Comparing human and animal antimicrobial usage: a critical appraisal of the indicators used is needed.

Comparisons between antimicrobial usage (AMU) in humans and food-producing animals are regularly made. The accuracy of such comparisons depends on the indicators used to quantify AMU. Indicators for AMU quantitatively relate use data (the numerator) to population data (the denominator). The denominator should be a proxy for the population at risk in a certain period when comparing the exposure of different populations to antimicrobials. Denominators based on numbers of animals slaughtered, such as the commonly used population correction unit, do not consider the time at risk of antimicrobial treatment. Production-based indicators underestimate animal AMU. Additionally, production-based indicators are fundamentally different from indicators used to quantify human AMU. Using such indicators to compare human and animal AMU therefore leads to biased results. More caution should be taken in selecting the indicator to quantify AMU when comparing AMU in food-producing animals and humans.

Colistin Use in European Livestock: Veterinary Field Data on Trends and Perspectives for Further Reduction.

Polymyxin E (colistin) is a medically important active substance both in human and veterinary medicine. Colistin has been used in veterinary medicine since the 1950s. Due to the discovery of the plasmid-borne mcr gene in 2015 and the simultaneously increased importance in human medicine as a last-resort antibiotic, the use of colistin for animals was scrutinised. Though veterinary colistin sales dropped by 76.5% between 2011 to 2020, few studies evaluated real-world data on the use patterns of colistin in different European countries and sectors. A survey among veterinarians revealed that 51.9% did not use or ceased colistin, 33.4% decreased their use, 10.4% stabilised their use, and 2.7% increased use. The most important indications for colistin use were gastrointestinal diseases in pigs followed by septicaemia in poultry. A total of 106 (16.0%) responding veterinarians reported governmental/industry restrictions regarding colistin use, most commonly mentioning "use only after susceptibility testing" (57%). In brief, colistin was perceived as an essential last-resort antibiotic in veterinary medicine for E. coli infections in pigs and poultry, where there is no alternative legal, safe, and efficacious antimicrobial available. To further reduce the need for colistin, synergistic preventive measures, including improved biosecurity, husbandry, and vaccinations, must be employed.

Real-World Data on Antibiotic Group Treatment in European Livestock: Drivers, Conditions, and Alternatives.

Major efforts have been made by veterinary professionals to reduce the need for antibiotic use in animals. An online survey launched by the Federation of Veterinarians of Europe (FVE) aimed to gather responses from practicing veterinarians with field experience in metaphylactic livestock group treatment. Only 17% of all veterinarians (n = 183/1087, all species-specific responses merged) applied metaphylactic group treatments to 75% or more of all their treatments. Significantly less metaphylactic group treatments were reported in mixed practices (p = 0.002) and practices specialized in cattle (p < 0.001) as well as small (p = 0.007) and very small practices (p = 0.009). Gram-negative bacteria, mostly composed of Enterobacteriaceae and Pasteurellaceae, were considered by 75.3% (n = 967/1385) as the most devastating bacterial pathogens. Respondents alleged morbidity (20.1%, n = 201/998) and mortality (42.2%, n = 421/998) as major consequences for animal health and welfare if metaphylaxis would be banned. Responding veterinarians pointed towards vaccinations; improved biosecurity, including hygiene measures; and improved herd health management as the three most effective alternative measures to prevent metaphylactic treatment. However, more research is needed on how to implement appropriate alternatives in a holistic hurdle approach. Active support on a national level will be necessary for the development and application of targeted veterinary treatment guidelines for practitioners, which promote the understanding of drivers and include initiation criteria for metaphylactic group treatments in livestock.

Review and Analysis of National Monitoring Systems for Antimicrobial Resistance in Animal Bacterial Pathogens in Europe: A Basis for the Development of the European Antimicrobial Resistance Surveillance Network in Veterinary Medicine (EARS-Vet).

The monitoring of antimicrobial resistance (AMR) in bacterial pathogens of animals is not currently coordinated at European level. To fill this gap, experts of the European Union Joint Action on Antimicrobial Resistance and Healthcare Associated Infections (EU-JAMRAI) recommended building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet). In this study, we (i) identified national monitoring systems for AMR in bacterial pathogens of animals (both companion and food-producing) among 27 countries affiliated to EU-JAMRAI, (ii) described their structures and operations, and (iii) analyzed their respective strengths, weaknesses, opportunities and threats (SWOT). Twelve countries reported having at least one national monitoring system in place, representing an opportunity to launch EARS-Vet, but highlighting important gaps in AMR data generation in Europe. In total, 15 national monitoring systems from 11 countries were described and analyzed. They displayed diverse structures and operations, but most of them shared common weaknesses (e.g., data management and representativeness) and common threats (e.g., economic vulnerability and data access), which could be addressed collectively under EARS-Vet. This work generated useful information to countries planning to build or improve their system, by learning from others' experience. It also enabled to advance on a pragmatic harmonization strategy: EARS-Vet shall follow the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards, collect quantitative data and interpret AMR data using epidemiological cut-off values.

Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): a bottom-up and One Health approach.

BACKGROUND: Building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach. OBJECTIVES: To define the combinations of animal species/production types/age categories/bacterial species/specimens/antimicrobials to be monitored in EARS-Vet. METHODS: The EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the ECDC and the European Food Safety Authority (EFSA). RESULTS: EARS-Vet plans to monitor AMR in six animal species [cattle, swine, chickens (broilers and laying hens), turkeys, cats and dogs], for 11 bacterial species (Escherichia coli, Klebsiella pneumoniae, Mannheimia haemolytica, Pasteurella multocida, Actinobacillus pleuropneumoniae, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus hyicus, Streptococcus uberis, Streptococcus dysgalactiae and Streptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Molecular data detecting the presence of ESBLs, AmpC cephalosporinases and methicillin resistance shall be collected too. CONCLUSIONS: A preliminary EARS-Vet scope was defined, with the potential to fill important AMR monitoring gaps in the animal sector in Europe. It should be reviewed and expanded as the epidemiology of AMR changes, more countries participate and national monitoring capacities improve.

Treatment of clinical Brachyspira hyodysenteriae with zinc chelate in pigs: a blinded, randomised controlled trial.

BACKGROUND: Brachyspira hyodysenteriae infection in pigs ('swine dysentery') leads to decreased feed conversion, growth losses and mortality. Current countermeasures have the downside of antibiotic resistance (antibiotics) and ecotoxicity (zinc oxide). The aim of this study was to evaluate the effect of a novel zinc chelate (Intra Dysovinol (ID)) on clinical signs of swine dysentery and shedding of B hyodysenteriae under field conditions. METHODS: In a randomised, double-blinded, controlled trial under Good Clinical Practice on two commercial farms, 58 B hyodysenteriae positive pigs from 16 pens received drinking water containing ID, or placebo, during six consecutive days. Faecal quality (consistency, colour, additions) was scored and faeces were analysed for presence of B hyodysenteriae by PCR. ID treatment positively affected faecal quality (consistency) and daily growth rates. RESULTS: At the last treatment day, B hyodysenteriae was not detectable in the faeces of any of the ID-treated animals, while all placebo animals remained B hyodysenteriae positive by PCR. All ID-treated animals recovered, while 5 placebo-treated animals died and 12 placebo pigs required additional treatment before the end of the study (up to 14 days after treatment start). CONCLUSION: This non-antibiotic treatment stopped the clinical signs and shedding of B hyodysenteriae in naturally infected pigs.

Monitoring of antimicrobial susceptibility of Streptococcus suis in the Netherlands, 2013-2015.

The objective of the present study was to analyse the in vitro antimicrobial susceptibility of Streptococcus suis isolates from post-mortem samples from pigs in the Netherlands. S. suis isolates originated from diagnostic submissions of pigs sent to the Pathology Department of GD Animal Health, from April 2013 till June 2015. Minimal inhibitory concentrations (MICs) of in total 15 antimicrobials were assessed by broth microdilution following CLSI recommendations. MIC50 and MIC90 values were determined and MICs were interpreted as susceptible, intermediate and resistant using CLSI veterinary breakpoints (when available). Emergence of resistance among S. suis (n=1163) derived from clinical submissions of pigs appeared to be limited. Resistance to ampicillin, ceftiofur, clindamycin, enrofloxacin, florfenicol, penicillin, trimethoprim/sulfamethoxazole and tetracycline was 0.3%, 0.5%, 48.1%, 0.6%, 0.1%, 0.5%, 3.0%, and 78.4%, respectively. Cross-resistance between penicillin and ampicillin appeared to be incomplete. MIC values of erythromycin, clindamycin, neomycin, penicillin and tilmicosin for isolates originating from grower/finisher pigs were significantly more often lower than the MIC values of isolates from suckling/weaned piglets. It has to be kept in mind that these results represent only part of the Dutch pig population and it can be discussed whether this is a representative sample. Interpretation of the MIC results of (clinically relevant) antimicrobials tested for treatment of S. suis infection is strongly hampered by the lack of CLSI-defined veterinary clinical breakpoints that are animal species- and body site-specific. Therefore, and to conduct a clinically reliable monitoring of antimicrobial susceptibility of veterinary pathogens, more species- and organ-specific veterinary breakpoints are urgently needed.