Regulatory controls of antimicrobials
This chapter addresses the effectiveness of the implementation of the
JETACAR recommendations relating to regulatory control of antimicrobials. The
chapter summarises the Government response to the JETACAR report and a 2003
progress report on the implementation of the recommendations. The evidence
received by the committee regarding concerns about the implementation of
regulatory controls on the use of antimicrobials is covered, including use in
animals, use for growth promotion, off-label usage, and use in plant health.
Underlying the discussion and debate on regulatory controls is that
resistance levels are driven up by increased usage of antimicrobials. In
addition, as noted by Dr David Looke, reducing antimicrobial usage is one
of the most effective ways to bring resistance rates down:
[W]e need to somehow reduce the volume of antibiotics being
used, and that occurs across the human sector as well as the animal and
agriculture sectors. If you look at the one thing that has been proven to
reduce the move towards worsening resistance it is reducing the amount of
antibiotic pressure. So I think we need to try to do that across all areas.
What we would like to see is that antibiotics are only ever used when they are
Implementation of the JETACAR recommendations
JETACAR recommendations 1–9 focussed on the management of antibiotic
'load' and exposure in human and veterinary medicine through regulatory
controls over registration of antibiotics, imports and end-use regulations.
JETACAR stated that it was 'important that the regulatory processes for
antibiotics be identical or very similar for human and veterinary drugs and
that microbial resistance safety is formally assessed as part of the evaluation
of antibiotics for human as well as for animal use'.
The Government response
In its response, the Government indicated that it accepted or supported
six recommendations and began implementing or referring those recommendations.
The response also indicated that the Government accepted the intent of three recommendations
and offered qualified support, but took a different implementation path to that
specified by the JETACAR recommendations, as follows:
- recommendation 3 (licencing importers) – the Government accepted
the need for a stronger audit trail for importers to end users, but was not
convinced that licencing was appropriate and opted for a reporting and audit
- recommendation 5 (defining threshold/trigger rates of resistance
for antibiotics in animals) – the Government agreed with the intent of the
recommendation but opted for five yearly reporting of resistance data
associated with antibiotic use in animals, rather than putting resistance
prevalence information in product data; and
- recommendation 6 (all antibiotics for use in humans and animals
be S4 prescription only drugs) – the Government accepted the concept of
the recommendation, however, it indicated that there may be a need for
exemptions where the risk is low or acceptable. The need to take into account
existing industry codes of practice in implementing control of in-feed and
drinking water use of antibiotics was also noted.
Actions since JETACAR and current
In March 2003, the CIJIG released a progress report on the
implementation of JETACAR. In relation to regulatory controls, the progress
report noted that recommendations were being implemented, for example, the
three reviews of growth promotants suggested under recommendation 2 had been
initiated and activities were underway to improve national data on antibiotic
prescribing in response to recommendation 3. In relation to recommendation 6, consideration
of inclusion of antimicrobials for S4 scheduling was being undertaken.
DAFF stated that APVMA had fulfilled all of its obligations in relation
to the relevant regulatory control recommendations.
Actions included the completion of the review of virginiamycin and negotiation
with the Australian Veterinary Association for a code of practice on the
prudent use of antimicrobials.
In relation to human medicine, DoHA set out the key regulatory
mechanisms that are currently in place in Australia, which include:
- prohibition of the importation of antibiotic substances unless
permission has been granted by the Department, in accordance with Regulation 5A
of the Customs (Prohibited Imports) Regulations 1956;
- the scheduling of the majority of antibiotics as prescription
only medicines, which places controls on their supply and use where there is a
potential risk to public health and safety, including from resistant strains of
- that any product for which therapeutic claims are made must be
listed, registered or included in the Australian Register of Therapeutic Goods
(ARTG) before it can be supplied in Australia.
DoHA noted the recent accreditation change for hospitals which require
them to have antibiotic stewardship programs in place. The ACSQHC has
undertaken work on the implementation of Standard 3 of the National Safety and
Quality Health Service (NSQHS) Standards, "Preventing and Controlling Healthcare
Associated Infection". The standard aims to ensure appropriate prescribing
of antimicrobials by requiring the implementation of antimicrobial stewardship
programs to influence prescribing and use of antimicrobials.
The Government has also utilised the Pharmaceutical Benefits Scheme
(PBS) as a mechanism to ensure that the approvals for antibiotics subsidised
under this scheme encourage judicious and appropriate use. In addition, general
practices have been encouraged to achieve accreditation against the Royal
Australian College of General Practitioners (RACGP) standards for general
practices. The standards include a requirement that practices have systems in
place that minimise the risk of healthcare associated infections.
Industry groups provided information on regulatory controls in the
agricultural sector. The Veterinary Manufacturers and Distributors Association
noted that it had engaged with the APVMA and contributed to the management of
AMR issues associated with JETACAR initiatives.
The Animal Health Alliance informed the committee that:
The Alliance and its member companies have actively engaged
with government and federal regulators – particularly Australian Pesticides and
Veterinary Medicines Authority (APVMA) – in the regulatory activities initiated
out of the JETACAR report recommendations. The Alliance has always supported
risk based regulatory decisions made on the latest scientific information.
The ACMF emphasised to the committee that it does not support the use of
antibiotics for growth promotion in chickens. The ACMF supported the
classification of all antibacterial agents as prescription only.
In relation to JETACAR recommendation 3 – a stronger audit trail for
antibiotics from the importer to the end-user – industry now has record keeping
requirements embedded within assurance programs.
Australian Pork Limited (APL) also outlined the measures its industry has put
in place to manage antibiotics including that control of antibiotics on farms
is handled through herd health programs, supported by Standard Operating
Procedures and competent staff. The states and territories also regulate
competency requirements for staff. Additionally, relevant herds must also have an approved medications
list signed by a veterinarian that includes:
- descriptions of clinical signs of diseases and the medications to
- any in-feed medications used; and
dose rate to apply and if used as label or off-label.
Professor Cooper, also pointed to the success of self-regulation in
relation to use of third-generation cephalosporin antibiotics in chickens. Third
generation cephalosporin antibiotics are important antibiotics for human
medicine, as they are very broad in their activity and very safe to use.
Professor Cooper stated:
[I]ndustry should be applauded for selfregulation here; the
Australian Poultry Industry decided not to use a third-generation drug called
cephalosporin in chickens. As a result, the level of drug resistance in human
infections is 3% in Australia, compared to more than 50% in countries that use
The ALFA also informed the committee that antibiotics have been used by
livestock industries to treat sickness for over 50 years, noting that
resistance issues in human health were a more recent phenomenon. ALFA also
submitted to the committee that:
The use of antibiotics in the cattle feedlot industry is
extremely low with only 1-3% of cattle treated in any one year. This is because
antibiotics are overwhelmingly used only after infection is detected. i.e. as
per their use in human medicine. Notably, they are not used for growth promotion
Whilst the food safety regulator, Food Standards Australia
and New Zealand has determined that microbial loads are low in the red meat
supply chain, the cattle feedlot sector has introduced a number of best
management practices to reduce such loads further so that cattle health is
improved and the requirement for antibiotics reduced.
Concerns about the implementation of the recommendations
In contrast to the views of DAFF and DoHA, witnesses questioned the
effectiveness of regulatory arrangements to manage AMR in Australia. The
concerns covered issues relating to use of antimicrobials including use in
animals, use for growth promotion, off-label usage, use in plant health and
non-clinical use of metal based antimicrobials. In addition, the lack of a
cohesive and integrated approach was also raised in relation to regulatory
Overuse of antibiotics in Australia remains a challenge to manage,
despite recent progress, with NPS MedicineWise stating that 'every unnecessary
antibiotic prescribed contributes to resistance'.
Antibiotic stewardship aims to ensure that antibiotics are only prescribed when
they are required.
As stated above, ACSQHC has worked to implement standard 3 of NSQHS
Standards. As a consequence, all hospitals and healthcare facilities must have
a stewardship program in place in order to be accredited. Professor Baggoley,
commented that the NSQHS Standards are now mandated for over 1,500 hospitals
and health services. Professor Baggoley concluded:
I believe this approach gives us a very strong foundation in
moving forward with our efforts for the prevention and containment of
antimicrobial resistance in Australia and provides an excellent opportunity for
Australia to further expand and strengthen its response to this continually
evolving global health challenge.
The Royal Australasian College of Physicians also supported the
implementation of stewardship programs in hospitals.
Dr David Looke, commented that the adoption of standard 3 was a significant
However, the ASID also stated that 'the efficacy of this initiative in reducing
antimicrobial usage and consequently resistance is as yet unknown'.
Another submitter who sounded a note of caution was Associate Professor Gottlieb.
He noted the development of stewardship programs but voiced concern with the effectiveness
of their implementation:
I fear that the problem is that there is a lot of lip service
by administrations in hospitals regarding microbial stewardship. They see it
written down on paper as a mandated thing they have to do, but they find ways
of just looking like things are being done rather than committing funds to it,
because you do need to put funds into this.
Concerns about the implementation of Standard 3 and the issue of
incentives to encourage implementation are discussed in Chapter 6.
A further issue raised by submitters was that current stewardship
programs do not address prescribing of antibiotics by general practitioners.
Dr Looke commented:
One of the biggest challenges is going to be to move that out
into the community and into community practice, because most people get their
antibiotics prescribed by people who are private businessmen in their own
practices, and these are in general practice and specialist medical centres. Of
course, the types of stewardship programs that are being mandated through
accreditation have really no impact on that area.
Dr Looke went on to comment that the National Prescribing Service has committed
to an ongoing program addressing antibiotic prescribing. For example, in 2012
it focused on prescribing for respiratory infections.
NPS MedicineWise also submitted that there needs to be a consistent and
concerted effort to ensure practitioners better adhere to best practice
guidelines for these medicines.
Extension of antibiotic stewardship beyond healthcare institutions to
community care, long-term care facilities and non-medical antibiotic use was
recommended by the Antimicrobial Resistance Summit 2011.
Prescribing practices in the community are addressed further in Chapter
5 in the discussion on education.
Antibiotics usage in animals
JETACAR noted the benefits of antibiotic use in animals, including
economic benefits. However, the use of antibiotics in food-producing animals
can result in resistant bacteria in food-producing animals that can then cause
resistant infections in humans. It is also possible but yet to be established
that antibiotic residues coming through the food supply could increase
resistance when consumed.
JETACAR's recommendations included the review of the use of antibiotics as
growth promotants and prohibition of off-label use of veterinary chemicals
Dr Mark Shipp, DAFF, indicated that antimicrobials have a variety of
uses in agriculture and noted that they are used in animals under regulatory
controls to underpin animal health, animal production and animal welfare. The
health and productivity of farm animals are improved by the responsible use of
antimicrobial agents including antibiotics. The productivity of livestock
industries in Australia is important to ensuring a plentiful, affordable and
safe food supply. Antimicrobials are also essential in veterinary medicine for
While the importance of the use of antimicrobials for animal health,
production and welfare is recognised, the impact of antibiotic use in the food
chain on human health also needs to be considered. Professor Collignon stated
that 'there is good evidence that these resistant bacteria that develop in food
animals come through the food chain, are carried by people and then they cause
serious infections in people'. He pointed to the Netherlands where currently
between 25–50 per cent of the E. coli superbug (which is resistant to all third
generation cephalosporins) is causing serious disease including blood stream
infections in people and appears to be derived in large part from poultry sources.
In relation to the control of antibiotic usage in animals, submitters
pointed to the success in Australia of minimising resistance to
fluoroquinolone. Use of fluoroquinolone is banned for use in food animals in
Australia. Its use in human medicine is also restricted. It was noted that even
though Australians use large quantities of antibiotics, Australia has one of
lowest fluoroquinolone resistance rates in the world in humans as well as
almost no resistance in food animals.
Submitters argued that these examples pointed to the importance of the
implementation of the JETACAR recommendations relating to antibiotic use in
animals to minimise the development of resistant bacteria in humans. Submitters
considered that further regulation of antibiotic use in animals is required. Professor
Collignon, for example, commented that 'antibiotics are used in food animals in
ways that are not used in humans and that most physicians and people in the
community would regard as "abuse" of antibiotics and very poor
Professor Cooper added his view on the need to implement stricter
controls on the use of antibiotics in the food chain:
The Australian Dept. of Health and Ageing notes that
'Australia's food supply is one of the safest and cleanest in the world'. We
are lucky in Australia in that we enjoy access to a high standard of
healthcare. Whilst it is inhumane to withhold antibiotics for veterinary care
of sick animals, Australia needs to think carefully about our attitude to risk
and antibiotic use. With superbugs appearing more often in hospitals and
causing more deaths, what risks are we prepared to take with human health if we
continue to use antibiotics as growth promoters in animals?
Professor Grayson, also noted the need for better regulation in the
agricultural sector and commented:
I think for human use we have a pretty tight system—it can
always be improved—but in agriculture it is still not tight enough; it is not
defined. We have rules and we have regulations: 'You will do this or you won't
do that,' but they are not policed or checked. So there needs to be a
surveillance program about drug use in agriculture, as there is to some degree
The following discussion addresses significant matters raised in
relation to the use of antibiotics in the food chain: the use of antibiotics as
growth promotants; use in intensive farming; off-label use of antibiotics; and
use of 'critically important' antibiotics.
Antibiotic growth promotants
Antibiotics are used as growth promotants in food animals to destroy or
inhibit bacteria. They are administered at a low, sub therapeutic dose. The use
of antibiotics for growth promotion has arisen as more intensive farming
methods have been developed. Infectious agents reduce the yield of farmed food
animals and sub therapeutic doses of antibiotics are fed to animals to control
JETACAR noted that with advances in animal husbandry, genetics, disease
control and nutrition, antibiotic growth promotants are only one means of
improving productivity. JETACAR recommended that in-feed antibiotics should not
be used in food producing animals for growth promotant purposes unless they
meet certain requirements (recommendation 1). In addition, JETACAR recommended
the review of three classes of antibiotics used as growth promotants and that those
which failed the review process be phased out of use for this purpose. JETACAR
also recommended (Recommendation 13) the development of alternatives to
antibiotic growth promoters such as vaccination and improvements in feed
formulation and hygiene.
Professor Collignon was also of the view that the use of antibiotics as
growth promotants is now less important for growth promotion for animals than
antibiotic use for this purpose when discovered in the 1950s:
What is interesting is that after use of these antibiotics
for 50 years for that purpose in animals, if you look at the data now from big
poultry producers in the US, the Danish data that the WHO reviewed and others,
it shows that if you use routine antibiotics for either prevention or growth
promotion in animals reared under reasonable and good conditions it does not
make the animals grow faster.
Professor Barton commented that no new growth promotants have
been registered since JETACAR reported. However, a number of antibiotics
continue to be registered and used in the food producing industry as growth
promotants including some macrolides
such as kitasamycin and tylosin. In addition, most antimicrobial growth promotants are now
available as prescription only. However, Professor Barton went on to comment
that 'the use pattern is still that of growth promotant use i.e. used for
extensive periods of time or even the whole life of the animal' and that the use
of macrolides will facilitate the growth in resistance.
In addition there were concerns that the benefits of using antibiotics
in animals had not been evaluated in the context of the risks. Professor
A lot of the intensive farming practices, whether it is
chickens or pork, should be reassessed. We should ask: 'What is the
risk-benefit for that? If we manage them in a slightly different way, would we
If you look back through human health the key things that
improved our lives were not actually antibiotics; they were clean water,
appropriate housing and reduction of overcrowding. I think we have forgotten
those three rules when it comes to agriculture in the drive to try to produce
food at a slightly cheaper price. We need to ask people now, 'Would you rather
good quality food'—which most Australian food is—'and pay slightly more or
would you rather slightly cheaper but at a risk-benefit ratio?' At the moment
we do not know what that ratio is and I think we need to define it better.
Submitters supported the cessation of the use of antibiotics for growth
promotion. The Australian Veterinary Association, for example, stated:
Sub-therapeutic use of antimicrobials is a strong driver of
the emergence of antimicrobial resistant bacteria and antimicrobial growth
promotant use should cease as soon as practicable.
Professor Collignon noted that there has been wide-spread support for
the banning of antibiotic usage as growth promotants and some governments have
taken this action. However, some pharmaceutical companies have responded to
these moves by redefining the word 'therapeutic' so that this term now also
encompasses the routine use of antibiotics as prevention or prophylaxis. Professor
Collignon went on to state:
This is also often just continuing to use the same
antibiotics in the same doses as they were previously used when it was called "growth
promotion". I think this is an abuse of the term "therapeutic"
and is designed to just mislead governments, farmers and consumers. The JETACAR
report defined these terms and made it clear that if antibiotics were given in
the same way as "growth promoters" that that practice is
inappropriate and needs proper regulatory evaluation. Yet this
"prophylactic" practice seems to continue in Australia and
DAFF provided information on 'prophylactic use' and 'therapeutic use'
and stated that the boundary between the two is 'not always clear'.
Applications to change from use as a growth promotant 'would receive careful
scrutiny to ensure that it did not infringe on the policy set out in the
[JETACAR] recommendation' (recommendation 1). DAFF went on to comment that
an application of this type was 'unlikely'.
The Animal Health Alliance, which represents animal health product
manufacturers, stated that it has worked cooperatively with APVMA to deliver
improvements recommended by JETACAR including:
That the use of antibiotic growth promotants in
food-producing animals should not be used unless they:
- are of demonstrable efficacy in
livestock production under Australian farming conditions;
- are rarely or never used as
systemic therapeutic agents in humans and animals, or are not considered
critical therapy for human use; and
- are not likely to impair the
efficacy of any other prescribed therapeutic antibiotic or antibiotics for
animal or human infections through the development of resistant strains of
Industry groups also responded to concerns about the use of antibiotics
for growth in food animals. The ACMF, for example, commented:
While ACMF supports the use of evidence in decision making,
in recognition and appreciation of consumer concerns, the ACMF antibiotic
policy does not support the use of antibiotics for growth promotion of
APL stated that since JETACAR reported 'no evidence has emerged showing
that antibiotic effectiveness in humans has been undermined as a result of any
antibiotic prescribed in the pork industry'. The APL added:
Antibiotics are not used in the Australian pork industry for
growth promotant purposes. Antibiotics are only used for either prophylactic
use (to prevent a disease from occurring) or therapeutic use (to treat a
disease once it has occurred). For this reason, antibiotic usage in the
Australian pig herd is markedly less than many of our international trading
partners, including the USA, Japan, Spain and many other industrialised nations.
The APL went on to state that the aim of the industry is to minimise the
use of antibiotics through vaccines and better management of animals.
Professor Barton also commented on the steps taken by the pig industry:
The pig industry has clearly taken antimicrobial resistance
very seriously and the Pork CRC has a strategy to reduce antimicrobial use by
50% in 5 years. Unfortunately the other industries do not recognise a
problem and so antimicrobial resistance is a low priority or seen as a public
health issue that is not their responsibility.
In addition to growth promotion, other agricultural uses of antibiotics can
also drive the development of AMR. In particular, the preventative uses in
intensive farming were raised. Friends of the Earth Australia stated that
sub-therapeutic doses of antibiotics are used to maintain animal health of
livestock in the intensive farming sector. Friends of the Earth Australia argued
for a ban on non-therapeutic use of antibiotics in agriculture.
Professor Collignon also pointed to the changes in antibiotic usage in
Holland, where significant improvements have been seen, without adverse effects
in industry profitability:
Holland, for instance, has done that. Antibiotics are used in
people in the Netherlands at around the lowest rate in the world. It is half of
what we use in defined daily doses per person. But they perversely had the
highest use of antibiotics in the EU, so their vets were out of sync with human
medicine. ...What is interesting is that my understanding from hearing somebody
from there a couple of weeks ago is that they have decreased the volumes by 70
per cent without any evidence that this has hugely disadvantaged the animal
production sector in a global sense. Exactly the same happened in Denmark...There
has been a decrease overall of about 50 per cent in the total amount of
antibiotics used in that country, and they are still producing more pork; they
are still one of the biggest pork exporters in the world.
Some positive steps are being taken to find innovative ways to produce
food without using antibiotics, including other ways of preventing infections. Dr
Looke informed the committee that successful outcomes have been achieved in
aquaculture and the chicken industry:
I know from personally speaking to people that there is now a
lot of commitment in agriculture to try to work out how to do food production
without antibiotics. I note that there was some work done in aquaculture, with
trying to do prawn farming without adding antimicrobials, and it was quite
successful. There has been work in [the] chicken industry with breeding
different types of chicken stock that are resistant to the common infections
that spread through the high-intensity chicken breeding industries and they do
need to put antibiotics in the feed and the water for those types of things.
Dr Looke concluded that innovation and ways of preventing infections
should be promoted. This may mean research into vaccine development or ways of
preventing the common infections.
Alternatives to antibiotics in intensive farming are also discussed further in
Off-label use of antimicrobials
JETACAR recommended that off-label use of a veterinary chemical product
be made an offence. 'Off-label' use is defined in the JETACAR report as 'a use
practised by, or prescribed by, a registered veterinarian where the label
directions...are varied. For example, use on a different species...or by varying
the dose regime'.
The ASA noted that this recommendation was not implemented.
Currently, legal limits have been placed on the 'off-label' prescribing
of drugs by veterinarians under national control-of-use principles adopted by
most states and territories. These limits generally include:
- a ban on the use of unregistered products, to treat
food-producing animals, with the exception of single animals;
- a limitation on off-label use, prescribing or authorising for
food-producing animals of drugs and other veterinary chemicals unless they are
already registered in at least one major food producing species;
- a ban on use (or prescription/authorisation) contrary to any
instructions under a 'Restraint(s)' heading on a product label;
- a requirement to ensure all treated animals are adequately
identified, sufficient to last until the expiry of any relevant withholding
- a ban on formulating, dispensing or using a veterinary chemical,
registered for oral or external use, as an injection.
DAFF noted that there is no general APVMA risk assessment covering
off-label use of antibiotics in veterinary practice, as it is seldom possible
to foresee all off-label uses. The APVMA may decide, following its risk
assessment for an individual antibiotic product or a specific active constituent,
to impose conditions of use that may include controls on off-label use. Conditions
of use specified on a product label by the APVMA form part of the
state/territory control-of use regime. When the APVMA determines that off-label
use of a product should be restricted, specific label instructions are included
under a 'RESTRAINT' heading, for example: 'RESTRAINT: Not for use in food
producing animals'. Restraints are enforceable under state/territory
Professor Barton described the controls currently in place in the Australian
agricultural sector as 'very disappointing in that the lowest common
denominator approach was finally used to get all the States and Territories on
Professor Collignon also commented that the implementation of the recommendation
relating to off-label use as being 'very slow and poorly done'.
Significant gaps in the implementation of the recommendation were also
identified relating to restrictions on prescribing, prescribing for domestic animals
and dispensing by compounding pharmacies.
Professor Collignon also commented that since JETACAR, there have been
new developments such as the development of the World Health Organisation list
of 'critically important' antibiotics. Professor Collignon stated that community
based epidemics of fluoroquinolone resistant E. coli infections and Extended
Spectrum Betalactamase (EBSL) E. coli infections have occurred and that they are
clearly related in part to the use of certain 'critically important'
antibiotics in food animals especially in poultry.
Professors Barton and Collignon both pointed to the use of ceftiofur as
an example of poor implementation of the JETACAR recommendations. EAGAR had
recommended that a label restraint be put on ceftiofur, however, according to
Professor Collignon this recommendation was ignored by the APVMA.
Professor Barton stated that this 'critically important antimicrobial' is now
used in a wide range of animal species including pigs and poultry when it is
only registered very specifically for treatment of respiratory disease and foot
infections in cattle. It is also used for a wider range of conditions in cattle
The Australia Institute also noted Professor Collignon's comments in
relation to ceftiofur and stated that third generation cephalosporins such as
ceftiofur are currently used in food animals being registered for cattle use and
used off-label for pigs. Further:
Professor Peter Collignon from the Australian National
University has recently argued that he is not convinced by claims made by the
poultry and cattle farming sector that the use of ceftiofur is minimal. He
cites as reasons for his scepticism the lack of any rigorous surveillance and
monitoring of use and resistance, as well as the fact that advertisements in
trade magazines continue to promote inappropriate use of ceftiofur. A study in
2009 showed a quarter of Australian pig herds were given ceftiofur for treatment
Professor Cooper expressed concern that third-generation or
fourth-generation cephalosporins may be being used in veterinary medicine.
While Professor Cooper did not have any direct evidence that these antibiotics
are being used in animals, he argued that they should be taken off the schedule
of veterinary use because of their extreme value in human medicine.
The APVMA commented that the veterinary use of third generation
cephalosporins is 'severely restricted'. Ceftiofur is the only veterinary
medicine registered from this group and is available only on veterinary
prescription. APVMA stated that it must be used according to 'strict restraints'
including for individual animal treatment only.
However, Professor Barton noted that jurisdictions vary in what
veterinarians are allowed to prescribe with some allowing a wide discretion for
In some jurisdictions veterinarians can prescribe and
dispense whatever antimicrobials they like provided the use is not specifically
prohibited. Provided an antimicrobial is registered for use in one livestock
species in most situations vets can use that antimicrobial in all livestock
species, even if it is not registered for use in that species.
Professor Cooper also indicated that veterinarians are allowed by law to
'off-label' with veterinarians permitted to exercise professional judgement in
the off-label use or supply of most drugs or other veterinary medicines. He
noted that this gives veterinarians access to beneficial drugs which may be
registered for human use or which have limited registration for veterinary use.
Off-label use of antimicrobials in aquaculture was another issue raised
in evidence. In this case, evidence for the resistance to several important
antibiotics has been found. The Australian Institute commented:
[A]ssessment of the occurrence of resistance to
antimicrobials in bacteria from aquaculture species and environments in
Australia found resistance to a number of antimicrobials, including ampicillin,
amoxicillin, cephalexin and erythromycin, oxytetracycline, tetracycline,
nalidixic acid and sulphonamides. Multiple resistance was also observed.
These findings indicate that, even though no antibiotics are
registered for use in aquaculture, there has been significant off-label use.
This has potential implications for human health when fish are eaten and farm
run-offs contaminate the environment.
In relation to domestic animals, Professor Barton commented that antimicrobials
can be used off-label with no constraints at all in cats, dogs and horses.
A further concern raised by Professor Barton related to compounding
pharmacies. These have only emerged since JETACAR. The APVMA has no control
over them so that can legally formulate what they like, for example
fluoroquinolones, which are used in horses. Professor Barton went on to state that
that formulation is 'eminently suitable for use in other livestock species and
in aquaculture. It is clear that from time to time vets illegally dispense some
antimicrobials and the "free" availability from compounding
pharmacies makes illicit use much easier'.
DAFF indicated that proposed harmonisation of state and territory
veterinary prescribing and compounding rights is an element of the current COAG
reforms for a single national framework for the regulation of agricultural
chemicals and veterinary medicines. DAFF, in partnership with the states and
territories is developing models under this proposed framework for delivery to
COAG by the end of 2012.
Use of 'critically important'
The concept of critically important antibiotics has been established.
These critically important antibiotics provide a specific treatment, or one of
a limited number of treatments, for serious disease. Some antibiotics are
considered to be critically important for use in humans and others were
considered critical only for use in animals, and some are considered to be
critical for both humans and animals. The antibiotics considered critically
important for both humans and animals were considered to be priorities for
resistance surveillance and for implementation of appropriate management
measures to maintain the efficacy of the drugs.
DAFF provided the following information on the antibiotics used in
animals in Australia, including domestic pets, which are listed are 'critically
important in human medicine' by the WHO:
Table 4.1: Antibiotics on the WHO 'critically important in
human medicine' used in animals in Australia
Source: Senate Rural and
Regional Affairs and Transport Legislation Committee, Budget Estimates 2012–13,
Answer to question on notice No. 269, Department of Agriculture, Fisheries and
Professor Collignon commented that while fluoroquinolones have been
banned, much better regulation of drugs defined as 'critically important' for
human health by the WHO is required. He stated that:
In my view, we need to ensure that these drugs are not used in
food animals at all or if they are under much stricter controls than appear
currently to be the case. This is very important for poultry, as poultry seems
from international studies to be a disproportionate contributor to the carriage
of resistant bacteria by people compared to other foods.
Professor Grayson also commented that at the moment, Australia is not
adhering to the WHO critical antibiotic list. Although most are banned in
agriculture use, Professor Grayson stated that:
We are pretty good but we are not right there, and I think we
should be there. If we are going to achieve world-best practice we should be
adhering to a very thoroughly researched document like that and saying: 'The
drugs we're going to use in agriculture will be only those that are deemed to
The committee was also informed of the use of antibiotics in plant health
programs. In the USA about five per cent of antibiotics are used in plant
While a smaller part of the overall potential for causing resistance, it was
suggested to the committee that plant health applications should also be
considered for better regulation:
Bee antibiotic use and honey residues are areas which are
grey and not transparent. Plant Health Australia is responsible for bee health
policy due to the importance of bees to plant fertilisation, but the APVMA have
bees using veterinary medicines.
Other areas of concern relating to plant health, included ethanol
production and other fermentation processes. Goat Vet Consultancies pointed to
a lack of regulation for such activities:
Ethanol production industry overseas (and possible other
fermentation industries) also use antibiotics and such use is not regulated
either by APVMA as they do not register antibiotics used in manufacturing. In
Australia, the responsibility for regulating the use of antibiotics in
fermentation is uncertain as is the presence of antibiotic residue in fermentation
by-products that are used for livestock feed. Currently there are no national
standards for livestock feeds, although they have been in committee for a
couple of years.
The committee notes that in 2010, FSANZ undertook a risk assessment of imported
apples from New Zealand harvested from trees potentially treated with an
antimicrobial to control fire blight. It was concluded that there was negligible
increased risk to Australian consumers from potential exposure to AMR
Integration of regulatory
Submitters commented that effective and complementary regulation across
human medicine, veterinary medicine and the agricultural sector is required to
reduce indiscriminate use of antibiotics and to keep levels of AMR low in both
humans and animals.
While it was noted by Associate Professor Gottlieb that goodwill and interest
exists in reducing use of antibiotics, this was not enough: interest 'quickly
dissipates when they are faced with day-to-day realities and individual
patients, and antibiotics use often goes unchecked'. Associate Professor
Gottlieb went on to comment that not only is education required but also 'true
regulation of antibiotic use because goodwill and interest alone will not
He also added:
Ultimately, we feel that regulation is very important.
Antibiotics need to be restricted, how they are used needs to be better
controlled, and I fear that we particularly need to focus on non-medical use. I
do not have the evidence of how much use there is—that is not my area—but I see
some articles suggesting that it is substantial in other areas such as agriculture
and that we need to tightly regulate antibiotic use. There is so much evidence
about how much resistance is coming across the food chain and we cannot ignore
Submitters also called for the regulation of antibiotics in the human
and animal sectors to be brought together or, at least, that mechanisms be put
in place to ensure coordination.
Associate Professor Gottlieb commented:
...regulation of how antibiotics are approved and used should
be across human and other sectors. This could be done as one body. I cannot see
why antimicrobials should be split apart between different interested groups.
Dr Looke supported the creation of a central agency to coordinate drug
usage. In addition, a central agency could distribute information as new trial
evidence and new data becomes available. This would enable listings on the PBS
to be updated:
I think that all the agents that are used, right across, from
human and veterinary medicine to agricultural use, all need to be in the same
basket, so that we say: 'We have this drug. It is inappropriate to use this in
animal medicine because you have got this instead, which is a different group
of drugs, which we know, from evidence, does not promote resistance that can
come through the food chain into humans.' We need to have that sort of overview
of it. And then the PBS needs to reflect that.
Dr Looke also argued that the creation of central agency would overcome
the problem of relying on submissions by the original sponsor of a drug to
trigger a review. He pointed to the European approach where agents are only
licensed for a limited period of time. Once this has expired, new trial
information, new data and new indications are submitted. These submissions may
be made by people other than the original submitter.
In this regard, Dr Looke noted some approvals go back to the 1960s and
have never been reviewed by the TGA even though it may be of benefit to have
greater restrictions placed on the use of some antimicrobials. Dr Looke
Our whole formula of antibiotics were approved by the TGA,
often back in the 1960s, and have never been reviewed and gone through and
looked at again, simply because it is just too difficult, with the way the
current system is set up, to go back and redo things without sponsors wanting
to fund them. Of course, most antibiotics now are cheap drugs made by generic
companies that are not going to go and fund that type of relook when the answer
might be that the drugs should be more restricted in their use.
The Antimicrobial Resistance Summit held in 2011 made recommendations in
relation to regulation:
- resistance risk assessments should be part of the regulatory
process for bringing new antibiotics to market for both humans and animals.
- the Pharmaceutical Benefits Advisory Committee should consider
resistance in the criteria for inclusion or restriction of antibiotics on the
Pharmaceutical Benefits Scheme.
strategies should be implemented to enable 'fast-tracking' of
important new antimicrobials through the regulatory approval system.
strategies should be implemented to enable the registration of
'orphan' non-commercial drugs that have the potential to improve patient
outcomes and reduce disease burden.
adopting an antibiotic importance rating system as regulatory
policy should be considered.
The committee acknowledges that there are regulatory arrangements in
place that control the use of antimicrobials. In particular, the committee
notes the implementation of standard 3 of the NSQHS Standards which encourages
appropriate use of antimicrobials in healthcare services. Healthcare services
must have in place antimicrobial stewardship programs, monitor antimicrobial
usage and resistance, and act to improve antimicrobial stewardship. The
committee considers that this is an important step in reducing the overall use
of antibiotics in Australia.
However, the committee also received comments in evidence that stewardship
programs are not implemented thoroughly in certain circumstances. The committee
considers that consideration needs to be given to further reform and
coordination of use and access to antimicrobials in hospitals. In particular,
access to and use of any new antibiotics which become available should be
safeguarded for the future.
The committee recommends that the Australian Commission on Safety and
Quality in Health Care consider mechanisms to improve coordination and tighten
access to antimicrobials in healthcare services, particularly in relation to
any new antimicrobials that become available.
The committee considers it may be possible that more attention needs to
be paid to the prescribing practices of general practitioners. While much can
be done through targeted education programs (which are discussed in chapter 6),
the committee considers that other avenues should be explored to encourage
better antibiotic stewardship by general practitioners.
The committee recommends that the Department of Health and Ageing
investigate additional mechanisms to improve antibiotic stewardship in general
In relation to concern with current regulatory arrangements for animal
health, submitters were concerned that:
- Australia does not adhere fully to the WHO list of critically
important antibiotics that should not be used in animals;
- although no longer described as 'growth promotion', the same type
of antibiotic usage was thought to be occurring in food animals; and
- the emerging issue of the use of antimicrobials for plant health creates
another potential path for the spread of AMR.
The committee considers that Australia should strictly adhere to WHO list
of critically important antibiotics that should not be used in animals. This
would not only address a significant concern about the use of these drugs but
also enhance Australia's international leadership on AMR.
The committee recommends that consideration be given to banning all
antibiotics listed as 'critically important in human medicine' by the World
Health Organisation for use in animals in Australia.
The committee is particularly concerned about the weaknesses in the
current regulations relating to the off-label use of antimicrobials in animals
as well as the non-therapeutic use of antimicrobials in intensive agriculture
Off-label use of antibiotics may be wide-spread. Submitters noted that
JETACAR recommended that off-label use of antibiotics in animals be made an
offence. However, off-label use is allowed in certain circumstances under state
and territory legislation. Of particular concern was the use of
third-generation cephalosporins. The committee notes that proposals for the
harmonisation of state and territory prescribing and compounding rights is an
element of the Council of Australian Governments' reforms for a single national
framework for the regulation of agricultural chemicals and veterinary
There are moves overseas to ban the use of antibiotics as growth
promotants. The evidence received by the committee indicates that the benefits
of antibiotics as growth promotants is not as significant as it once was. Some
industry groups have indicated that this practice is no longer undertaken in
their industry. These industries are to be commended. However, it appears that
other industries continue to use antibiotics to improve growth in food animals.
The committee considers that appropriate cost-benefit analysis should be
undertaken to determine whether there are net benefits in allowing the practice
to continue, given the costs and disadvantages arising from AMR. The
cost-benefit analysis should be completed by a suitably independent body as an
input into revised regulations for non-therapeutic use of antimicrobials in
agriculture and aquaculture.
In addition, it was suggested to the committee that pharmaceutical
companies may be seeking to redefine the term 'therapeutic' to include the
routine use of antibiotics in disease prevention. While no evidence was
provided that this had occurred in a widespread fashion, the committee notes
that JETACAR considered that if antibiotics are given in the same way as growth
promoters, proper regulatory evaluation should be undertaken.
The committee did not receive any evidence on the extent to which
antibiotics are used for either prophylactic use (to prevent disease) or
therapeutic use (to treat disease once it has occurred). The committee
considers that more investigation of use of antibiotics for prophylactic use or
therapeutic use is required.
The lack of integration between the regulations relating to the use of
antimicrobials by humans and animals was a significant issue in this inquiry.
As Professor Grayson noted 'agriculture and human health are linked. The bugs
are the same. They do not care whether it is a cow or a human; it is just a
The committee considers that integrated regulations for AMR should also have a
particular focus on ensuring human and animal medicine are both addressed in a
consistent and complimentary fashion.
During the inquiry the committee also heard a range of other suggestions
for better regulation. The committee considers that the following points are
worthy of further consideration in developing an integrated AMR regulatory
- changing the arrangements for reviews of licences for antimicrobials
so that the license can be time-limited and reviews can be triggered by means
other than a submission by the original sponsor;
- requiring resistance risk assessments for bringing new
antibiotics to market for both humans and animals;
- enabling 'fast-tracking' of important new antimicrobials through
the regulatory approval system;
- enabling the registration of 'orphan' non-commercial drugs that
have the potential to improve patient outcomes and reduce disease burden;
- using antibiotic importance ratings; and
implementing resistance criteria for inclusion of antimicrobials
in the Pharmaceutical Benefits Scheme.
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