution of fluoroquinolone-resistant human-pathogenic E. coli bacteria in EU countries. © EARS-Net
The effective surveillance of bacterial resistances is a prerequisite for the effective control of antibiotic-resistant pathogens and the danger they pose to human health. This is important both on the national and the international level as pathogens can easily cross national borders. To counteract this situation, a network in which the clinical laboratories of the most important university hospitals in the European Union work together was initiated in 1998 with the aim of recording and evaluating findings on nosocomial infections (also referred to as hospital-acquired infections) and the occurrence of multiresistant pathogens in a central database. The network is called the “European Antimicrobial Resistance Surveillance Network” (EARS-Net) and is managed and coordinated by the ECDC in Stockholm, Sweden. It is a European network of national surveillance systems that upload information about infections and pathogenic bacteria of public health importance to the central interactive ECDC database TESSy (The European Surveillance System). The ECDC ensures that the data are validated according to uniform quality criteria, that trends in the occurrence and spread of microbial resistance over time and between different countries and regions are analysed and that a summary of the situation in different patient collectives and regions is provided. The protocols and results are made available to the member institutions. At present, the database stores data that are collected by the national networks from more than 1,400 European hospitals that provide services to an estimated population of 100 million citizens.

The Institute of Medical Microbiology and Hygiene in the Department of Infectious Diseases at Heidelberg University Hospital (medical director: Prof. Dr. Klaus Heeg) is a certified partner of EARS-Net and collects data in the Rhine-Neckar metropolitan region. The national surveillance systems collect data on the antimicrobial susceptibility of seven bacterial pathogens of public health importance in humans: Staphylococcus aureus, especially the methicillin-resistant S. aureus (MRSA) strains which are resistant to an entire class of penicillin-like antibiotics; Pseudomonas aeruginosa, a common bacterium that thrives in moist environments and primarily causes infections in immunocompromised patients; two Enterococcus strains that are common commensal organisms in the intestines of humans, but may cause life-threatening sepsis that is becoming increasingly difficult to treat due to the rise in antibiotic resistances; nocosomial Streptococcus pneumoniae and Klebsiella pneumoniae bacteria are major causes of hospital-acquired pneumonia. And last but not least they collect data on Escherichia coli bacteria whose pathogenic representative EHEC (enterohaemorrhagic E. coli) caused a serious outbreak of foodborne illness in Germany in 2011 (see article entitled “Human infectious diseases: new threats”).

New weapons against resistant pathogens?

Prof. Dr. Paul Schnitzler, Virology, Department of Infectious Diseases, Heidelberg University Hospital. © Heidelberg University Hospital

Due to the fact that bacteria are increasingly developing new metabolic pathways that make them resistant to the antibiotics used to treat a certain infection, new drugs are urgently required to counteract the situation. While fourteen classes of antibiotics became available for the treatment of bacterial infections in humans in the period between the discovery of the first antibiotic in 1935 and 1968, only five antimicrobial agents have been approved since then. However, none of these five antibiotics is effective against Gram-negative bacteria such as Pseudomonas, Klebsiella or E. coli. 

There is not much money to be made with antibiotics as they are only prescribed for a limited period of time, in contrast to drugs that are required for the long-term treatment of metabolic diseases and cancer. The pharmaceutical industry is therefore not overly interested in investing in research in a field that offers scant financial rewards. At present, research into antibiotics is therefore mainly carried out in academic settings. In order to increase the chances of identifying effective antimicrobials, the search for novel substances is no longer restricted to bacteria and fungi, but has been extended to unusual groups of organisms. For example, Dr. Stefan Zimmermann and Prof. Dr. Paul Schnitzler from the Department of Infectious Diseases at Heidelberg University are investigating the potential effects of propolis extracts against multi-resistant bacteria. Propolis is a resin that honeybees collect from botanical sources and use as a sealant for cracks and crevices in the hive. Some types of propolis have been shown to have antibacterial and antifungal activity. Dose-response profiles with purified, concentrated propolis extracts have shown that the resins are able to inhibit the growth or kill a number of clinically important bacterial strains, including streptococci and methicillin-resistant staphylococci. This finding suggests that the researchers’ propolis extract might be used for the development of alternative products for the therapy of microbial infections.  

New training programme: "Antibiotic Stewardship"

Electron microscope image of vancomycin-resistant enterococci (noscomial infection). © Centers for Disease Control and Prevention

Strict hygiene measures, beginning with thorough hand washing, effectively reduce the risk of infection in hospitals. In addition, the increase in microbial resistance to antibiotics can be counteracted to some extent with strategies for changing antimicrobial prescribing behaviour in order to ensure the efficacy of available antibiotics. With support from the German Federal Ministry of Health, the German Society for Infectious Diseases has initiated “Antibiotic Stewardship” (ABS) training programmes that focus on standards and guidelines for optimising the therapy of bacterial infections as well as measures for the responsible utilisation of antibiotics in hospitals and GP practices.

In Germany, 180 or so medical specialists have so far been trained as ABS experts, including PD Dr. Roger Vogelmann, senior physician and deputy director of the Department of Internal Medicine II of the University Medical Centre in Mannheim. Vogelmann, who is the first ABS expert at Mannheim University Hospital, pointed out that in comparison with other European countries, Germany falls somewhere in the middle of the rankings with regard to the use of antibiotics and the development of multiresistances. Although Baden-Württemberg is fairly well placed in comparison with other German states, antibiotics are also administered too early here, in excessive quantities and for too long.  

Assessing bacterial cultures in Petri dishes. © Heidelberg University Hospital

A particular problem is that broad-spectrum antibiotics are far too frequently prescribed. As they act against a wide range of disease-causing bacteria, they should only be administered in specific medical situations as a last resort, and not as first-line treatment. However, GPs often do not have the time and possibility to identify which bacteria have caused a certain disease, and therefore tend to prescribe broad-spectrum antibiotics in order to be on the safe side. In his role as ABS expert at Mannheim University Hospital, Vogelmann has set up a team of doctors, pharmacists and microbiologists with the goal of implementing ABS measures. Amongst other things, they are developing an easy-to-use decision support software that calculates appropriate therapies, suggests an appropriate antibiotic, dosage, length of treatment, as well as providing information about seats of infection and local or regional occurrences of antibiotic resistance. The programme is also designed to support GPs in their treatment decisions. The team hopes that their activities will contribute to preventing the development of multi-resistant pathogens, reducing the length of disease and decreasing mortality rates from infection. 

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