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  • Antimicrobial use and antimicrobial resistance

    Peter Smith

    peter.smith @nuigalway.ie

    Aquatic AMR Workshop 1: 10-11 April 2017, Mangalore, India

    FMM/RAS/298: Strengthening capacities, policies and national action plans on

    prudent and responsible use of antimicrobials in fisheries

  • Antibiotics are chemicals

    that kill or inhibit the growth of bacteria

    but

    have very much less effect

    on animals and plants

  • The availability of antibiotics

    produced a total revolution in our thinking about the

    control of infectious diseases

    We now had a “magic bullet”

    A drug that attacked invading bacteria but had no effect

    on the host

  • There was a problem with our

    ‘magic bullets’

    The more we used them

    The less use they were

  • If we are to protect our

    “magic bullet”

    we must learn how to use it

    We will have to learn the values of

    wisdom,

    prudence

    and

    restraint

  • We need to understand bacteria

    Bacteria are the oldest life form on this planet

    They have survived 4 billion years because they

    have a remarkable ability to adapt to changes in

    their environment

    They are protean

    Mutable, flexible, versatile, adaptable and capable of

    adopting many forms

  • Proteus

    A sea god in Greek mythology.

    He had to reveal the future but

    changed his appearance to

    avoid having to.

    He revealed the truth only to

    those who were wise enough to

    see through his shape-

    changing to his real nature

    https://www.google.ie/imgres?imgurl=https://upload.wikimedia.org/wikipedia/commons/1/1a/Proteus-Alciato.gif&imgrefurl=https://en.wikipedia.org/wiki/Proteus&docid=WhkSoNGN8-Rr0M&tbnid=Hv1lIGw1FXwDlM:&vet=10ahUKEwjSopu8wufSAhWlCcAKHWseBJgQMwggKAAwAA..i&w=220&h=232&bih=905&biw=1920&q=proteus%20images&ved=0ahUKEwjSopu8wufSAhWlCcAKHWseBJgQMwggKAAwAA&iact=mrc&uact=8 https://www.google.ie/imgres?imgurl=https://upload.wikimedia.org/wikipedia/commons/1/1a/Proteus-Alciato.gif&imgrefurl=https://en.wikipedia.org/wiki/Proteus&docid=WhkSoNGN8-Rr0M&tbnid=Hv1lIGw1FXwDlM:&vet=10ahUKEwjSopu8wufSAhWlCcAKHWseBJgQMwggKAAwAA..i&w=220&h=232&bih=905&biw=1920&q=proteus%20images&ved=0ahUKEwjSopu8wufSAhWlCcAKHWseBJgQMwggKAAwAA&iact=mrc&uact=8

  • Bacteria adapt to their environment

    If their environment contains a chemical agent that

    is harmful to them, bacterial populations will adapt.

    Strains and species that are not affected by that

    chemical will emerge.

  • ALL uses of antibiotics release these agents into the

    environment

    It is absolutely inevitable

    that bacteria will adapt to the presence of antibiotics in

    their environment

    The emergence of bacteria that can function in the

    presence of antibiotics will follow the use of antibiotics as

    night follows day

  • Where does ‘resistance’ come from

    Bacterial genes that encode reduced susceptibility to

    antibiotics existed before antibiotics were discovered,

    developed and used by humans

    The use of antibiotics by humans has resulted in a selective

    pressure for an increase in the frequency of bacteria

    containing these genes

    The use of antibiotics has also increased the range of species

    where these genes are found

  • Bacterial communication

    Within the microbiome genetic data including ‘resistance’

    genes are continually being exchanged

    All bacteria have access to their Google and Facebook

    They are continuously ‘on-line’

    Any ‘resistance’ gene present in any member of any species in

    the microbiome has the potential to transfer to any other

    species

  • GENERAL RULE 1

    The more

    antibiotics are used to control disease

    the more likely

    the target bacteria will be resistant

    and the less likely

    they will have any therapeutic value

  • GENERAL RULE 2

    The increase in the frequency of resistance genes anywhere

    on the planet increases the probability that a similar increase

    will occur anywhere else

    Antibiotic use in human medicine could impact the frequency

    of resistance genes in bacteria that infect aquatic animals

    Antibiotic use in aquatic animals could impact the frequency

    of resistance genes in bacteria encountered in human

    medicine

  • Use and resistance

    The relationship between

    use and the emergence of resistance

    is not simple or linear

    In some species resistance to some antibiotics emerged

    rapidly

    In others resistance appeared only very slowly

  • Percentage ‘resistance’ in Flavobacterium psychrophilum

    Denmark UK Chile USA

    Quinolones 76 82 40 0

    Oxytetracycline 40 54 56 76

    Florfenicol 0 0 1 0

  • The threat of re-entering the pre-antibiotic age

    The global rainbow trout industry is currently dependent on

    the continued susceptibility of Flavobacterium psychrophilum

    to florfenicol.

    All our experience suggests that this resistance will emerge

    sometime soon and then …………..

    During the furunculosis epizootic of the 1980s in northern

    Europe strains of Aeromonas salmonicida were isolated that

    were resistant to all available antibiotics

  • Avoiding the threat

    If we wish to avoid re-entering the pre-antibiotic age we must learn

    how to use antibiotics wisely

    1. Although we have very little idea about how much we use in

    aquaculture we do know that we must use less.

    2. We need antibiotics but we must learn to use antibiotics only when

    that use is necessary, prudent and rational.

    3. When we use antibiotics we must learn the most effective and

    efficient methods to administer them

  • My experience

    The majority of antibiotic use in aquaculture is imprudent,

    irrational, inefficient and not even economically justifiable

    This is a problem for not just aquaculture

    The majority of antibiotic use in human and veterinary

    medicine is also imprudent and irrational

  • Control of bacterial disease

    1. Prevent infections

    Limit the contact between the host and the pathogenic

    bacterium

    2. Increase the hosts resistance to infection

    Improve hosts general heath

    Vaccinate to limit specific infections

    3. Treat the infected hosts

    Antibiotics are a last resort

  • Antibiotics in the control of TB in UK

  • Prevention is better than cure

    When animals are dying the only option is (antibiotic) therapy

    But when animals are dying the factors that led to their

    disease have already happened

    It is too late to correct these factors

    But control of these factors is always the most efficient

    method of controlling disease

  • Deciding to apply antibiotic therapy is always a gamble

    Is the money that will be lost if no treatment is given

    greater than the cost of the therapy?

    The potential loss must always be a guess

    The direct cost can be quantified by individual farmers

    The long term indirect costs, associated with the

    selection for resistance, cannot.

    These long term costs will be borne by the wider industry, the

    wider community and ultimately everybody on the planet

  • Antibiotic therapy cannot

    1. Control industry-wide epizootics

    1. Compensate for poor husbandry

    1. Function as a growth promoter

    1. Have any effect on limiting losses associated with

    infections by resistant bacteria

  • Antibiotic therapy works best when

    1. The general health of the treated population is good and their

    environment suitable

    1. The target bacterium plays a major role in the disease process

    1. The dose is correct and its administration is efficient

    1. The antibiotic is administered in time

    1. The target bacterium is susceptible

  • Resistance and treatment

    To initiate a course of antibiotic treatment in the absence of any

    information on the susceptibility of the target bacterium is

    irresponsible

    imprudent

    and a potential waste of money

    We must design systems that allow health care professionals access

    to susceptibility data

  • The way forward

    Data requirements

    How much antibiotic are we using?

    How much resistance has resulted?

    Actions

    Provision of education in prudent use

    Provision of appropriate technical support

  • Thank you

    for your attention

  • What do we mean by resistant?

    Much confusion has resulted from our failure to agree

    exactly what “resistant” means

    A bacterium should be termed resistant only when its

    reduction in susceptibility is s

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