Redefining cross-resistance, co-resistance and co-selection: beyond confusion?

The similarity of current definitions of 'cross-resistance' and 'co-resistance' continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations.

Antimicrobial Susceptibility of Canine and Feline Urinary Tract Infection Pathogens Isolated from Animals with Clinical Signs in European Veterinary Practices during the Period 2013-2018.

Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely hamper treatment success. Therefore, antimicrobial susceptibility monitoring is key.

Antimicrobial susceptibility among respiratory tract pathogens isolated from diseased cattle and pigs from different parts of Europe.

Aims: To survey antibiotic susceptibility of bacteria causing cattle and pig respiratory infections in 10 European countries.

Methods And Results: Non-replicate nasopharyngeal/nasal or lung swabs were collected from animals with acute respiratory signs during 2015-2016. Pasteurella multocida, Mannheimia haemolytica, Histophilus somni from cattle (n = 281), and P.

European regulations on prevention use of antimicrobials from january 2022.

Over the past several years significant progress on achieving better antibiotic stewardship in the veterinary sector has been achieved through regulatory legislations both in the USA and the European Union, including the implementation of US FDA GL 209 and 213. The EU is now taking measures to phase out the routine use of antibiotics for disease prevention, reserving prophylactic use for exceptional circumstances. This article intends to add some clarifications regarding antibiotics for disease prevention that are embedded in two EU regulations which came into force on 28th January 2022, Regulation (EU) 2019/4 on Medicated Feed and Regulation (EU) 2019/6 on Veterinary Medicinal Products.

European-wide antimicrobial resistance monitoring in commensal Escherichia coli isolated from healthy food animals between 2004 and 2018.

Objectives: To describe the susceptibility of Escherichia coli to medically important antibiotics, collected over four periods (2004-2006, 2008-2009, 2013-2014, 2017-2018), from food-producing animals at slaughter.

Methods: Intestinal contents from cattle, pigs and broilers were randomly sampled (5-6 countries/host; ≥4 abattoirs/country; one sample/animal/farm) for isolation of Escherichia coli; antimicrobial susceptibilities were centrally determined by CLSI agar dilution. Clinical breakpoints (CLSI) and epidemiological cut-off values (EUCAST) were applied for data interpretation.

Plasmid-mediated colistin resistance and ESBL production in Escherichia coli from clinically healthy and sick pigs.

This study aimed to determine the percentage of colistin resistant and ESBL-producing Escherichia coli from clinically sick and healthy pigs and understand the molecular mechanisms underlying colistin resistance and ESBL production. A total of 454 E. coli isolates from healthy pigs (n = 354; piglets, n = 83; fattening pigs, n = 142 and sows, n = 100) and sick pigs (n = 100) were examined for antimicrobial susceptibility, chromosomal and plasmid-mediated colistin resistance mechanisms and ESBL genes.

Can we align antibiotic policies at an international level in the absence of harmonized definitions?

The foundations of robust policies are reliant on harmonized definitions allowing consistency of understanding. However, it is evident that there is a lack of harmonization of definitions in the antibiotic space and even the simplest of terms such as 'antibiotic' and 'antimicrobial' do not have a single harmonized definition at an international level. This lack of harmonization makes interpretation of policies in different geographies a difficult, sometimes impossible, task.

Population-level analysis of antibiotic use and death rates in beef feedlots over ten years in three cattle-feeding regions of the United States.

Objective: To assess antibiotic use and other factors associated with death rates in beef feedlots in 3 regions of the US over a 10-year period.

Sample: Data for 186,297 lots (groups) of finished cattle marketed between 2010 and 2019 were obtained from a database representing feedlots in the central, high, and north plains of the US.

Procedures: Descriptive statistics were generated.

Comparative macrolide use in humans and animals: should macrolides be moved off the World Health Organisation's critically important antimicrobial list?

Macrolide antibiotics are categorized by the WHO as Highest Priority, Critically Important Antimicrobials due to their recommendation as treatment for severe cases of campylobacteriosis in humans; a self-limiting, rarely life-threatening, zoonotic foodborne infection. Low rates of macrolide resistance in Campylobacter jejuni and the availability of alternative treatments have prompted some regulatory schemes to assign macrolides to a lower importance category. Apart from rare, specific infections, macrolides largely play a supportive role to other drug classes in human medicine.

Antimicrobial susceptibility monitoring of Mycoplasma hyopneumoniae isolated from seven European countries during 2015-2016.

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia, a chronic respiratory disease, causing significant economic losses. Results from the 2015-2016 MycoPath pan-European antimicrobial susceptibility monitoring survey of M. hyopneumoniae are presented.

Minimal inhibitory concentration of seven antimicrobials to and isolates from six European countries.

and are bacterial pathogens that cause disease in poultry, adversely affecting their health and welfare, and are a financial burden on producers. This manuscript describes the results of the MycoPath project that is the first international antimicrobial susceptibility programme for mycoplasma pathogens isolated from poultry. Improved comparative analysis of minimal inhibitory concentration (MIC) results from participating countries was facilitated by using one laboratory determining all MICs.

Antimicrobial susceptibility monitoring of canine and feline skin and ear pathogens isolated from European veterinary clinics: results of the ComPath Surveillance programme.

Background: The ComPath project is a pan-European programme dedicated to the monitoring of antimicrobial susceptibility of canine and feline pathogens using standardized methods and centralized minimal inhibitory concentration (MIC) determination.

Objectives: To report antimicrobial susceptibilities of major pathogens isolated from nontreated animals with acute clinical signs of skin, wound or ear infections in 2013-2014.

Methods And Materials: MICs were determined by agar dilution for commonly used drugs and interpreted using Clinical and Laboratory Standards Institute (CLSI) breakpoints, if available.

Antimicrobial susceptibility of nine udder pathogens recovered from bovine clinical mastitis milk in Europe 2015-2016: VetPath results.

VetPath is an ongoing pan-European antimicrobial susceptibility monitoring programme collecting pathogens from diseased cattle, pigs and poultry not recently treated with antibiotics. Non-duplicate isolates (n = 1244) were obtained from cows with acute clinical mastitis in eight countries during 2015-2016 for centrally antimicrobial susceptibility testing according CLSI standards. Among Escherichia coli (n = 225), resistance was high to ampicillin and tetracycline, moderate to kanamycin and low to amoxicillin/clavulanic acid and cefazolin.

Antimicrobial resistance in a One Health context: exploring complexities, seeking solutions, and communicating risks.

Four articles presented in this special issue of Annals of the New York Academy of Sciences stem from a meeting of experts on antimicrobial resistance (AMR) in food animal production hosted by the New York Academy of Sciences on May 8 and 9, 2018. The articles discuss (1) competing considerations of the criticality of different classes of antimicrobials used for human and animal health and how guidelines and regulations might result in more prudent patterns of use; (2) the increasingly recognized importance of the environment (i.e.

Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture.

Globally, increasing acquired antimicrobial resistance among pathogenic bacteria presents an urgent challenge to human and animal health. As a result, significant efforts, such as the One Health Initiative, are underway to curtail and optimize the use of critically important antimicrobials for human medicine in all applications, including food animal production. This review discusses the rationale behind multiple and competing "critically important antimicrobial" lists and their contexts as created by international, regional, and national organizations; identifies discrepancies among these lists; and describes issues surrounding risk management recommendations that have been made by regulatory organizations on the use of antibiotics in food animal production.

Complexities in understanding antimicrobial resistance across domesticated animal, human, and environmental systems.

Antimicrobial resistance (AMR) is a significant threat to both human and animal health. The spread of AMR bacteria and genes across systems can occur through a myriad of pathways, both related and unrelated to agriculture, including via wastewater, soils, manure applications, direct exchange between humans and animals, and food exposure. Tracing origins and drivers of AMR bacteria and genes is challenging due to the array of contexts and the complexity of interactions overlapping health practice, microbiology, genetics, applied science and engineering, as well as social and human factors.

Antimicrobial resistance monitoring in commensal enterococci from healthy cattle, pigs and chickens across Europe during 2004-14 (EASSA Study).

Objectives: The European Antimicrobial Susceptibility Surveillance in Animals (EASSA) programme collects zoonotic and commensal bacteria from healthy food-producing animals at slaughter and tracks their susceptibility to medically important antibiotics. Results for enterococci, collected over three time periods, are presented.

Methods: Intestinal contents from cattle, pigs and chickens were randomly sampled (five or six countries/host; at least four abattoirs/country; one sample/animal/farm) for isolation of enterococci; antimicrobial susceptibilities were centrally assessed by CLSI agar dilution.

Antimicrobial susceptibility of enterococci recovered from healthy cattle, pigs and chickens in nine EU countries (EASSA Study) to critically important antibiotics.

The European Antimicrobial Susceptibility Surveillance in Animals (EASSA) program collects zoonotic and commensal bacteria from food-producing animals at slaughter and tracks their susceptibility to medically important antibiotics. Results of commensal enterococci species (2013-2014) are presented here. Intestinal content from cattle, pigs and chickens were randomly sampled (5-6 countries/host; ≥4 abattoirs/country; 1 sample/animal/farm) for isolation of enterococci, MICs of 9 antibiotics were assessed by CLSI agar dilution in a central laboratory.

Monitoring of antimicrobial susceptibility of udder pathogens recovered from cases of clinical mastitis in dairy cows across Europe: VetPath results.

VetPath is an ongoing pan-European antimicrobial susceptibility monitoring programme collecting pathogens from diseased cattle, pigs and poultry not recently treated with antibiotics. Non-duplicate milk samples were collected from cows with acute clinical mastitis in nine countries and 934 isolates were obtained during 2009-2012 for subsequent antimicrobial susceptibility testing in a central laboratory. CLSI broth microdilution methodology was used, and where available, MICs were interpreted using CLSI approved veterinary-specific (ceftiofur) otherwise human clinical breakpoints.

Monitoring of antimicrobial susceptibility of respiratory tract pathogens isolated from diseased cattle and pigs across Europe, 2009-2012: VetPath results.

VetPath is an ongoing pan-European antibiotic susceptibility monitoring programme that collects pathogens from diseased cattle, pigs and poultry. In the current study, 996 isolates from cattle and pig respiratory tract infections were tested for their antimicrobial susceptibilities. Non-replicate lung samples or nasopharyngeal/nasal swabs were collected from animals with acute clinical signs in 10 countries during 2009-2012.

Antimicrobial susceptibility monitoring of mastitis pathogens isolated from acute cases of clinical mastitis in dairy cows across Europe: VetPath results.

VetPath is an ongoing pan-European antimicrobial susceptibility monitoring programme collecting pathogens from diseased cattle, pigs and poultry not recently treated with antibiotics. Non-replicate milk samples were collected from cows with acute clinical mastitis in eight countries. Escherichia coli, Staphylococcus aureus and Streptococcus uberis were isolated by standardised methods.

Antimicrobial susceptibility monitoring of respiratory tract pathogens isolated from diseased cattle and pigs across Europe: the VetPath study.

VetPath is an ongoing pan-European antibiotic susceptibility monitoring programme collecting pathogens from diseased antimicrobial non-treated cattle, pigs and poultry. In the current study, 1001 isolates from cattle and pig respiratory tract infections were tested for their antimicrobial susceptibilities. Non-replicate lung samples or nasopharyngeal/nasal swabs were collected from animals with acute clinical signs in 11 countries during 2002-2006.

Antimicrobial resistance monitoring projects for zoonotic and indicator bacteria of animal origin: common aspects and differences between EASSA and EFSA.

Resistance monitoring programmes are essential to generate data for inclusion in the scientific risk assessment of the potential for transmission of antimicrobial-resistant bacteria or their resistance determinants from food-producing animals to humans. This review compares the technical specifications on monitoring of antimicrobial resistance in zoonotic Salmonella, Campylobacter and indicator Escherichia coli and Enterococcus as performed by the European Food Safety Authority (EFSA) with veterinary pharmaceutical industry's European Antimicrobial Susceptibility Surveillance in Animals (EASSA) programme. The authors conclude that most of EFSA's recent monitoring recommendations have been covered by EASSA since the start of the latter programme in 1998.

Reversible monensin adaptation in Enterococcus faecium, Enterococcus faecalis and Clostridium perfringens of cattle origin: potential impact on human food safety.

Objectives: To determine the stability/reversibility and mechanism of monensin adaptation in monensin-treated cattle isolates compared with reference bacterial isolates, exposed in vitro to high monensin concentrations.

Methods: We evaluated the potential for cattle-origin strains of Clostridium perfringens, Enterococcus faecium and Enterococcus faecalis exposed to monensin in vivo (in vivo monensin-exposed isolates) to maintain or achieve the ability to grow in the presence of high monensin concentrations (in vitro monensin-adapted isolates). Twenty-one consecutive subcultures of the in vitro monensin-adapted strains were performed, and monensin MICs were determined for the 3rd, 7th, 14th and 21st subcultures (subcultured isolates).