Antimicrobial Resistance: a Critical Issue

Dr Krejci opened the discussion by asking Dr Burch why antimicrobial resistance has become such a critical issue in Europe.

He said: "Simply, human medicine is running out of antibiotics to treat a variety of infections. With the continuing improvement in medical technology, it is possible to perform a large number of increasingly complex technical procedures. However, there is also immunosuppression either following transplant surgery, chemo- and radiotherapy for cancer and of course human immunodeficiency virus (HIV) is still out there and the body cannot defend itself. So the doctors are under tremendous pressure, especially in the hospital environment, to keep patients alive."

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major problem in some countries, especially compounded by falls in hospital hygiene, he said. 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 their frontline antibiotics and the carbapenems, which are also beta-lactam antibiotics but superior, were their drugs of last resort. When resistance develops to them, there is very little left, which is safe 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.

Dr Burch continued: "On the veterinary side, we have seen a steady increase in the use of 3rd and 4th generation cephalosporins over the last 15 years and 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, and has spread extensively throughout pig herds in the EU, N. 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, he said, 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 vets (see Figure 1).

Figure 1. Comparison of human and animal use of antibiotics in the UK
(VMD, 2010)

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

Figure 2. Number of humans treated with antibiotics per 100,000 population and infections associated with pigs
(Burch, 2013)

Implications for the Use of Antimicrobials in Pigs

In response to Dr Krejci's enquiry about the implications for the use of antimicrobials in swine veterinary practice, Dr Burch said: "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."

Looking at the Danish model, Dr Burch said it could have a major impact on antimicrobial use in swine 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 a dissociation between vets prescribing and supplying medicines, so that medicines are supplied by pharmacists and vets 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 vet level with set baseline levels of usage. If a farmer or vet 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.

According to Dr Burch, many people in Europe feel these measures are draconian or 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 per cent 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, he explained. 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, continued Dr Burch. 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, accordng to Dr Burch.

Prophylactic Use of Antibiotics in Pig Production

"Is prophylactic use essential in modern swine production?" asked Dr Krejci.

Dr Burch replied that it is the preventive use of antimicrobials where the main controversy lies. For swine 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, he said, 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," he said, adding that, in addition, repeated treatments of clinical cases are more likely to lead to resistance development, as we have seen in hospitals.

Harmonised EU Guidelines

Dr Krejci asked when can we expect to have harmonised guidelines regarding the prudent use of antimicrobials in the EU.

"The guidelines for prudent or responsible use are already there in bodies such as EPRUMA," said Dr Burch, "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," added Dr Burch.

June 2013