Antibiotic treatment - what's the (break)point?

Mink has been farmed for their valuable skins for many decades. This farming has been refined concerning animal welfare, health, and genetics in order to produce the most excellent skins. The wellbeing of the animals is closely connected to the quality of the skin.

The mink production follows a distinct seasonal pattern reflected in the annual natural reproduction cycle in the springtime of the animals, which means that all farmed mink in the northern hemisphere are following the same timeline every year in each production. This gives mink, as a study animal, several advantages as all mink are at the same stage of life at the same time. Advantages when investigating specific age-related diseases and when following a cohort of animals over a period of time.

Bacteria commonly identified in relation to diseases in mink include Staphylococcus delphini, Streptococcus canis, Streptococcus phocae, Arcanobacterium phocae, Escherichia coli, and Pseudomonas aeruginosa. Some are opportunistic commensals, e.g., S. delphini is a commensal of the skin and mucous membranes, which is often found in relation to pathological conditions in the skin and in relation to urinary tract diseases. Animals encountering a bacterial infection often require antibiotic treatment. However, there are no antibiotic guidelines and only one antibiotic registered for use in mink. This leaves the veterinarian with empirical therapeutic choices based on experience and dosages extrapolated from other animal species. Consequently, there is a great risk of overdosing and intoxication as well as underdosing and treatment failure, which in all cases ends up with unsuccessful use of antibiotic along with increased selection of resistant bacterial strains.

In this project, we aimed to assess the level of antibiotic resistance and antibiotic consumption in mink, with the objective to improve antibiotic therapy in mink. Data on antibiotic consumption and diagnostic results of clinical isolates were analyzed. A distinct pattern in antibiotic use reflecting age related problems in mink were discovered, along with minimum inhibitory concentrations (MICs) showing high resistance levels against the most commonly used antibiotics.

A library of clinical isolates of international origin from mink was tested against an extended range of antibiotic concentrations, in order to identify wildtype and non-wildtype populations and suggest tentative epidemiological cut-off values (TECOFFs). Genetic analysis showed that isolates with resistance genes also belonged to the phenotypical resistant non-wildtype populations. The TECOFFs are of high value as they may serve as surrogate of the lacking clinical breakpoints, and can be applied as pharmadynamic data in modelling of new dosage regimens.

The relationship between consumption and resistance was further investigated on farm-level in a cohort of mink during one production cycle. Significant associations were identified, especially regarding tetracycline, which was one of the most commonly used antibiotics.

Lastly, a novel pathogen, Streptococcus phocae, was identified and a careful investigation of the three unrelated diseased mink was undertaken. The mink presented with dermal infections and bacteremia, and the three isolates were genomic closely related. Along with the alarming high levels of resistance in clinical isolates, this identification of a new pathogenic bacterium in mink, highlights the importance of high-quality diagnostics.

In summary, this project provides novel information and findings in the field of antibiotic resistance and consumption in animal production. This information is vital for future optimization of antibiotic therapy in animal species encountering the investigated pathogenic bacteria. Additionally, the results of this study are of high value for the general understanding antibiotic consumption and resistance. In terms of One Health, it sheds light on the fact that all animals in close contact with humans should be part of national surveillance programs.