Resistance through a different prismEquine Vet J


A. E. Mather, D. J. Mellor, S. W. J. Reid


Resistance through a different prism

In the 100 years or so since the ‘discovery’ of antibiotics, the horse, like all our domestic species, has benefited from their use in the control of bacterial infections. Current debates on the use of antimicrobials in a veterinary context [1] are as relevant to the equine industry as to any other, both from a vested interest as well as from the vantage of the contribution to the pending ecological catastrophe that may see morbidity levels in man and animals returning to those of the 19th Century [2]. The issue is resistance.

Relative to the literatureon foodanimals, there is apaucityof information relating toantimicrobial resistance inequidaeand thatwhichexists focuses on treatment failure and upwards trends in prevalence. However, the material presented in recent articles [3–6] in the Equine Veterinary Journal goes some way to highlighting the several dimensions of antimicrobial resistance and the ‘one health’ nature of the problem; there are technical, behavioural and policy levels that must be addressed. Given the informed discussion that accompanied the papers, it is perhaps worthwhile setting the issues in a broader context and, in doing so, pose questions for which there are, as yet, few answers.

When considering the origins of antimicrobial resistance, we cannot escape the facts. First, antimicrobial resistance has been in the armamentarium of bacteria for over a billion years [7]; second, antimicrobial resistance can be found throughout our ecosystems, a ‘natural’ phenomenon, characterised as the resistome [8] and third, any use of antimicrobials can select for resistance [9]. Taken together, the implications are profound as it is clear that it is awarwe cannotwin and our best hope is to try to remain marginally ahead in the arms race with the bacterial pathogens we face.

As with other species, horses and other equidae play a role in this cycle of antimicrobial resistance, both within and between populations.

They carry resistant bacteria with zoonotic potential, including methicillin-resistant Staphylococcus aureus (MRSA) [10] and extended spectrum beta-lactamase producing Escherichia coli [11]. While direct contact may be the most obvious route of transmission between horses andman, even nonzoonotic bacteriamay act as a reservoir of antimicrobial resistance genes within the horse which can, once excreted into the environment, disseminate the resistance to other, potentially pathogenic, bacteria [12,13]. Aside from the public health aspects of antimicrobial resistance, this is an issue that also has an impact on horse health and welfare with economic consequences.

Hart et al. [4] describe a novel delivery system for antimicrobials. Given that the development of new antimicrobial drugs has stalled, besides ensuring that we continue to invest in research and development, we must also explore different ways of making the most effective and judicial use of the drugs we have. This novel application method for the local administration of antimicrobial drugs is by the use of a subcutaneous drug-impregnated dextran gel. They report that this delivery method ensures a sufficiently high concentration of drug is delivered to the target area, while largely avoiding spillover into the blood. This is important; nontarget microorganisms, which represent a reservoir of resistant organisms and resistance genes, are not exposed to the drug’s selective pressure. Also, given that a large proportion of many drugs are excreted from the body unaltered [14], these local application methods will limit the amount of antimicrobials finding their way into the environment, thus reducing their wider environmental impact. One might consider that this paper contributes to the technical or scientific aspects of a solution.

Barr et al. [5] report a different aspect of the judicious use of antimicrobials. Overwhelmingly, the commonly perceived benefits of the prudent use of antimicrobials are related to controlling or reducing antimicrobial resistance. In their study Barr et al. [5] address a challenge at the social and technical levels, increasing the awareness of other unintended consequences of antimicrobial use and second, investigating the prevalence and risk factors of antimicrobial-associated diarrhoea.

Although the prevalence of antimicrobial-associated diarrhoea was low, avoiding this potential clinical complication is of direct benefit to thepatient andmust be viewed as another reason for advocating prudent use of these drugs. It also opens up a debate on whether ‘prudent’ should be replaced by terms such as ‘appropriate’ or ‘targeted’ and where clinical context is a critical part of the decision-making process.

In a study of prescribing practices in the UK, Hughes et al. [6] address an issue that has elements at 3 levels: technical, behavioural and policy.

Without information on howmany andwhich antimicrobials are being used to treat horses and other equidae, we cannot begin to assess the extent of thepotential selectivepressureandhowthismight relate to resistance. The technical challenge is to determine the extent and nature of antimicrobial prescribing and assess how that may influence resistance; the social challenge is to understand why practitioners prescribe drugs as they do and the institutional challenge is how best to use that information to provide guidance to practitioners. Hughes et al. [6] set out to characterise the factors surrounding and reasons for antimicrobial prescribing in UK equine practices. The results are striking; the vast majority of practices treating horses had no antimicrobial use guidelines and the relatively high prevalence of off-licence prescriptions and inappropriate dosages have clear implications for the generation and dissemination of antimicrobial resistance. All these results suggest that the message on appropriate and prudent use of antimicrobials must be stronger. The issues highlighted in the last paper are, perhaps, the most concerning and serve as a call to action.