Research networks focus on investigating spread of antimicrobial resistance in humans, animals

May 12 2017

"Antimicrobial-resistant bacteria pose a complex challenge. This is why Germany, with its German Antimicrobial Resistance Strategy DART2020, is making sustained efforts to protect the health of humans and animals", says BfR President Professor Dr. Dr. Andreas Hensel. "In the spirit of the One Health strategy, this calls for interdisciplinary research by veterinarians and experts in human medicine as well as molecular biologists and epidemiologists, as successfully demonstrated by the RESET and MedVet-Staph network projects."

Since 2010, these research networks have been investigating the development, spread and mechanisms of resistance to certain antibiotics in cases of Escherichia coli and Staphylococcus aureus in humans and animals. Alongside the BfR, numerous universities and scientific institutions in Germany are involved in the network projects.

The RESET network investigates resistance to the particularly important antibiotic classes of cephalosporins and (fluoro)quinolones in intestinal bacteria such as Escherichia (E.) coli.

Some strains of these bacteria can destroy cephalosporins. In this process, they use enzymes known as "extended-spectrum beta-lactamases" (ESBLs) and AmpC beta-lactamases (AmpCs). The strains can pass on this destructive capability to other bacteria. Analyses conducted in the RESET network have shown that ESBL- or AmpC-producing E. coli are widespread in livestock. These bacteria were detected in all investigated poultry-rearing businesses. They were also found in 85% of investigated pig production and dairy cattle businesses as well as in 70% of cattle production businesses. Moreover, E. coli and Salmonella that can additionally destroy carbapenems were found in livestock in Germany for the first time. These antibiotics are used in hospitals to treat infections with multi-resistant bacteria.

The administration of antibiotics is not always responsible for the occurrence of resistant bacteria. E. coli that produce ESBLs or AmpCs also occur in groups of animals (in particular in broilers) that have had no contact with antibiotics. The bacteria and resistance genes can be transferred along the production chain and be transmitted to other foods in the kitchen.

In studies, ESBL-E. coli were found in 6.3% of the healthy general population and with similar frequency among pig farmers. In German hospitals, the share of ESBL-positive E. coli and Klebsiellae among all hospital acquired infections with these enterobacteria increased from 11.9% to 15.4% between 2007 and 2012.

Overall, the molecular biology analyses showed that various ESBL-forming bacteria possess the ability to be exchanged between humans, animals and their environment. Direct transmission of the bacteria with their resistance genes is evidently relatively seldom. Nevertheless, the resistance genes can be exchanged between different bacteria, and this makes it more difficult to trace them. It is therefore currently not possible to exactly assess the significance of livestock for the colonization and infection of humans with ESBL- or AmpC-forming enterobacteria.

RESET coordinator Professor Dr. Lothar Kreienbrock at the University of Veterinary Medicine Hannover says: "Our newly created joint database enables us to perform overarching analyses of both the data on the origin of samples from humans, animals, food and the environment as well as the data on the properties of the bacteria strains. Based on this joint strain and data collection, for example, we have succeeded for the first time in detecting the transmissible colistin resistance gene (mcr - 1) in E. coli from German livestock." He adds that the task now is therefore to further extend and consolidate these options developed together with the German Research Platform for Zoonoses and the TMF (technology and methodology platform for interconnected medical research) in the spirit of the One Health strategy.

The MedVet-Staph network focuses on the importance of the transmission of antimicrobial-resistant staphylococci including the methicillin-resistant Staphylococcus aureus strains (MRSA) between animals and humans. MRSA colonises around 0.8% of healthy people in the general German population (mostly in the nasal or throat area). By comparing the genetic fingerprint, it is possible to distinguish livestock-associated MRSA types from MRSA typically found in hospital acquired infections. Network coordinator PD Dr. med. Robin Köck from the University of Münster says: "The findings of the MedVet-Staph network have underlined that the transmission path between animals and humans is something that it is essential to bear in mind if we want to understand the spread of MRSA. We have shown that in particular direct contact with MRSA-carrying livestock, as occurs with farmers or vets, constitutes a high risk for transmission. More than 80% of farmers involved in pig production carry the bacterium."

MRSA is found with increasing frequency as a wound infection pathogen not only in livestock but increasingly also in horses, cats and dogs. The MRSA detected in these animals differs from the MRSA in livestock, however.

During the course of the project, it was not only MRSA but also other bacteria that were detected in livestock and farmers - bacteria such as enterococci and coagulase-negative staphylococci, which are resistant to substances such as linezolid or daptomycin - which are used in human medicine as reserve antibiotics. Further research is therefore necessary on the occurrence of antimicrobial-resistant bacteria in livestock and food as well as in pets and the environment.

The MedVet-Staph research network also investigated the extent to which livestock-associated MRSA can lead to disease in humans. The frequency of livestock-associated MRSA clones has increased overall in Germany, although there are marked regional differences: in individual regions with intensive livestock farming (in the northern region of North Rhine-Westphalia, for example), these bacteria are responsible for over 10% of severe MRSA infections in humans.

However, not all cases of detection in humans can be attributed to direct contact with positive animals. The MedVet-Staph network proved that 38% of the people in rural regions colonized with livestock-associated MRSA types had no direct contact with livestock. It must therefore be assumed that the bacteria are also passed on via other routes (e.g. human to human). According to research findings of the BfR and from Denmark, there are similarities between MRSA from poultry meat, in particular, turkey meat, and bacteria isolates from humans. This suggests that, in individual cases, livestock-associated MRSA can also be transmitted to humans via food. Experimental studies with broiler meat were conducted at the BfR in this regard. It was shown that the processing and preparation of contaminated food in domestic kitchens can result in the migration of MRSA and ESBL-forming E. coli to other foods which are then consumed by people without further heating. At the same time, however, the significance of this transmission path appears to be relatively minor.