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Antimicrobial Resistance
- Reducing the Over-Use of
Antibiotics.
Institute of Food Science and
Technology, Spring Conference;
18/04/2013
Jeff Jones, Animal Health and Veterinary
Laboratories Agency, UK
• Usage of antibiotics
• Spread of and selection for
antibiotic resistance genes and
antibiotic resistant bacteria
• Reducing the use of antibiotics
The use of antimicrobials in animals.
• Treatment of animal bacterial disease.
– Animal Health.
– Animal Welfare.
• Use of antimicrobials for growth promotion
purposes was banned throughout the EU
in 2006.
Some veterinary issues are similar to
those in human medicine...
• Bacterial diseases can usually be treated
with antibiotics.
• Viral conditions do not respond to antibacterials and so treatment of
uncomplicated viral conditions with
antibiotics is inappropriate.
Other similar Issues in human and
veterinary medicine...
• Prophylaxis.
– Animals or humans are treated before a
situation in which disease or infection is
highly likely to occur e.g. administration of
antimicrobials before intestinal surgery.
• Metaphylaxis.
– Animals or humans are treated which have
been in-contact with diseased animals or
humans and might be expected to be
incubating or have contracted the same
condition e.g. meningitis
The problems in man and animals are
not all linked...
• Human medicine.
– Many of the resistance problems in human medicine
are entirely due to the use of antimicrobials in people
and have little or nothing to do with antimicrobial use
in animals.
– Resistance in Mycobacterium tuberculosis.
– Resistance in the human pneumonia pathogen
Streptococcus pneumoniae.
• Veterinary medicine.
– Brachyspira hyodysenteriae (swine dysentery).
Zoonotic bacteria.
• Salmonella.
• Campylobacter.
Resistant strains of zoonotic bacteria
occurring in food-producing animals can
be transferred along the food chain to
humans.
Commensal bacteria.
• Escherichia coli.
• Enterococcus spp.
Resistant strains of commensal bacteria occurring
in food-producing animals can form a reservoir
of resistance genes which may transfer to other
bacteria.
Use of antimicrobials is one of the factors
which encourage the spread of
antimicrobial resistance…
• Use of Antimicrobials.
There are other factors including:
• Clonal spread of resistant bacteria.
Usage of veterinary antibacterial
agents
• In 2007, usage varied from 18 to 188 mg/kg
biomass of food producing animals across 10
European countries
• Highest usage of antibacterials is in pigs
• Differences between countries not explained
by differences in animal species
Grave et al, 2010
Any use of antibiotics will select resistant bacteria….
Resistant bacterium
in a population
Susceptible bacteria
killed by antibiotics;
resistant bacterium
has advantage
Resistant bacterium
survives to reproduce
General bacterial organisation:
•
•
•
•
A resistance gene.
A plasmid carrying the resistance gene.
The bacterial chromosome
The bacterial isolate.
Plasmids.
• Plasmids are circles of DNA able to transfer
genetic material between bacteria at conjugation
(bacterial mating).
• They provide a mechanism by which resistance
can spread between different strains of bacteria.
• Therefore, if a human ingests a strain of animal
E. coli, it may survive transiently and transfer its
resistance to human E. coli (which are adapted
to live in the human intestine for a long time).
Basic principle – Genetic linkage and coselection.
Tetracycline
Cephalosporin
Apramycin
Use of any one of these antimicrobials selects for
resistance to all three compounds….
Salmonella Heidelberg in Canada.
• In 2004 all the hatcheries in Quebec were
using ceftiofur to control E. coli infections.
• In 2005, all the hatcheries stopped using
ceftiofur
• within a year there was a dramatic drop in
the proportion of ceftiofur resistant E. coli and
S. Heidelberg from poultry and a drop in the
proportion of resistant S. Heidelberg from
humans.
Effect of withdrawal of ceftiofur use?
Dutil et al, 2010
16
Salmonella…
• The clonal spread of bacterial strains can be
very important in influencing the spread of
resistance
• Especially important within the pyramidal
structure of parts of farming (for example poultry
production).
• Resistant strains can spread independently of
antimicrobial usage.
A current example…..Salmonella
Kentucky.
• International spread of S. Kentucky ST198 –
increasing human cases from 2002-2008 in four
EU MSs and the US. Clonal spread occurred,
mainly related to travel of people to Middle East
and Africa. [Le Hello et al, 2011)
• In 2011 unexpectedly appeared in turkeys –
Poland. No clinical signs in turkeys.
• Also recovered from:
– Turkey meat
– Municipal sewage sludge (considered to
indicate spread to humans).
Salmonella Kentucky (2).
• Shows multiple drug resistance to 7 antibiotics
including ciprofloxacin.
• Isolates unusual in that they show high level
resistance to ciprofloxacin.
• Ciprofloxacin resistance is linked to three
mutations.
• Turkey isolates and those from human cases
are indistinguishable.
• Primary infection of turkeys may have been
outside Poland as most fattening flocks are
imported as day old birds or hatching eggs.
Salmonella Kentucky (3).
• Also occurs in poultry in some North African
countries.
• Little or no poultry movement from Africa to
Europe.
• ? Transferred to European poultry via humans?
• Confirmed in the recent case of a turkey farmer
in France who contracted the infection on
holiday in North Africa and transferred it to his
livestock...
Critically-Important Antimicrobials –
WHO, 2007
Quinolones /
fluoroquinolones
3rd / 4th generation
cephalosporins
Cascade (Off label) use of third and fourth generation
cephaloporins has now been banned in poultry
(including eggs) due to the risk of spread of
antimicrobial resistance to humans.
How do we reduce the use of antibiotics?
• Adopt alternative strategies for the control and
prevention of bacterial diseases of animals…
– Vaccination. This has (for example) dramatically
reduced the usage of antimicrobials in farmed fish.
– Animal Health Planning including disease eradication.
– Adopt alternative strategies eg teat sealant rather than
dry cow antibiotic in dairy cows.
– Improve hygiene and husbandry to reduce the
occurrence of certain diseases, for example bovine
and porcine respiratory disease can be influenced by
ventilation and building design.
How do we reduce the use of antibiotics?
• Ensure adequate farm and national
biosecurity measures are in place to
prevent the importation of resistant
bacteria from
– Neighbouring farms.
– Other countries.
Free trade, widespread global movement of
animals, people, products can allow rapid
dissemination of organisms….
How do we reduce the use of
Antibiotics?
• Ensure adequate terminal hygiene and
disinfection procedures are put in place,
with all-in; all-out management so that any
resistant organisms do not persist on
farms.
How do we reduce the use of antibiotics?
• Adopt the prudent and responsible use
guidelines published by the Responsible Use of
Medicines in Agriculture (RUMA) Alliance in the
UK (other associations have similar guidelines in
other countries).
• OIE Guidelines have been published which
provide guidance for all OIE Member Countries
and list responsibilities of all those involved.
Key points.
• Antibiotics are important for animal health.
• Large variation in usage between countries.
• Use of antimicrobials is one of the factors
which encourages the spread of antimicrobial
resistance
• Methods for reducing need for antibiotic use
include good biosecurity, adoption of prudent
use guidelines, effective disinfection and
hygiene, improvements in management and
husbandry, and vaccination.
References
Dutil L, Irwin R, Finley R,et al. Ceftiofur resistance in Salmonella enterica serovar
Heidelberg in chicken meat and humans, Canada. Emerg Infect Dis 2010 Jan
[accessed 15.04.13]. Available from
http://www.cdc.gov/EID/content/16/1/48.htm
Grave K, Torren-Edo J, Mackay D Comparison of the sales of veterinary
antibacterial agents between 10 European countries J. Antimicrob. Chemother.
(2010) 65(9): 2037-2040
Le Hello S,Weill FX Guibert V,et al. Early strains of multidrug-resistant Salmonella
enterica serovar Kentucky sequence type 198 from Southeast Asia harbor
Salmonella genomic island 1-J variants with a novel insertion sequence.
Antimicrob Agents Chemother 2012;56:5096-102
Thank you for listening…..