Why did my vet not prescribe an antibiotic?

Stuart Davies BVSc MRCVS, talks us through how antibiotics work and, why careful prescription is vital in reducing antimicrobial resistance

Since the discovery of penicillin by Alexander Fleming in 1928 antibiotics have been created and used for both humans and animals. Unfortunately, the emergence of antibiotic resistance has led to some classes becoming completely redundant in the treatment of certain pathogens or, within certain populations. While not all the blame can be put onto the veterinary world, certain misuse can’t be ignored. Blanket treatment of entire farm populations infeed irrespective of whether infection was present and, incorrect dosing had a large negative impact. Therefore, modern practitioners now aim to prescribe judiciously and cautiously to preserve the effectiveness of critically important antibiotics vital for human health. The absence of current or planned development of new antibiotics makes addressing this issue imperative.

How does resistance occur?

Several scenarios can increase the selection pressure for resistance within bacteria. However, it should be accepted that every time antibiotics ae prescribed, we are risking antibiotic resistance developing. There is therefore, careful consideration of every case, by your vet as to the need for antibiotics, to protect not only your horse’s but also your personal health.

“it should be accepted that EVERY time antibiotics are prescribed, we are risking antibiotic resistance developing“

Scenarios which do not usually require antibiotics include:

• Viral infection: these can be supportively managed using anti-inflammatories to control any associated pyrexia. While secondary bacterial infections can occur, antibiosis should not be given prophylactically.
• Foot abscess: the body has responded by walling off infection and once draining, resolves.
• Minor wounds: the immune system responds naturally by invoking inflammation (heat, swelling, discomfort). However, antibiotics may be required if infection develops or if the wound is associated with important structures.
• Strangles: although a bacterial infection, cases which are showing infection can have worse outcomes when antibiotics are administered. The formation and ons
• equent eruption of an abscess represents the body’s natural defence mechanism. These cases should be managed supportively with anti-inflammatories and nursing care.
• Diarrhoea: this can have many causes in the horse and is rarely associated with bacteria. In fact, antibiotics can have damaging effects on the ‘helpful’ bacteria within the horse’s gut causing more issues.

How do antibiotics work?

Antibiotic drugs are divided into different classes depending upon their chemical structure. Between these classes the mode of action of the antibiotic may also differ. For example, penicillin belongs to the beta lactam family and works by preventing the bacterial cell wall from forming. Whereas sulphonamides inhibit the production of folic acid by competing with PABA ( para-aminobenzoic acid) to bind to a bacterial enzyme. Therefore, bacterial growth is inhibited.

Being aware of the method of action of the antibiotic is important to prescribe the correct antibiotic for the disease presented. For example, sulphonamides should not be prescribed when pus is present. In pus and necrotic tissue there are high concentrations of PABA. Therefore, there is a greater binding of PABA to the bacterial enzyme than the antibiotic can compete with, rendering the antibiotic ineffective. In addition, the way in which bacteria become resistant to different antibiotic relates to the classes chemical structure and the mechanism of action¹.

The acquisition of resistance by bacteria is a natural evolutionary change which is accelerated by improper use of antimicrobials. There are five main mechanisms of antimicrobial resistance. These include:

Enzymatic inhibition: This is the most common mechanisms of enzymatic resistance. Gram negative bacteria can release β- lactamase enzymes, which can hydrolyse β- lactams and cephalosporin antibiotics impairing their function.
PBP modifications: These important proteins are involved in the production of peptidoglycan for the bacterial cell wall. Modifying these PBPs changes the target upon cell walls that drugs recognise reducing their affinity.
Porin modifications: Porins are within the outer cell wall of gram-negative bacteria. Changes to the size, shape and structure of these can reduce the transport of drugs into the bacterial cells.
Efflux pumps: Bacteria can manufacture efflux pumps to actively remove bacteria from within the bacterial cells.

Changes to the drug target

Multi-drug resistant (MDR) bacteria are increasing in prevalence. These represent a particular challenge as they are resistant to at least 3 antibiotic classes. There are several bacteria of particular concern including Staphylococcus aureus, enterobacteria such as Salmonella and Enterococcus in addition to Pseudomonas. For normal healthy individuals contact with these pathogens may result in voidance of the bacteria or subclinical infection. However, these individuals represent a significant biosecurity risk as pathogens can be shed for numerous weeks without any external signs. For unhealthy individuals, which will be those of particular veterinary concern, these bacteria can be associated with a variety of infections. While some infections can be mild those involving wounds and systemic infections such as pleuropneumonia, sepsis and colic can be fatal¹. Moreover, these bacteria have been demonstrated to be passed from horse to human, deemed zoonotic, and pose a significant risk to human health³. Therefore, whether handling a horse in a veterinary setting or day-to-day, thorough hand washing and good hygiene is vital.

The problem with antimicrobial resistance is that it can be transferred between bacteria. This doesn’t just happen when the bacteria replicates but also across to bacteria with a separate origin, this is horizontal gene transmission. Genes responsible for antimicrobial resistance are contained within bacterial DNA and plasmids. Plasmids are small circular segments of bacterial DNA which can be transferred between bacterial cells via conjugation. Other bacteria can take up these small segments of free DNA following breakdown of bacteria by inflammatory cells, termed transformation. Bacteriophages, viruses that infect bacteria, are responsible for transduction. Packages of DNA are released in virus particles for uptake by other bacterial cells².

The most vital classes required for human health are restricted for use within the veterinary field. The classes identified by the World Health Organisation as being protected are Fluoroquinolones, 3rd & 4th generation cephalosporins, glycopeptides and macrolides. These antibiotics are only to be used if no other antibiotic is suitable for use following culture and sensitivity results⁴. Unfortunately in equine veterinary medicine, we are limited with the antimicrobials that are licensed for use. This is the process of testing an antibiotic in order to prove it’s use for a certain pathogen, at a certain dose and via a certain method of administration. Over time studies have shown that since the initial licensing these antibiotics work on the same bacteria in a different disease, a different bacterium altogether and therefore you may find that your vet is treating a different condition than the one recommended on the drug label. Additionally, to add further complication a better antimicrobial effect may have been demonstrated with an altered dose or frequency of administration, so that may also be different. It is important to follow the dose and frequency of administration on the prescription label that your vet provides to ensure effectiveness of the antibiotic. We should always aim to prescribe an equine licensed product when possible and only go to protected antimicrobials when there is a culture and sensitivity report to indicate resistance to all other available antibiotics⁵.

References

1. Knych, H. K. and Magdesian, K. G. (2021) ‘Equine antimicrobial therapy: Current and past issues facing practitioners’, Journal of veterinary pharmacology and therapeutics, 44(2), pp. 270–279

2. de Sousa Oliveira, K. et al. (2016) ‘Mechanisms of Antibacterial Resistance: Shedding Some Light on These Obscure Processes’ Elsevier Inc.

3. Schwaber, M., J. et al (2013) ‘Clonal Transmission of a Rare Methicillin- Resistant Staphylococcus Aureus Genotype Between Horses and Staff at a Veterinary Teaching Hospital’. Veterinary Microbiology. 162 pp 907-911

4. Dunkel, B. (2021) ‘Responsible antimicrobial use in critically ill adult horses’, Equine Veterinary Education, 33(12), p. 653.

5. Rule, E. K., Boyle, A. G. and Redding, L. E. (2021) ‘Antimicrobial prescribing patterns in equine ambulatory practice’, Preventive veterinary medicine, 193, p. 105