Abstract
Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed “green antibiotics,” having minimal ecological impact on the animal commensal and environmental microbiomes. We first explain why animal and human commensal microbiota comprise a “turnstile” exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic, and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem.
Highlights
The links between animals and humans, in respect of the emergence and spread of resistance, is a major global issue
This review proposes the development for veterinary medicine of new and innovative drugs for food-producing animals; this is not for animal health reasons but rather to mitigate the veterinary contribution to the human resistome
After gaining access to the human gastro intestinal tract (GIT) microbiota, these “Trojan horse” bacteria may transmit their resistance genes to the human commensal bacteria by horizontal transfer; these genes of resistance may be acquired by humanspecific pathogens (Angulo et al, 2004) or by opportunistic bacteria such as Enterococcus spp. responsible for nosocomial infections. To assess this collateral risk of antimicrobial drugs (AMD) use in veterinary medicine, antimicrobial resistance (AMR) in commensal bacteria is being monitored in indicator organisms of food-producing animals, E. coli for the Gram negative microbiota and Enterococcus (Enterococcus faecium and E. faecalis) for the Gram-positive commensal intestinal microbiota (European Food Safety Authority, 2013)
Summary
Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in foodproducing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes.
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