Did banning growth promoters have the desired effect of reducing the prevalence of resistant strains of potentially harmful organisms found in the pig being transferred to man? Recent findings (Danmap 2002, 2003) suggest that it did and why it is planned to ban the rest of the growth promoters by 31st December 2005 in the EU.
The Danes were very much the drivers in Europe with regard to banning growth promoters as they had seen very high levels of antimicrobial resistance in pigs and broilers of certain organisms that might be transmitted to man via meat consumption or direct contact. Two groups of organisms, which were not necessarily harmful in their host animals, were involved, campylobacter, which can cause acute diarrhoea in man and enterococci, which are associated with severe hospital-acquired infections in immuno-compromised patients.
Campylobacter infections in man were commonly treated with macrolide antibiotics such as erythromycin. Tylosin, which was used as a growth promoter in pigs at the time, is related to this family of antibiotics. Enterococci were different, they were not normally harmful in man or animals, but when the immune system was suppressed by chemotherapy for cancer or for transplants or infections, such as HIV, this organism could become life threatening. Two important growth promoters avoparcin and virginiamycin were related to vancomycin and the streptogramin antibiotics respectively, which were becoming increasingly important as the backstops for controlling these infections. Hence the risk of resistance being spread to man from animal use was seen as too great and the ban was introduced on the 'precautionary principle'. In Denmark they banned all growth promoters in March 1998, before the EU partial ban came into place in July 1999 but they have seen a worrying increase in the use of antimicrobials as therapeutics, to control a variety of diarrhoeas in pigs and necrotic enteritis in chickens.
Graph 1. Growth promoter and therapeutic antimicrobial use in food-producing animals in Denmark
The links from pigs to man were always rather tenuous. Campylobacter jejuni which causes over 90% of infections in man, is hardly found in pigs where Campylobacter coli predominates (over 90%). Additionally the macrolide resistance patterns in C. coli do not match those found in man and using genetic markers, the isolates of C. jejuni found in man are not related to those found in pigs but can be found in chickens, cattle, water, wild fowl and even beach sand (Burch, 2002). Not many families want to picnic on a pig farm or a field where pig muck has been spread. The level of resistance did fall from a high of 70% to around 30%. (See graph 2.) ![]()
Ref: Danmap 2003
Graph 2. Macrolide resistance of Campylobacter coli in pigs after GP ban
Enterococcus faecium, which is the dominant problem-causing enterococcus in man, has been linked directly to man and pigs but in healthy farm and slaughterhouse workers. However it is genetically different from those isolates found in man with hospital-acquired epidemic vancomycin-resistant strains, which have proven so dangerous. There has been a consistently steady fall in antibiotic resistance for the 3 major growth promoters since the ban. (See Graph 3.) Even lower levels of resistance found on pork meat, similar to the levels found in man, suggest contamination may come more from man or the processing environment rather than the pig. ![]()
(Danmap, 2003)
Graph 3. Antimicrobial resistance of Enterococcus faecium in pigs after GP ban
Therefore the banning of the use of growth promoters has had the desired effect of reducing antimicrobial resistance in pigs, but is unlikely to have solved the problems of antibiotic resistance in man, especially coming from the hospitals. There has also been an increase in macrolide use in pigs seen in Denmark and the UK (VMD, 2003), switching tylosin from a growth promoter to a therapeutic for ileitis, which has probably caused the plateau in macrolide resistance at the 30% level for E. faecium and C. coli. ![]()
(Danmap 2003)What should we expect when we also ban the remaining three growth promoters in the UK for pigs: probably not a lot? For growth promotion alone there are already new products such as potassium diformate and other acidifiers to replace them. As long as zinc oxide is retained, then post-weaning scours should be controlled. We have already seen an increase in tylosin for ileitis control. With the withdrawal of salinomycin, then the use of tiamulin and valnemulin, the most effective therapeutics for treating spirochaetal infections such as swine dysentery and colitis, should increase due to the removal of the risk of ionophore interaction and the opportunity to switch from lincomycin. This will have an additional benefit as the pleuromutilins are not used in human medicine, unlike the macrolides and lincosamides and therefore will not compromise antimicrobial therapy in man.
References:
Danmap 2002 (2003) Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. Editors, Emboorg, H-D. and Heuer, O.E., Danish Zoonosis Centre, Danish Veterinary Institute, Copenhagen, Denmark www.vetinst.dkBurch, D.G.S. (2002) Risk assessment - Campylobacter infection transmission from pigs to man using erythromycin resistance as a marker. Pig Journal 50, 53-58.
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