Pig antimicrobials update—what is going on in EU?

Antimicrobial agents remain an issue in the EU because despite the in-feed ban of growth promoting antibiotics, total usage of such products remains high, according to authorities in many countries. The following interview highlights the latest thinking and developments on this topic.

Treatment instead of prevention may actually increase antibiotic resistance.
Treatment instead of prevention may actually increase antibiotic resistance.

Antimicrobial agents remain an issue in the EU because despite the in-feed ban of growth promoting antibiotics, total usage of such products remains high, according to authorities in many countries. The following interview highlights the latest thinking and developments on this topic.

Why has antimicrobial resistance become such a critical issue? 
Simply, human medicine is running out of antibiotics to treat a variety of infections. Despite continuing improvement in medical technology, doctors remain under tremendous pressure, especially in the hospital environment, to keep patients alive when normal antibiotic treatments fail. 

For example, methicillin-resistant Staphylococcus aureus (MRSA) has become a major problem in some countries, especially compounded by a decline in hospital hygiene. Vancomycin resistant enterococci (VRE) have also been on the increase and now carbapenem-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas species are appearing. The 3rd and 4th generation cephalosporins were frontline antibiotics and the carbapenems, which are also beta-lactam antibiotics but superior, were drugs of last resort. 

When resistance develops, there is very little left to use, and the doctors have major problems. This carbapenemase resistance has been seen in Europe especially in Greece and Italy, and increasingly in the UK, in patients coming in from Asia, where antimicrobial controls are considered less stringent than in the EU.

On the veterinary side, we have seen a steady increase in the use of 3rd and 4th generation cephalosporins over the last 15 years. As a result, we have seen the development of MRSA in pigs, which is well adapted to survive in the pig but fortunately not in man. MRSA has spread extensively throughout pig herds in the EU, North America, and China. 

We are starting to see an increase in extended-spectrum beta lactamase (ESBL) producing bacteria, such as Salmonella species and E. coli, as a result of 3rd and 4th generation cephalosporin use in pigs, particularly in the US but to a much lesser extent in the EU, where, surprisingly, broiler chickens had the highest incidence.

As a result, there is tremendous fear, that the resistant animal bacteria may become a reservoir for human resistance and make the situation worse. There is much agreement now that this risk is relatively small in comparison with the widespread hospital and community use of antibiotics by doctors who use mainly different antibiotics to veterinarians as shown in Figure 1.

Transmission, albeit at a low level, can occur (see Figure 2) via direct pig contact or improperly cooked food. However, government and professional institutions are carrying out a major review of antimicrobial resistance in both veterinary and human medicine. 

What will be the implications for the use of antimicrobials in pig veterinary practice? 
At this stage we do not know. In November 2011, the European Commission came out with a 12-point plan, but the details have not been published for consultation, yet. When the impact assessments of proposed changes are completed, the first drafts will be seen. Currently, predictions extend from Q3-Q4 2013.

If we look at the Danish model, it could have a major impact on antimicrobial use in pig medicine. It is very difficult to get medicated feed using premixes made up. Oral powders, followed by injectables are the most common treatment approaches. There has been dissociation between veterinarians prescribing and supplying medicines, so that medicines are supplied by pharmacists and veterinarians are not therefore encouraged to oversupply by making a profit.

Third and 4th generation cephalosporins and fluoroquinolones have been voluntarily withdrawn from use. There is a system of monitoring antimicrobial use both at a farm and veterinarians level with set baseline levels of usage. If a farmer or veterinarians goes above these levels, they are issued with a ‘yellow card’ warning and if they persist, the farmer and the vet receive increased inspections by the authorities. The EU Parliament has called for a ban on the prophylactic use of antibiotics.

Many people in Europe feel these measures are excessive. It is thought that further controls over antimicrobial usage will be put in place in the EU but many feel that the vet is still the best person to control and manage the use of antimicrobials responsibly, as has been demonstrated in the Netherlands, with a 50 percent reduction in use.

This has been the major thrust of national and EU bodies and the European Platform for the Responsible Use of Medicines in Animals (EPRUMA) has been set up. Some countries strongly support the use of premixes for medicated feed, like the UK, as it is a well-controlled method of medicating large numbers of animals in a herd. 

A number of countries have voluntarily stopped using the 3rd and 4th generation cephalosporins and fluoroquinolones, especially in poultry. Some others have substantially reduced their use in pigs and ruminants by restrictive prescription limits. Generally, it is felt that the complete banning of antimicrobial products or families would have a negative impact on animal health and certainly future drug development but their future use should be justified only after culture and antibiotic sensitivity testing. 

Once lost, these families of antibiotics will not be available again. There is likely to be an introduction of antimicrobial use monitoring at a farm and vet level, and a number of countries are introducing systems, such as Germany. This will add to the cost and bureaucracy of production but on the positive side, antimicrobial use can then better be correlated with antimicrobial resistance and may prove that antimicrobial resistance in swine is not such a problem for human health. It will lead to a more rational use of the older, less controversial antibiotic molecules, such as the aminopenicillins, tetracyclines, or sulphonamides particularly, for front line therapy.

Is prophylactic use essential in modern pig production?

Preventive use of antimicrobials is where the main controversy lies. For pig producers it is an essential method of controlling disease. If your pigs have Streptococcus suis meningitis, they are likely to have it in the next batch, as farms are endemically infected. It is only common sense to try to prevent it occurring with the use of penicillin or amoxicillin, where there is little or no resistance. 

Similarly, with swine dysentery, if a farm is infected with Brachyspira hyodysenteriae you try to prevent its spread into subsequent batches. To wait until the pigs breakdown with the disease and then having to treat them causes the animals pain and unnecessary suffering and may result in their death. Surely this cannot be good health or welfare management? In addition, repeated treatments of clinical cases are more likely to lead to resistance development, as we have seen in hospitals.

When can we expect to have harmonized guidelines regarding the prudent use of antimicrobials in the EU?

The guidelines for prudent or responsible use are already in bodies such as EPRUMA, but when will the EU Commission come out with their directives making them law, is a different matter. The EU Council (Heads of Member States) have come up with some good recommendations to support the Commission proposals. However, the EU Parliament may prove to be the stumbling block, as they can veto Commission proposals. We may not see the Commission proposals until later this year and it may take a number of years before they are law.

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