The relationship between using in-feed antimicrobials and

antimicrobial resistance in human pathogens

Emeritus Professor Mary BARTON AO, University of South Australia, Adelaide, Australia

Antimicrobial resistance (AMR) in bacteria that cause infections in humans is at crisis point. The World Health
Organisation has declared antimicrobial resistance a major health crisis for the 21 st Century. In the 60 or 70
years that antimicrobials have been available we have moved from a situation where death rates from
infectious diseases had declined significantly back to a situation where we again have untreatable human
infections. The recognition that “we all swim in the same gene pool” (meaning that resistant bacteria and
resistance genes move readily between animals and between animals and humans – and vice-versa) mandates
that medical and animal health authorities work together to ensure that in the future we have antimicrobials
to treat human and animal infections. The use of antimicrobials as feed additives is a very controversial issue.
It was not questioned in the early days but now it is recognised that exposure to lower (sub-therapeutic)
concentrations of antimicrobials is an ideal mechanism for selecting bacterial strains resistant to that
antimicrobial. Use of antimicrobial growth promotants (AGPs) increased as intensification of livestock
industries increased but is now declining or non-existent in some countries. There seems to be a link between
response to use of AGPs and control of sub-clinical infections – such as necrotic enteritis in chickens and swine
dysentery and Lawsonia ileitis in pigs. Resistance in enteric bacteria carried by animals is directly influenced by
what is included in feeds and pre-mixes/feed additives. Prophylactic and therapeutic antimicrobials are also
included in animal feeds. For example fluoroquinolone resistance in campylobacter and salmonella is directly
linked to therapeutic use of fluoroquinolones in feed and drinking water to treat salmonella and respiratory
infections in poultry and other animals. Resistance to tylosin and erythromycin is widespread around the world
in livestock isolates of campylobacter reflecting the extensive use of tylosin in animal feeds (as an AGP,
prophylactically to prevent/control mycoplasma infections and swine dysentery and ileitis and therapeutically
for respiratory infections). Resistance to vancomycin in animal isolates of enterococci seems to have declined
around the world following withdrawal of avoparcin from the market. It is disturbing to see the recent report
of vanA VRE in pork samples collected at a Hong Kong slaughterhouse as this suggests that avoparcin is still
being used in China. Virginiamycin is an AGP that has been used extensively in animals. It is in the same
antimicrobial class as quinupristin/dalfopristin which was regarded as an important drug to treat MRSA and
VRE infections in humans. There is less concern about virginiamycin resistance now because of the
development of alternative human antimicrobials. Bacitracin is used topically in human medicine and it has
been used in some countries orally in humans to clear colonisation of the intestinal tract by VRE. This does
bring its use into conflict with animal use where zinc bacitracin has traditionally been used as a growth
promotant and as a prophylactic to control necrotic enteritis in chickens. Extended spectrum beta-lactamase
producing bacteria (ESBLs) are of particular concern in human medicine as the problem is increasing at a very
rapid rate. They are associated with the use of 3rd and 4th generation cephalosporins which should only be
used therapeutically. Ampicillin use too can select for a type of ESBL. Ampicillin/amoxicillin is widely used in
pre-mixes for pigs and poultry as a preventive for enteric infections. Non-microbial alternatives to AGPs are
clearly a high priority. In recent years there has been much research in this field including modifications to
feed ingredients and novel feed additives such as prebiotics, probiotics and plant extracts. Animal industries
(including aquaculture) need to take much more seriously the issue of antimicrobial resistance. There can be
no justification for continuing use of AGPs so alternatives must be further explored. Prudent use guidelines for
antimicrobials must be developed and implemented – not just for injectable therapeutic products but also for
in-feed products used for prophylaxis and therapy.