Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic, and is a specific type of drug resistance (Alliance for the Prudent Use of Antibiotics (APUA), 2014). Antibiotic resistance evolves naturally via natural selection through random mutation, but it could also be engineered by applying an evolutionary stress on a population through poor infection control, global trade and through the misuse of antimicrobials (APUA, 2014). Antibiotic resistance is a natural phenomenon. When an antibiotic is used, bacteria that can resist that antibiotic have a greater chance of survival than those that are ‘susceptible’. Susceptible bacteria are killed or inhibited by an antibiotic, resulting in a selective pressure for the survival of resistant strains of bacteria (Figure 1 and 2) (APUA, 2014).
Antibiotic resistance in bacteria spreads at three levels:
- By transfer of bacteria between people and or animals
- By transfer of resistance genes between bacteria (usually via plasmids)
- By transfer of resistance genes between genetic elements within bacteria, on transposons. A transposon (or transposable element) is a small piece of DNA that inserts itself into another place in the genome.
Understanding the mechanisms involved in resistance to antibiotics is of importance both for the responsible use of antibiotics in practice, and for the development of new antibacterial drugs to circumvent resistance (Rang et al, 2003).
Developing new antibiotics
The first antibiotic penicillin was discovered by Alexander Fleming in 1928 (Fleming, 1929), and more than 100 compounds have been found since, but no new class has been found since 1987 (Ling et al, 2015). One of the difficulties with developing new antibiotics is that the majority of microbes (99%) will not grow in laboratory conditions (Ling et al, 2015). The microbes within soil do produce chemicals that ward off other microbes, and it is these chemicals that researchers are investigating as potential new antibiotics.
The Antimicrobial Discovery Centre at Northeastern University in Boston, USA announced in January 2015 that the research group had developed a novel innovative device called an iChip that cultures bacteria in their natural habitat (in the soil). The device sandwiches the bugs between two permeable sheets. It is then pushed back into the ground where the microbes grow into colonies. By using this new technique researchers have been able to grow the microbes which produce naturally occurring antibiotics that fight off other microbes in the same habitat. One compound, so far, has been discovered, teixobactin, which is highly effective against common bacterial infections Clostridium difficile, Mycobacterium tuberculous and Staphylococcus aureus (Ling et al, 2015).
Critically important antibiotics (CIA)
There are three key groups of antibiotics; fluoroquinolones, 3rd and 4th generation cephalosporins and macrolides have been classified as CIAs for human health by the World Health Organisation (WHO, 2015). They are also classified as veterinary critically important by the World Organisation for Animal Health (OIE). There are situations where the bacteria causing disease are resistant to other groups of antibiotics, and a veterinary surgeon may need to prescribe a CIA to ensure that an animal is treated effectively. Less than 15% of the antibiotics sold for veterinary use in the UK in 2011 were those identified by the WHO as critically important for human medicine. The UK position on the use of CIAs by the veterinary sector remains that these antibiotics should be reserved for clinical conditions that respond poorly to other classes of antibiotics, and where antibiotic sensitivity testing has been carried out (BSAVA, 2014). Discussions with clients on the importance of using the correct antibiotic in order to treat their animal is vital. There is always a cost implication in these matters, but the cost of one culture and sensitivity test, could potentially be less than a course of the incorrect antibiotics.
Biosecurity
There is great importance in veterinary practice that preventative measures of biosecurity are in place in order to reduce the initial use of antibiotics. Veterinary nurses (VNs) are well placed to play a vital role in biosecurity; VNs can be given responsibility for the biosecurity procedures within veterinary practices. Biosecurity protocols are required under the Royal College of Veterinary Surgeons (RCVS) Practice Standards Scheme (PSS) (RCVS, 2015) and attendance at a CPD event on biosecurity should be included. Any knowledge obtained at a CPD event should be disseminated throughout the practice, and evidence of this occurring should be documented.
The importance of infection control procedures should not be underestimated. Cleaning protocols for all areas of the practice need to be set out, alongside cleaning schedules. Additional guidance needs to be in place for infectious and zoonotic diseases.
Differences in dilution rates for cleaning products need to be adhered to, and correctly measured out. All organic material should be removed prior to the disinfection of floors and surfaces. It is also recommended that all fomites (mop, mop bucket, brooms) are regularly cleaned and disinfected (Box 1). It is possible for bacteria to develop resistance to disinfectants via the same mechanisms as with antibiotic resistance. Correct dilution rates are therefore equally important as antibiotic dose rates in order to prevent a selective pressure for resistance. It is vital to follow the manufacturer's guidelines, dilution rates and the contact time of the fluids to the surface.
Box 1.Methods of increasing biosecurity in veterinary practiceIncreasing biosecurity in practice:
- Hand washing, alcohol gels (clients and staff) should be placed strategically around the practice
- Uniforms only to be worn within the practice, changing into your uniform when reaching work
- Ensure that all fomites are cleaned regularly (mops, buckets, brooms)
- Veterinary vehicles that go onto farms need to be kept clean. Especially when going from farm to farm
- Effective barrier nursing techniques should be applied for infectious cases
Prevention of the use of antibiotics
In order to reduce antibiotic resistance, the first step is to reduce their use, therefore reducing the likelihood of resistance from occurring. There are many ways in which the use of antibiotics can be reduced and these include:
- Vaccination, it should become the norm that all dogs are vaccinated against all preventable diseases such as kennel cough. Annual outbreaks of the disease can be avoided if there is good ‘herd’ coverage
- Keeping the animal healthy, with good nutrition and husbandry. Reduction of flies, for example, may reduce the incidence of summer mastitis; bacterial causes include Arcanobacterium pyogenes, Peptostreptococcus indolicus, Streptococcus dysgalactiae which act synergistically, and transmission of infection is thought to be by the head fly (Hydrotea irritans) (NADIS, 2015). Good nutrition aids in keeping the animal healthy with a good immune response
- Quarantine protocols, for all animals entering into the environment (farm, kennels).
Reduce and refine
Public Health England released figures in October 2014 looking at antibiotic usage in human medicine (Public Health England, 2014):
- There was a 6% increase in prescriptions between 2010 and 2013
- A rise from 25.9 to 27.4 doses per 1000 people per day
- Doctors in Merseyside are prescribing 30.4 defined daily doses per 1000 people compared with just 22.8 in the Thames Valley region
- There was a link between areas of high prescribing and resistant bacteria in that area
- There was 12% increase in the number of resistant Escherichia coli infections in the blood.
These figures proved to be quite disappointing to Public Health England who thought that numbers were reducing, especially as there has been a drive to reduce use of antibiotics within the National Health Service in the UK.
One recommendation made by the Veterinary Medicines Directorate is that antimicrobial use as a prophylactic is reduced/removed within veterinary medicine. This has already occurred in some EU members countries, such as Denmark. The definition of prophylaxis and metaphylaxis are different in the two industries (veterinary and human medicine), and the veterinary industry needs to be looking at reserving the use of antibiotics for curative and control treatment:
- Curative treatment (also referred to as therapy) — treatment of a sick animal or group of animals following the diagnosis of infection and/or clinical disease.
- Control treatment (sometimes referred to in veterinary medicine as metaphylaxis) which is mostly equivalent in human medicine to prophylaxis — treatment of a group of animals after the diagnosis of infection and/or clinical disease in part of the group, with the aim of preventing the spread of infectious disease to animals in close contact and at considerable risk and which may already be (sub-clinically) infected. A useful comparison with human medicines would be where a child in a classroom is diagnosed with meningococcal meningitis necessitating urgent treatment of all other in-contact children.
- Preventive treatment (sometimes referred to as prophylaxis) — Treatment of an animal or a group of animals, before clinical signs of infectious disease, in order to prevent the occurrence of disease or infection.
It is vital that the correct antibiotic is used (refine), the use of broad spectrum antibiotics for all uses is not advocated (British Small Animal Veterinary Association, 2014). Selection of the antibacterial needs to be made through culturing and sensitisation of the bacterial growth. Specificity is key in the reduction of resistance from occurring.
Compliance
The act of compliance is important in preventing resistance. There are many areas/strategies that can be utilised/implemented to aid in compliance including the use of posters in waiting rooms, smart phone apps to remind clients to tablet their pet, and videos being available online on how to medicate animals. The palatability of medications and their size are vital in aiding in the administration of medication. In the autgor's experience new innovative methods of administration really do help clients with compliance. It is important for the veterinary surgeon to discuss with clients formulations of medications that they can easily administer.
Monitoring resistance
Within the UK any lack of efficacy of medications of any type need to be reported to the Veterinary Medicines Directorate (VMD) under pharmacovigilance. This includes resistance to antibiotics, anthelmintic and lack of efficacy to vaccines. Reporting of lack of efficacy needs to be completed through the VMD website (www.vmd.defra.gov.uk/adversereactionreporting), figures are collated for the UK Veterinary Antibiotic Resistance and Sales Surveillance UKVARSS report (VMD, 2014).
BSAVA PROTECT
The British Small Animal Veterinary Association (BSAVA) have developed the PROTECT policy, in order to reduce antibiotic resistance. The acronym PROTECT stands for:
- Practice policy?
- Reduce prophylactic use
- Other options for treatment?
- Types of drugs and bacteria?
- Employing the correct antibacterial?
- Cytology and culture
- Treating effectively.
Each of these elements should be utilised in order to aid in resistance. PROTECT posters can be utilised in order to offer guidance in the correct use of antibiotics for specific indications. The website is a valuable resource for all staff in the veterinary profession, www.BSAVA.com./resources/PROTECT.
Client education
Education of pet owners and farmers is vital in the reduction of antibiotic resistance. Veterinary surgeons need to be discussing with owners why a culture of the infection is advantageous rather than just prescribing another course of antibiotics. Owners need guidance on compliance, and why it is important in AMR. Veterinary nurses are still being underutilised in this role, and owners should be given the opportunity to discuss methods of medicating pets, husbandry and nutrition with veterinary nurses. Client literature on antibiotic use, administration methods and infection control can be ideally utilised in practice, alongside posters in reception areas. Initiatives like Antibiotic Guardian (www.antibioticguardian) are an excellent way in which veterinary nurses can engage professionals and the general public.
Conclusion
There is a strong possibility that there will be tighter controls surrounding the prescribing and use of antibiotics in all sectors of medicine (human and veterinary). Everyone in all of the professions needs to be on board with the recommendation made by various human and veterinary associations with respect to antibiotic use, in order to safeguard their continued usage in veterinary medicine, as animal welfare issues will increase.
Key Points
- Infection control is paramount in aiding in reducing the risk of antibiotic resistance.
- Owner education in why compliance with specific veterinary instructions is important in order to prevent antibiotic resistance.
- Preventative measures, such as vaccination, good husbandry, infection control, can all aid in reducing antimicrobial resistance.
- Antibiotic protocols should be in place within the veterinary practice to ensure appropriate use of these medications.
- Responsible use of antibiotics will help to preserve their use for the future.