Antibiotic resistance

Antibiotic resistance, also known as antimicrobial resistance (AMR), is a global phenomenon affecting both public health and animal health. The HPRA is actively involved in helping address the issue, recognising the need for a multi-stakeholder approach across international and species borders to make a positive impact.

Understanding the issue: causes and concerns

Antibiotic resistance develops when bacteria are exposed to antibiotics. This is a complex issue, as resistance occurs naturally and can be transferred to various degrees under different situations. The World Health Organisation (WHO) provides more information on the causes of antimicrobial resistance. A particular focus is on safeguarding the usefulness of existing antimicrobial drugs classes, as only a few new chemical classes have been developed in recent years.

Impact of veterinary antibiotics

Using antibiotics in animals poses a potential risk, as it can lead to the selection and spread of resistant microorganisms both from animals to other animals, as well as from animals to humans. This risk arises from being in contact with treated animals or their surroundings and from consuming produce (such as milk, eggs, honey, meat) from treated animals. 

Many antibiotics used for animals are the same or from similar drug classes as those used for humans, albeit that approximately 88% of veterinary drugs used in Ireland come from older drug classes.  Antibiotics have been used widely in animals since the 1950s and are viewed by veterinary practitioners as being vital for treating animals suffering from infectious diseases.

Understanding resistance development

The development of resistance is a natural process which increases every time an antibiotic is used. While resistance emerges initially as a random occurrence during bacterial replication, it increases when antibiotics are used. Once resistance has occurred, further use of an antibiotic leads to selection pressure, as resistance genes are selected in the face of exposure to a particular antibiotic. The more often exposure occurs, the greater the risk. Bacteria multiply rapidly, so organisms with the resistant gene can rapidly become dominant in a bacterial population within an individual animal or human. 

These genes appear to confer some advantages to the bacteria concerned, as they can survive in the animal, human or the environment for a long period of time, even when the use of the antibiotic has ceased for weeks or even months.

Nowadays, exposure to even one antibiotic may result in the selection of resistance to a range of other antibiotics. The reason for this is that genes conferring resistance upon bacteria are often closely linked together.  During reproduction of the bacteria, these resistant genes link together and are transferred and replicated in the recipient bacteria. These genes, or DNA fragments, are available also to other bacteria that are present within the animal’s body or in the animal’s environment and may exchange genetic fragments with them.  

Some have likened this phenomenon to a type of ‘data cloud’, to and from which bacterial gene fragments are exchanged in a dynamic, opportunistic and promiscuous manner. Ultimately, these resistant genes are also available to bacteria which live in or on humans, which can lead to human infections in certain situations.

Mitigating resistance

The problem of resistance has increased over recent decades.

The risk of resistance increases if antibiotics are used:

• At too low a dosage.
• For too short a duration.
• Too often.
• As a blanket measure in an untargeted manner.
• For the treatment of bacteria that are not susceptible to the particular antibiotic.
• For the treatment of diseases caused by viruses or other germs not susceptible to antibiotics.
• For too long a period of time.

For the antibiotic to be effective in the treatment of a particular disease, the drug must be delivered to the diseased tissue at a concentration which is sufficient to kill or inhibit the bacteria causing the disease. It must be present for a long enough period to allow the animal’s immune system to mount a defence. Even then, the antibiotic being used will usually inflict collateral damage on other bacteria that it encounters, be they normal inhabitants of the gut, or in the environment. 

Antibiotics are powerful tools when used correctly. They are subject to prescription control in accordance with EU and national legislation. Moreover, veterinary practitioners are under ethical constraints in how antibiotics are prescribed and used.

Addressing the issue nationally and globally

In recent years the European Medicines Agency (EMA) has reviewed the indications and conditions under which a number of the more modern antibiotic classes (fluoroquinolones, macrolides and cephalosporins) are used in veterinary medicine. These reviews have resulted in the elaboration of more precise recommendations for use and new warnings which must be taken into account by vets when prescribing these antibiotics.

Separately, a number of organisations have developed ‘prudent use guidelines’ or ‘responsible use guidelines’. These documents are aimed at those using and suppling antibiotics and encourage the proper use of antibiotics.

HPRA advice on prescribing and using veterinary antimicrobials in dairy cows, ewes and goats

The HPRA is aware that residue standards for milk being operated by creameries for certain animal remedies might not always be exactly the same as those which have been set in the EU to protect public health. This issue applies primarily to antibacterial drugs given intramammarily as a means to control mastitis. The effect of this means that farmers supplying milk to creameries might need to observe additional precautions in order to ensure that they meet the creamery standards for milk delivery.

The residue benchmark used by the HPRA and other EU Member States to set withdrawal periods for animal remedies is the Maximum Residue Limit (MRL) established by the European Commission. These standards have been elaborated following a detailed scientific review of the toxicology of the drug as well as an analysis of the metabolism and elimination of the drug from treated animals. 

In respect of individual veterinary medicines authorised by the HPRA, studies are required that demonstrate the depletion of residues in treated animals to concentrations below those of the established MRL. These residue studies are used as the means to establish appropriate withdrawal periods for milk and meat of treated animals. Antibacterial screening tests used by creameries might not be calibrated precisely in line with the MRL or may be exquisitely sensitive for certain classes of antibacterial drugs (e.g. penicillins and cephalosporins) while being less sensitive to other drugs. 

The following precautionary measures apply to farmers and their health-care professions who are involved in supplying milk to creameries: 

1. Farmers should continue to be vigilant regarding the use of veterinary medicines and the avoidance of unwanted residues. 
2. Farmers should follow the directions of use stated on the product labeling and package leaflet unless directed otherwise by their veterinary practitioner. 
3. Creameries operating residue standards should clearly communicate those standards to farmers and their veterinary practitioners. 
4. An increase to the stated withdrawal period might be necessary where the creamery standard is more sensitive than the MRL established in the European Union.
5. Users of veterinary medicines should continue to report any suspected adverse reactions either to the company concerned (i.e. the marketing authorisation holder of the animal remedy concerned) or to the HPRA.

Use of antimicrobial drugs in Ireland

In Ireland, the Health and Safety Executive is responsible for gathering information on the consumption of antimicrobial drugs for human use annually, in accordance with a programme known as European Surveillance of Antimicrobial Consumption (ESAC).

Since 2009, the HPRA has gathered similar data nationally in respect of veterinary antimicrobial drugs, in accordance with a sister programme knows as European Surveillance of Veterinary Antimicrobial Consumption (ESVAC).

Annual HPRA reports

Reports on veterinary consumption of antimicrobial drugs for recent years can be downloaded.

ESVAC reports

The EMA gathers and collates information on the sales on veterinary antibiotics in the European Union. The latest information is available on the ESVAC webpage.

International initiatives

The EU network of medicines agencies, HMA, as well as the EMA and the EU Commission have developed strategic plans to address the issue (see links below). These plans seek to safeguard the availability of effective antimicrobials for use in animals whilst at the same time minimising risks to animals or humans.

CVMP

Visit the EMA's Strategy on antimicrobials document for more information.

HMA and EMA

Visit the European medicines agencies network strategy document (refer to page 20) for more information. 

European Commission

Visit the European Commission's A European One Health Action Plan against Antimicrobial Resistance document for more information.