Antibiotic resistance: recognising the need for change
Antibiotic resistance has the potential to become one of the greatest problems of our generation, given the ever-increasing rise in bacterial strains that are less and less sensitive to existing treatments. While abuse of antibiotics in humans is probably the major contributor, policy makers have turned the spotlight on agricultural use as a way to control the problem.
Treatment of animals with antimicrobials can cause drug resistance to zoonotic pathogens (e.g., Salmonella, Campylobacter) that can be transmitted to humans. Bacteria from animals can be spread to food products during slaughter and processing, and this spread has been extensively documented for conventional foodborne pathogens such as Salmonella, Campylobacter and E. coli.
Reliable data on antibiotic consumption and resistance is now quite easy to obtain. The European Union has implemented a coordinated approach to compiling relevant data since 2004. Within the EU, Sweden has had a monitoring program since the 1980s and Denmark, via the DANMAP program, has provided an efficient record of antimicrobial consumption in humans and animals. In general, the more antibiotics are consumed, the more antibiotic resistance is found, regardless of whether such use is for therapeutic or growth promotant use.
A review of the annual surveys on antimicrobial resistance issued by EFSA (The European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food) each year reveals some interesting, longer-term trends. Most notable is an increase in antibiotic resistance among Salmonella isolates in poultry (Figure 1). In particular and of concern for human health, there has been an increase in the resistance for Salmonella enteritidis the past few years (Figure 2).
Other trends indicate that the relative resistance rates for S. typhimurium remain static, but this should still be a concern due to the relatively high rates noted. The majority of antibiotic resistance can be noted among broilers and this may in part be due to the lower level of antibiotic use in the layer industry relative to the broiler market. The data also indicates a trend toward an increase in antibiotic resistance in Salmonella isolated from poultry meat since 2010. These temporal changes would need to be monitored for a longer period to determine the extent of this rise; however there is a relatively high rate among some classes of antibiotics, e.g. nalidixic acid, ciprofloxacin and the sulphonamides.
The data further indicates a high level of antibiotic resistance for Campylobacter sp., with temporal trends indicating a rise in resistance among specific strains and to specific antibiotics. Of particular interest is the rise in resistance to antibiotics such as nalidixic acid and ciprofloxacin in C jejuni and C coli in broiler meat. High level resistance to these antibiotics has been noted in the same strains when isolated from humans.
Figure 1 Antibiotic resistance in Salmonella isolates from poultry 2008-2014
Figure 2 Antibiotic resistance in Salmonella enteritidis from poultry 2008-2012
Figure 3 Antibiotic resistance patterns in C jejuni in Broiler meat (2008-2014)
While the debate rages over what is driving the seemingly inexorable rise of antibiotic-resistant microbes, alternatives to antibiotics and products capable of reducing the risk of antibiotic resistance transfer through the food chain are clearly required.
Globally it is recognized that there is no so-called "silver bullet" to replace antibiotic use in animal production and producers will almost certainly have to improve hygiene and husbandry to address the issue.
Products that will assist the move to antibiotic-free production status include many that are designed to regulate and support the gut environment and its microflora:
• Coccidial vaccines
• Competitive exclusion products
• Feed enzymes
• Functional nutrients such as nucleotides
• Organic acids and feed hygiene products
• Organic minerals
• Plant-based products such as herbs, spices and essential oils
• Yeast cell wall derivatives such as mannan-oligosaccharides (MOS) and Mannose Rich Fractions (MRF)
Of the functional ingredients currently in use for microbial control, mannan-oligosaccharides (MOS) and Mannose Rich Fractions (MRF) are widely used in animal nutrition and have been shown to improve animal performance in a manner similar to antibiotic-like growth promoters. Since 1999 the use of MOS in animal feed has become more prominent, mainly due to the European ban on prophylactic antibiotic growth promoters in animal feed. Given their ability to bind and limit the colonization of gut pathogens, MOS and MRF have proven to be an effective solution for antibiotic-free diets, as well as providing support for immunity and digestion.
Some newer studies have focussed on the effect of MRF supplementation on the overall bacterial community of the poultry gut and such work has shown that MRF supplementation can significantly alter the intestinal microflora (the so-called microbiome).
More strikingly, consistent alterations in specific components of the caecal microbiota of broilers have been identified with alterations also noted in numerous biological pathways as a result of supplementation with MRF.
One strategy to reduce or limit the use of antibiotics is to find ways to make them more effective and the use of MRF has been shown to enhance the sensitivity of bacteria to the effects of antibiotics and in doing so, reduce the minimum inhibitory concentration (MIC) required. Additionally, MRF supplementation to the diets of broilers has been associated with a decrease in selected antibiotic resistance gene copy number. This is potentially linked to the ability of MRF to induce plasmid loss, thereby reducing plasmid transfer between microbes (Table 1).
Table 1. MRF induces plasmid loss in selected gram-negative isolates
It is essential that antibiotic-free production systems improve overall feed quality as animals that are fed quality feeds are less susceptible to enteric problems. Ultimately this move from least cost feed formulation and reliance on antibiotics will be toward high quality feeds containing functional ingredients.
Programs which employ a holistic approach to health management have proven to be extremely effective. By utilizing a combination of strategies, producers can rehabilitate and accelerate the evolution of the intestinal microbiota. The success of these "Seed, Feed and Weed" programs is reliant on firstly seeding the gut with favorable microflora using a probiotic; feeding the favorable microbes through acids or enzymes and lastly, weeding out pathogens by using MRF products.
Concerns about antibiotic resistance among scientists, regulators and consumers has driven the EU ban on AGPs and been a catalyst for change in the U.S. This has heralded a global move to reduce antibiotic usage, and further ongoing changes in animal production systems are likely to be substantial. Ultimately what is required are innovative replacement products and alternative strategies. The use of functional feed components such as MOS and MRF represent one such innovative approach to break the cycle of resistance.
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Article made possible through the contribution of Richard Murphy Ph.D. and Alltech European Bioscience Centre