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Antibiotic resistance and pig production – is there a link?

The use of antibiotics in pigs, poultry and other livestock continues to cause controversy, both in politics and in the scientific world. Is there a link with resistance in human use and should their use be banned or severely limited, as is the case in some European countries? The issue is complex and opinions differ immensely. Here's a recap of the state of affairs.

Without doubt, the most discussed topic at the recent SafePork conference in Maastricht, the Netherlands (19 - 22 June 2011), was the issue of using antibiotics in pig production – or rather, the increasing amounts of doubts around the practice. Keynote lecturer Dr Dik Mevius, Wageningen University and Research Centre, introduced the theme of antibiotic resistance, only to be followed later that day by Dr Thomas Blaha, University of Veterinary Medicine, Hanover, Germany – who spoke about how to reduce the number of antimicrobials used in pig production.
The bottom line in their presentations: General concern about the theme of antibiotic resistance is growing, not only in western Europe, but worldwide. Even in the United States, traditionally a strong advocate of antibiotic growth promoters, last year the Food and Drug Administration (FDA) launched a draft guidance in favour of ‘judicious use’.In some European countries, the sense of taking action has grown even stronger. This may come to the distress of some as it is feared that decisions taken may be unnecessarily severe and they may have far-reaching consequences on livestock production as we know it. In a web of lobby groups and bias views, it is hard to distinguish between proper science and heart-felt emotion. This article is intended to get a clearer view on things.
1 How to define antibiotic resistance and what causes it?
Antibiotic resistance can be described as the phenomenon of certain bacteria, fungi or other micro-organisms, developing mechanisms to combat either one or various antimicrobial or antifungal compounds. These antibiotic resistance factors are a natural feature of most bacteria as they need these to survive and compete in complex environments like soil, where numerous bacteria and fungi are found together. The bacteria that do possess certain relevant resistance factors are simply ‘selected’ when antibiotics are used in livestock production, as these will live whereas the others die off (see Figure 1). It is fair to assume that this process accelerated when antibiotic usage grew in livestock production over the past decades.
2 Why is there such a strong controversy?
It is a puzzle with so many ingredients that it is almost impossible to prove a direct scientific link between use in livestock production and resistance occurring in human medicine. One of the main difficulties is that animal production tends to use different types of antibiotics than modern human medicine. In animals, there is a tendency to use ‘older’ antibiotics, such as tetracyclines. In human medicine, we use more fluoroquinolones, betalactams (cephalosporins) and other advanced penicillins (carbapenems). These have not been so extensively used in pig medicine – but there is some overlap.
3 Which antibiotic resistant bacteria are both found in humans and livestock?
The Methicillin Resistant Staphylo-coccus aureus (MRSA) bacteria is the best-known example. S. aureus itself is pretty harmless to humans – it can exist in a nose without being destructive, but when a person’s health is severely weakened it can cause infections elsewhere in the human body. MRSA was first found in the UK in 1959; since 2005, it has also been linked to the pig industry, when Dutch research showed that MRSA had entered the human chain through direct contact with pigs. Soon it was found that about 25% of pig producers carried MRSA bacteria, mainly CC398, not previously found in man. This sparked many researchers around the world to find out whether the bacteria can also be found on pig and other livestock producers around the globe. Research confirmed the connection in most EU countries, as well as in Canada and the USA.
In addition, known since 1983 are bacteria forming Extended Spectrum Beta-Lactamase (ESBL), an enzyme capable of disabling rather sophisticated antibiotics, like third and fourth generation cephalosporins and broad-spectrum penicilins, thus capable of affecting treatment in hospitals. Among these bacteria forming ESBLs are some types of Escherichia coli, Klebsiella pneumoniae, Salmonella species and Pseudomonas aeruginosa. In the UK, a first link was discovered at a Welsh dairy farm in 2004. Nowadays, however, the link here appears to be mainly associated with broiler production – and transmission occurs through food rather than contact. There are questions as to whether the ESBLs in humans are the same as in poultry. In addition, the view is taken that ESBLs may first appear in humans and then in animals, rather than the other way round.
4 Does the use of antibiotics in livestock lead to resistance to antibiotics when used in treatment of humans?
Theoretically this could be the case, but many wonder what proportion of clinical problems in humans, related to antibiotic resistance in medical situations, can be traced back to some previous usage of antibiotics in animals. An example could clarify this: About 50% to 100% of poultry carcasses are contaminated with Campylobacter, and they are commonly resistant (40%) to fluoroquinolones. Disease prevalence, however, of reported cases of Campylobacter in the UK is relatively low, below 0.1% of the population per year. Good cooking kills 99.9% of all bacteria, fortunately, so the relative significance of transmission via cooked meat is small. So what is the percentage of resistance caused by veterinary use?
The role of house pets is often overlooked in this context, as humans often show a closer companionship with them. Usage of antibiotics in those animals may play a greater potential role in human clinical situations than farm animals.
5 Still, legislation towards antibiotics is getting increasingly tight in several countries. What are the latest developments?
As is widely known, the European Union has forbidden the use of antibiotics as growth promoters as from 2006. Denmark had even preceded this with a ban as from 1996. As a consequence, disease pressure and mortality (especially in weaner and grower pigs) is known to have increased initially in some cases, causing a sharp rise in therapeutic use of antibiotics.
To better target the antibiotic use, Denmark has now introduced a yellow card system for pork producers. A card is given if producers fail to meet good or satisfactory farm practices and it involves additional veterinary controls at their own expense. One of these practices is that antibiotic usage should be below a critical limit, which is established as twice the Danish average. This is expressed in ‘antibiotic daily doses per year’ (ADD/Y), a value based on the amount of active substance in a drug. For each animal type, the guidelines work out differently. In addition, the Danish pig industry also agreed on a two year voluntary ban on the use of cephalosporins.
Recent figures by statistics agency VetStat suggest that the new system does lead to antibiotics usage reduction – although the Danish already had a relatively low usage. The decrease was noted in all types of antibiotics, so not only piglets, but also finishers and sows received less antibiotic treatment. In the Netherlands, where antibiotic usage has always been strong, a similar yellow card system is now considered, despite an overall gradual reduction in livestock production as from 2007. Other measures in the Netherlands include a ban on using medicated premixes, to avoid any risk of cross-contamination with regular feeds. Decoupling of prescription and sales of antibiotics is also being discussed. In various other EU countries similar developments can be observed.
6 Have there been studies providing a total approach?
In July 2011, two EU agencies (EFSA and ECDC) published an analysis of member state data from 2009, compiling the first joint EU report on antimicrobial resistance in zoonotic bacteria affecting animals, humans and food. The report, based on 2009 data, shows that a high proportion of Campylobac-ter in humans is resistant to a critically important antibiotic for the treatment of human diseases: ciprofloxacin, belonging to the fluoroquinolones group. In animals, a high or moderate proportion of Salmonella (in chickens), Campylobacter and non-disease-causing E. coli was also found to be resistant to this antibiotic. The report also presents antimicrobial resistance data for Enterococci. The report makes an important contribution to current work being carried out at European level and the findings will be considered by the European Commission as it develops its forthcoming proposals for action to fight antimicrobial resistance.
Four veterinarians on the future of antibiotics
Pig Progress spoke to a number of leading veterinarians and asked them two questions.Their answers can be found below. A. Is antibiotic resistance in micro-organisms in production animals alone a reason for concern? B. Will antibiotics in livestock production ever be banned?
David Burch, Octagon Services, UK:
A “There are several bacteria causing antibiotic resistance in pigs, the main being E. coli and Actinobacillus pleuropneumoniae. However, there are some other bacteria as well having this problem, e.g. Brachispyra hyodysenteriae, mainly in Belgium and Spain, (leading to swine dysentery). Zinc oxide has been very effective in combating E. coliin the UK over many years resulting in lower use of antimicrobials.”
B “I think – no. We simply need antibiotics in veterinary medicine and animal production. To some extent we can replace them but when confronted with sick or dying animals, our number one priority as veterinarians would be that we need to help them. We have to look after our animals – and for that we need antibiotics.”
Dr Arie van Nes, Department of Farm Animal Health, Utrecht University, the Netherlands:
A “There is a clear increase in the number of resistant strains. And it’s important to keep long-term effects in mind.
Those strains of bacteria that became resistant to e.g. chloramphenicol 18-20 years ago, are still resistant to the same types of antibiotics nowadays.”
B “Once more it’s important to distinguish between different types of use. When we are talking about use of antibiotics in individual cases – that will continue to exist. But when we speak of use on batch levels, I think there are steps to be made. I think the use on batch level can be and has to be controlled very tightly. An industry-wide approach however is needed here.”
Dr Steven McOrist, reader of veterinary infectious diseases, Nottingham University, UK:
A “The connection of antibiotic usage in farm animals and the important infectious bacteria they face is a direct one. The livestock industries of UK and other groups subscribe closely to the responsible usage of antibiotics alliance, which continues to promote careful and balanced usage guidelines.”
B “Any banning of antibiotics in livestock will have a clear and negative impact on food security. A reasonable supply of antibiotics and their judicious use by trained veterinary professionals is necessary for the health and welfare of the millions of livestock needed to feed all societies. Some nations have decided to severely restrict usage of antibiotics in farm animals – it is important that the many negative impacts on animal welfare and food security need to be carefully monitored.”
Dr Howard Hill, veterinarian, chief operating officer at Iowa Select Farms and veterinary spokesperson of the NPPC:
A “This depends on the type of antibiotics used. To make a blunt statement would be difficult; not all antibiotics work the same way. Generally one can see that more risk would occur with long use of antibiotics in low amounts rather than use it occasionally in treatment or control use.”
B “No, that would be ridiculous. That would mean going back to the Dark Ages. Even the people that want production enhancement to be banned still appreciate the important bacterial effect. It will not happen – it would be inhumane. We need to be treating sick animals and saving their lives.”



By Vincent ter Beek

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