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

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 such that an

antibiotic therapy of its infections will fail