Nosocomial Infections: News from the Lab

23. May 2013

When patients only become sick in hospital and antibiotics are no longer effective, matters can become extremely dangerous and expensive. Researchers and physicians are trying to use different approaches to get on top of hospital infections.

Nosocomial infections are a problem – a big problem. About 400,000 to 600,000 such infections occur annually and about 7,500–15,000 deaths are associated with it. One danger in this respect is the development of multi-drug resistant germs, which can be life-threatening – especially for immuno-compromised patients or critically ill patients. While true that the situation regarding resistance with multi-drug resistant Gram-positive bacteria (Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus (VRE)) is better today than it was 10 years ago thanks to the introduction of new antibiotics, sooner or later resistance will however reappear. Therefore researchers are not only looking for new antibiotics, but are also thinking in other directions.

Specific vaccines ready in a few days

One example is the project guided by Prof. Dr. Andreas Wieser and Sören Schubert, both from the Max von Pettenkofer-Institute of Hygiene and Medical Microbiology (Ludwig-Maximilians-University of Munich). They have developed a method for producing specific vaccines against isolated pathogens in less than two weeks. Bacteria are removed from the sufferers and these are then genetically altered, propagated and finally, by means of a column-based method, purified and stabilised. The most tiny particles of bacteria form the basis of the vaccine. Such a formulation is particularly suitable for patients who have not yet been infected by the pathogen, but because of a lengthy or difficult treatment have to be in hospital for extended periods or may in addition be immuno-suppressed.

The extent to which the vaccine is effective in patients already infected has not yet been sufficiently clarified. “It is certainly no ‘silver bullet’ but maybe another way to protect some patients has been found”, says Dr. Wieser. In animal studies, the vaccine showed efficacy both as a nasal spray as well as in injection form.

“The new type of method, for which we have applied to obtain a patent, offers in both veterinary medicine and human medicine interesting perspectives. This is mainly through using the preventive option against increasingly resistant pathogens without being so quick to use chemical antibiotics. This could slow the development of resistance of pathogens and prevent unnecessary deaths. Everything is of course dependent on the speed of preparation and this can ultimately be assessed only after the final approval studies and after limitations are defined by the regulatory authorities”, Wieser emphasises.

Taking advantage of the vulnerability of the microorganisms

Another research approach in the treatment of multi-resistant pathogens is being pursued by Professor Dr. Günter Fritz of the University Hospital Freiburg. He and scientists in the U.S. with whom he has been working together have been able to show that our immune system actually holds an effective antidote against MRSA. The protein calprotectin, also known as S100A8/A9, is capable of inhibiting the growth of the pathogen by releasing immune cells at the site of infection and binding the metals zinc and manganese there. Manganese is required by many microorganisms for the manufacture of functional superoxide dismutase. “Using this enzyme the microorganisms defend themselves against reactive oxygen molecules which immune cells emit at the site of an infection in order to destroy the invaders. The trace element manganese is therefore vital to MRSA bacteria”, says Dr. Fritz.

He has now been able to discover the molecular mode of action of calprotectin in the binding of manganese and zinc, thus indicating a weak point of the microorganisms. These findings will now be used to develop novel compounds that bind manganese and are thus bacteriostatic, or to find ways to stimulate the immune system so that it can cope with the pathogens themselves.

Yet if the mechanism in the body is already there, why are medications then needed that do the same? Dr. Fritz explains this: “In infected patients, the pathogen has simply gotten the upper hand. This means that the immune system has not been able in a sufficiently effective and timely manner to set a defence against the pathogenic invaders. The complex formation using manganese and zinc ions via S100A8/A9 is one of the mechanisms with which our body tries to fix the invaders at the point of infection, until more of our immune defence mechanisms attack, such as production of specific antibodies.” Since S100A8/A9 is effective against many pathogenic microorganisms, Fritz sees the possibility that an appropriate agent could be applied broadly.

Primary objective: avoid transmission

It is particularly important however with hospital-acquired infections to prevent the transfer of potentially harmful microorganisms from patient to patient or staff-to-patient (and vice versa). Studies made on intensive care stations show that up to 38 per cent of hospital germs originate from other patients or caregivers, thus having an external cause. “In these cases we can through systematic identification of infectious problems prevent at least 20 to 30 per cent of infections, in some facilities even up to 40 per cent”, explains Professor Dr. Frank Brunkhorst of the Jena University Hospital as part of the Congress of German Society for Internal Medicine (DGIM). “That means in real terms up to 180,000 annual infections in Germany – including 4,500 deaths – are preventable.”

These are impressive numbers. In addition to some serious health consequences for affected patients, nosocomial infections also mean stress for the staff who have to carry out intensive care on these patients, and rising costs for the health system due to prolonged hospital stays.

ALERTS trial is testing measures for infection prevention

To reduce hospital infections, targeted infection prevention management is needed. That also costs money: money which, due to rising cost pressures in the health system, many hospitals often cannot afford. Prof. Dr. Brunkhorst as head of the Paul Martini Research Group for Clinical Sepsis Research University Hospital of Jena is coordinating the first hospital-wide prevention study (ALERTS), which is being funded by the German Federal Ministry of Education and Research (BMBF). It should demonstrate how prevention programs reduce rates of infection on a sustained basis. After a first phase, training of staff is now taking place. The most important point is hand disinfection; measures such as regular antiseptic mouthwashing for prevention of ventilation-associated pneumonia, adequate hair removal with trimmers before operations (in order to prevent skin damage and resulting infections) and many other evidence-based methods will be applied as a result. What the cost-benefit ratio for a clinic looks like in the end will only become clear after the end of the study and an evaluation in 2014.

However, Dr. Stefan Hagel, Director of the ALERTS study at the University Hospital Jena, points out: “There are studies showing that ventilation-associated pneumonia has an additional cost of EUR 17,000 and a prolonged stay in hospital of nine days as consequence.” It would certainly help if the patients were also to insist that a clinic have a good infection prevention program. If the rate of preventable hospital infections were a criterion for the selection of the hospital, the hospitals would see to the implement of a program more quickly.

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