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Antimicrobial resistance and antimicrobial stewardship

By Dr Peter Evans, SAPPO’s health liaison officer
Definitions
Antimicrobial

An antimicrobial is a drug that selectively destroys or inhibits the growth of microorganisms. Sometimes referred to as an “antimicrobial agent”. Examples include antibiotics (also known as antibacterials) antiviral and antifungal agents.
Antimicrobial resistance (AMR)
The ability of a microorganism to grow or survive in the presence of an antimicrobial at a concentration that is usually sufficient to inhibit or kill microorganisms of the same species and that exceeds concentrations achievable in the human/animal/patient.
Antimicrobial stewardship
The use of co-ordinated interventions to improve and measure the use of antimicrobials by promoting optimal drug regimen, dose, duration and route. The aim is for an optimal clinical outcome and to limit selection of resistant strains. This is a key component of a multi-faceted approach to preventing antimicrobial resistance.
Antibiotics
Term derived from Greek word “anti” = against and “bio” = life. Louis Pasteur & Robert Koch were first to note antibiotic effect in 19th century. Sir Alex Fleming discovered penicillin in 1928, this was followed in 1932 by a Sulphonamide in the Bayer lab. In 1939 Rene Dubos discovered tyrothricin, which due to its toxicity, was used exclusively for wound treatments.
In 1942 Ernst Chain and Sir Howard Florey purified enough Penicillin G to treat a patient.
Initially the term antibiotic was used for naturally derived products, but has since been used to include all antimicrobials, both synthetic & natural, that “kill” bacteria.
Minimal inhibitory concentration (MIC)

The lowest concentration of an antibiotic that, under a certain set of experimental conditions, inhibits visible growth of a bacterial culture.
Minimum bactericidal concentration (MBC)

The lowest concentration of an antibiotic that, under a certain set of experimental conditions, kills a bacterial culture. MIC & MBC are basically identical for bactericidal drugs but can be vastly different for bacteriostatic drugs.
Antimicrobial resistance
Antimicrobials have been widely used in both human and animals for the past 80 years to treat many different types of infections. Due to the effectiveness of these products one could argue that many poor hygiene practices on human side have emerged in hospitals; and on animal side one was able to “get away with” lower biosecurity and disease management practices.
To understand why AMR develops it is necessary to briefly describe how antibiotics work.
Some antibiotics inhibit bacterial growth andreplication – these are known as bacteriostatic (an example is Tetracycline). A vigorous immune system is necessary for bacterial infection to be eliminated if one is using this type of antibiotic. Some antibiotics are bacteriostatic at low doses, but become bactericidal (kill bacteria directly) at higher doses e.g. florenfenicol, tiamulin, pleuromutilin
Examples of bactericidal antibiotics are penicillin, cephalosporins, floroquinolones and aminoglycosides. A further consideration in deciding how to use these antibiotics is whether they are concentration dependent bactericidal antibiotics – i.e. the dose needs to be correct or whether they are time dependent i.e. need to be used for correct length of time.
In deciding which antibiotic to use it is also necessary to understand the pharmacodynamics of antimicrobials. Treating a respiratory infection with a drug that does not accumulate in the lungs for instance would be futile. Just as futile would be treating Gram negative bacteria with antimicrobial drugs that are effective only against Gram positive bacteria.
Development of AMR is a fact of life and an ongoing debate as to the source of the AMR rages on. In the UK Five Year AMR Strategy (2013), they state “Increasing scientific evidence suggests that the clinical issues with AMR that we face in human medicine are primarily the result of antibiotic use in people, rather than the use of antibiotics in animals”.
Whether or not AMR’s are transferred to humans or not via meat or other means should not detract from veterinary and agricultures efforts to improve antimicrobial stewardship. Cases of AMR to some common infections (e.g. colibacillosis) on farms are identified fairly regularly.
In an article by Dan Andersson and Diarmaid Hughes (Nature Reviews Microbiology, 27 May 2014), they suggest that at below MIC levels a selection process for AMR increases as well as possibility of generating (causing) AMR’s to develop.
This article highlights the dangers of using antimicrobials for growth promotion where most times drugs are well below MIC.
Strategy
As a user of antibiotics the first step for the pig industry (and other food producing animal industryies) is to get our own house in order:
SA has two Acts which regulate the use of medicines in animals: – Act 101 Medicines Control managed by dept. of health, and Act 36 Livestock Remedies managed by DAFF.
Most antibiotics used on farm are registered under Act 101, as schedule 4 drugs. This means that users of these drugs need to have valid scripts in exactly the same way as required by pharmacists to dispense antibiotics to humans.
Despite this legal requirement too many cases of antibiotics landing up on farms without proper scripting is rife. These incidences could easily result in access to antibiotics for farm use being curtailed.
It is incumbent on both the veterinarian and the user (farmer) to use drugs judiciously; the former, to make correct diagnosis and prescribe the correct antibiotic and the latter to use drugs as prescribed. The choice of antimicrobial is complex and can only be done by the veterinarian.
The trend globally in managing AMR’s is to reserve some drugs known as Critically Important Antibiotics (CIA’s) for use in humans. There is no justification any longer for using antimicrobials for growth promotion, they should only be used therapeutically (i.e. to treat bacterial infections).
Many organisations including the Pig Veterinary Society in South Africa are compiling guidelines for prudent use of Antimicrobials.
The pig industry has a proud record of being a leader amongst food producing animal industries; examples include developing a Quality Assurance program, compartmentalisation improved farming methods, high health herds. Antimicrobial Stewardship must be added to the list.

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