Antimicrobial resistance (AMR) occurs when microorganisms survive exposure to an antimicrobial compound that should have killed them or halted their growth. This results in surviving generations of resistant microorganisms, not only due to resistance to the compounds but also to a lack of competition from other strains that did not survive the exposure. Mutations in the microorganism’s genetic material, together with selection pressure from antibiotic use, can lead to resistance due to the competitive advantage of those with the mutation.
However, resistance mutations are increasingly being found on extrachromosomal DNA, e.g. bacterial plasmids, enhancing the transmission of resistance across strains. Although resistance is a natural phenomenon, its spread and rate of occurrence has been enhanced by over- and inappropriate use of existing antimicrobials, the growing regularity of global travel and trade, and movement of disease-carrying vectors outside of their usual habitats.
The scale of the issue
In a recently published review, an estimated 700,000 people a year die because of AMR. This was considered a conservative estimate and, by 2050, if AMR continues unchecked, the estimate rises to 10 million deaths per year.
There are many examples of resistance in human and livestock medicine, e.g. the emergence of methicillin-resistant Staphylococcus aureus (MRSA). Speaking during a session on AMR as part of the British Society of Animal Science’s (BSAS) 2017 annual conference, Professor Brendan Gilmore, Queens University, cited lack of new and emerging antibiotics, as well as the departure of most of the major pharmaceutical companies from antibiotic research and development as a major issue in the AMR problem. He highlighted the fact that no new class of antibiotic has made it to the market in the past 30 years and there is a critical unmet need to address the loss of efficacy of conventional antibiotics. The most promising of potential antibiotics was recently rejected by the FDA after Phase III trials due to concern over hepatotoxicity.
Antimicrobial resistance is a global issue and use of antibiotics is predicted to rise globally by an average of around 4 percent. However, the range of increase/decrease is substantial. Countries, such as Brazil, India and China are set to increase antibiotic use by 17, 51 and 37 percent, respectively, yet other countries will see a decrease.
Tackling AMR requires a global, holistic approach, including the generation of new classes of antimicrobial compounds. According to Gilmore, major funding is required to develop new generations of antibiotics, alternative and adjuvant therapies and development of a viable business model for this research and development is critical.
Tackling AMR in livestock industry
While AMR is not a significant clinical issue in livestock production, there is much debate about the use of antimicrobials in livestock production. At the same conference, Professor David Barrett of the University of Bristol gave an idea of the scale of use of antimicrobials. He cited that, in the U.K., approximately 45 percent of prescribed antimicrobials were for use in animals, yet animals contribute 2.4 times the biomass of humans.
There is a tendency for livestock agriculture to bear the brunt of the blame for rising AMR, yet the transfer between animals and humans is not well understood and works both ways. Much emphasis has been placed on transfer of resistance from animals to humans via the food chain, but Barrett argued that this could be an over-emphasis and the environmental aspect needs also to be considered, for example, water course and pasture contamination.
However, Barrett emphasized that, whatever the transfer routes, there is sufficient science-based evidence for a reduction in antimicrobial use in the livestock production sector. He went on to say that, despite, ultimately, this responsibility being with veterinary surgeons due to their ability to prescribe medications, everyone linked to livestock production from farmers to retailers should be responsible for the appropriate use of these compounds. For example, under-dosing due to inaccurate estimation of liveweight or for financial saving aids in the development of resistance.
Barrett’s AMR Force research group at the University of Bristol has demonstrated that appropriate management can reduce and eventually eliminate the need for critically important antimicrobials, such as fluoroquinalones and third and fourth generation cephalosporins without compromising health or performance. Antimicrobial stewardship policies were created as part of individual farm management system by groups of dairy producers and their veterinarians, who worked together to develop their own AM stewardship policies leading to changes in farming practice and reduced AM use.
The policies were generated around four key principles:
- Disease reduction strategies
- Correct use of medicines
- Avoiding prophylactic use
- Quality data recording and use
The authors concluded that this study demonstrates the potential for producers to generate and implement tailored AM stewardship schemes to address the AMR challenge, without compromising the sustainability of the operation.
The U.K.-commissioned “Review on Antimicrobial Resistance” report by Jim O’Neill highlights the reduction of unnecessary antimicrobials in agriculture and their dissemination into the environment as one of the specific steps to tackling AMR by reducing demand. They also cite improvements should be made in monitoring the consumption by animals and humans.
Ultimately, it is in the global population’s interest to eliminate inappropriate and misuse of antimicrobials in human and veterinary medicine.
References available upon request.
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