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.

No change in avilamycin (Surmax® Premix) minimum inhibitory concentration for Clostridium perfringens isolates recovered from poultry up to 7 years post-approval in Canada.

BACKGROUND: Clostridium perfringens, the causative agent of necrotic enteritis (NE) in chickens, has an enormous economic impact on global broiler production. The non-medically important antibiotic avilamycin was approved in Canada in 2014 to prevent and control NE in broiler chickens. OBJECTIVES: To compare avilamycin susceptibility in C. perfringens isolates collected pre- and 7 years post-avilamycin approval in Canada and determine the avilamycin resistance mutation frequency rate in C. perfringens. METHODS: The MICs of avilamycin were determined for 89 strains of C. perfringens recovered from clinically relevant NE field cases pre-avilamycin approval between 2003 and 2013 (n = 50) and post-avilamycin approval between 2014 and 2021 (n = 39) across Canada. For determining the mutant prevention concentration (MPC) of avilamycin for C. perfringens strains, a strain with avilamycin MIC of 1 mg/L was randomly selected. RESULTS: MIC studies showed no difference in avilamycin susceptibility in pre-avilamycin and post-avilamycin isolates (MIC50/90: pre-avilamycin approval 2/2 mg/L and post-avilamycin approval 1/2 mg/L). The MPC was 8 × MIC (8 mg/L) for the selected strain. CONCLUSIONS: These findings suggest that the susceptibility of C. perfringens strains to avilamycin was not impacted by its continued use in the 7 years following its approval in Canada. Avilamycin, a non-medically important antibiotic, poses no threat to human health regarding cross-resistance or co-selection of other medically important antibiotics. These factors make avilamycin an appropriate choice for continued use in broiler chickens to prevent and control NE without increased antimicrobial resistance concerns.

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. multocida, Actinobacillus pleuropneumoniae, Glaesserella parasuis, Bordetella bronchiseptica, and Streptococcus suis from pigs (n = 593) were isolated. MICs were assessed following CLSI standards and interpreted using veterinary breakpoints where available. Histophilus somni isolates were fully antibiotic susceptible. Bovine P. multocida and M. haemolytica were susceptible to all antibiotics, except tetracycline (11.6%-17.6% resistance). Low macrolide and spectinomycin resistance was observed for P. multocida and M. haemolytica (1.3%-8.8%). Similar susceptibility was observed in pigs, where breakpoints are available. Resistance in P. multocida, A. pleuropneumoniae, and S. suis to ceftiofur, enrofloxacin, and florfenicol was absent or <5%. Tetracycline resistance varied from 10.6% to 21.3%, but was 82.4% in S. suis. Overall multidrug-resistance was low. Antibiotic resistance in 2015-2016 remained similar as in 2009-2012. CONCLUSIONS: Low antibiotic resistance was observed among respiratory tract pathogens, except for tetracycline.

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. This article proposes a set of definitions that could be adopted by international institutions such as the WHO, World Organisation for Animal Health (OIE) and Food and Agriculture Organisation (FAO) as well as regulatory agencies.

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. RESULTS: In total, 10 613 E. coli strains were recovered. In broilers, resistance percentages were the lowest (P ≤ 0.01) in the latest time period. A significant decrease in MDR over time was also observed for broilers and a tendency for a decrease for pigs. Resistance to meropenem and tigecycline was absent, and resistance to azithromycin was 0.2%-2.0%. Also, low resistance to third-generation cephalosporins (1.1%-7.4%) was detected in broilers. Resistance to colistin varied between 0.1%-4.8%. E. coli from broilers showed high resistance to ciprofloxacin (7.3%-23.3%), whereas for cattle and pigs this was 0.2%-2.5%. Low/moderate resistance to chloramphenicol (9.3%-21.3%) and gentamicin (0.9%-7.0%) was observed in pigs and broilers. The highest resistance was noted for ampicillin (32.7%-65.3%), tetracycline (41.3%-67.5%), trimethoprim (32.0%-35.7%) and trimethoprim/sulfamethoxazole (27.5%-49.7%) from pigs and broilers, with marked country differences. MDR peaked in pigs and broilers with 24 and 26 phenotypes, with 21.9%-26.2% and 18.7%-34.1% resistance, respectively. CONCLUSIONS: In this pan-EU survey antibiotic susceptibility of commensal E. coli varied largely between antibiotics, animal species and countries. Resistance to critically important antibiotics for human medicine was absent or low, except for ciprofloxacin in broilers and ampicillin in pigs and broilers.

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. By contrast, although the advent of alternative control methods has seen significant reductions in macrolide use in intensive livestock, they still have a crucial role in the treatment/control of respiratory infections and liver abscesses in cattle. Whilst acknowledging that ongoing surveillance is required to reduce the spread of recently emerged, transferable macrolide resistance among Campylobacter, this article recommends that macrolides should be moved to the WHO Highly Important category.

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

Mycoplasma gallisepticum and Mycoplasma synoviae 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. Chicken and turkey isolates were obtained from France, Germany, Great Britain, Hungary, Italy and Spain during 2014-2016. One isolate per farm was retained. The MIC of seven antimicrobial agents was determined using a broth microdilution method, with Friis Medium (M. gallisepticum) or Modified Chanock's Medium (M. synoviae). Of the 222 isolates recovered, 82 were M. gallisepticum and 130 were M. synoviae. M. gallisepticum MIC50/90 values were 0.12/0.5, 2/8, 0.5/4, 0.12/>64, 0.008/0.062, 0.008/32, 0.062/4 mg/l for doxycycline, enrofloxacin, oxytetracycline, spiramycin, tiamulin, tilmicosin and tylosin, respectively. For M. synoviae, the values were 0.5/1, 8/16, 0.5/1, 0.5/8, 0.25/0.5, 0.062/2 and 0.062/16 mg/l respectively. A bimodal MIC distribution for the fluoroquinolone (enrofloxacin) and the macrolides (spiramycin, tilmicosin and tylosin) indicate that both species have sub-populations that are less susceptible in vitro to those antimicrobials. Some differences in susceptibilities were observed according to host species, Mycoplasma species, and country of origin. This study provides a baseline of novel data for future monitoring of antimicrobial resistance in poultry Mycoplasma species. Additionally, this information will facilitate the selection of the antimicrobial agents most likely to be effective, thus ensuring their minimal use with targeted and correct therapeutic treatments.Highlights First large-scale pan-European collection of representative Mg and Ms isolates.MIC values assessed in central laboratory for Mg and Ms from chickens and turkeys.Range of MIC values for 82 Mg and 130 Ms isolates to seven licenced antibiotics shown.Data can be used to help determine Mg and Ms veterinary-specific breakpoints.

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. RESULTS: Of 1,676 isolates recovered, the main species isolated from dogs were Staphylococcus pseudintermedius, followed by Streptococcus spp., Pseudomonas aeruginosa and Escherichia coli. In cats, Pasteurella multocida, coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were isolated most frequently. Resistance rates observed for S. pseudintermedius were <26.7% for penicillin, clindamycin and chloramphenicol, and ≤11.5% for ampicillin, amoxicillin/clavulanate, cefalexin, cefovecin, gentamicin and fluoroquinolones. For S. aureus, resistance rates ranged up to 90.9% for ß-lactams, and were 19.7% for clindamycin, 27% for fluoroquinolones and 0.0-6.1% for other drugs. The mecA gene was confirmed by PCR in 10.6% of S. pseudintermedius, 11.6% of CoNS and 31.4% of S. aureus isolates. In streptococci/enterococci, resistance to penicillin, ampicillin and chloramphenicol ranged from 0.0% to 11.3%, whereas fluoroquinolone resistance ranged from 0.0% to 8.5%. For E. coli, resistance ranged from 13.8 to 15.9% for fluoroquinolones and from 86.2% to 100.0% for ß-lactams. Low rates of resistance (0.0-6.3%) were observed in P. multocida, and for P. aeruginosa resistance to gentamicin was 10.3%. CONCLUSION: Overall, antimicrobial resistance of cutaneous/otic pathogens isolated from dogs and cats was low (1-10%) to moderate (10-20%). For several pathogens, the paucity of CLSI recommended breakpoints for veterinary use is a bottleneck.

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. Clinical breakpoints (CLSI) and epidemiological cut-off values (EUCAST) were applied for data interpretation. RESULTS: In total, 2435 Enterococcus faecium and 1389 Enterococcus faecalis strains were recovered. Seven E. faecium/faecalis strains were linezolid resistant. One E. faecium strain was non-WT (NWT), with a daptomycin MIC of 8 mg/L. Clinical vancomycin resistance was very low or absent; eight strains had decreased susceptibility (MICs of 8 mg/L). Two strains were clinically resistant to tigecycline. Little resistance to ampicillin or gentamicin was observed. Clinical resistance of E. faecium to quinupristin/dalfopristin was slightly higher (2.2%-33.6%) and 38.5%-83.2% of the strains were classified NWT. Very high resistance to tetracycline (67.4%-79.1%) and erythromycin (27.1%-57.0%) was noted for E. faecium and E. faecalis in pigs and chickens. For both of these compounds, similar NWT results were observed for Enterococcus hirae (n = 935), Enterococcus durans (n = 286) and Enterococcus casseliflavus (n = 154) whereas the percentage of NWT for linezolid, tigecycline and vancomycin was generally zero or low. CONCLUSIONS: In this pan-EU survey of commensal enterococci, antibiotic susceptibility varied widely between antibiotics, animal species, countries and enterococcal species. Clinical resistance to antibiotics that are critically important for human medicine was absent or low, except for erythromycin.

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. UTI isolates were obtained from dogs and cats in two collection periods (ComPath II: 2013-2014 and ComPath III: 2017-2018) as part of CEESA's ComPath programme. Susceptibility testing of the UTI isolates (2021 in total) was carried out at one central laboratory using agar and broth dilution methodology as recommended by the Clinical and Laboratory Standards Institute. Escherichia coli was the most frequently isolated bacterium in UTI in both dogs (46.9%, 43.1%) and cats (61.2%, 48.3%) across ComPath II and ComPath III, respectively. The percentage of resistance in E. coli was low (<10%) across both programmes in both dogs and cats except for trimethoprim-sulfamethoxazole (dogs ComPath III: 12.9%; cats ComPath II: 13.0%) and enrofloxacin (10.5%), marbofloxacin (11.4%), and doxycycline (98.8%) for dogs in ComPath III. Three (7.5%) of the 40 isolated S. aureus bacteria in total were MRSA and harboured mecA. The level of multidrug resistance (MDR) was generally low and ranged from 0.0% for feline coagulase-negative Staphylococcus spp. to 11.7% for canine Proteus spp., except for a peak of MDR observed in canine Klebsiella isolates from ComPath II (36.7%). Overall, antimicrobial resistance for most canine and feline UTI pathogens isolated during the ComPath II and ComPath III programmes was low (1-10%) to moderate (10-20%).

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). SDS-PAGE and transmission electron microscopy (TEM) were used to determine protein expression and visualize extracellular morphology changes. RESULTS: Monensin-non-exposed isolates did not display monensin adaptation during in vitro monensin exposure. In contrast, in vivo monensin-exposed isolates displayed monensin adaptation enabling growth at 32× MIC. Upon consecutive subculturing, monensin MICs returned to baseline, or one dilution above, for the monensin-adapted strains. SDS-PAGE identified overexpression of a 14 kDa protein (C. perfringens) and a 20.5 kDa protein (E. faecium and E. faecalis) in the monensin-adapted isolates. TEM demonstrated that in vitro monensin-adapted strains had a significantly thicker cell wall or glycocalyx compared with in vivo monensin-exposed or subcultured isolates. CONCLUSIONS: In vivo monensin-exposed isolates of C. perfringens, E. faecium and E. faecalis have the ability to grow in the presence of high monensin concentrations in vitro. This is associated with an increased thickening of the cell wall or glycocalyx that is reversible upon serial passage, suggesting a phenotypically expressed, but not genetically stable, trait.

Pan-European monitoring of susceptibility to human-use antimicrobial agents in enteric bacteria isolated from healthy food-producing animals.

OBJECTIVES: To determine the antimicrobial susceptibility of Escherichia coli, Salmonella, Campylobacter and Enterococcus from cattle, pigs and chickens across the European Union (EU) using uniform methodology. METHODS: Intestinal samples (1624) were taken at slaughter across five EU countries. Bacteria were isolated in national laboratories, whilst MICs were determined in a central laboratory for key antimicrobials used in human medicine. Clinical resistance was based on CLSI breakpoints and decreased susceptibility based on European Food Safety Authority (EFSA)/EUCAST epidemiological cut-off values. RESULTS: Isolation rates were high for E. coli (n=1540), low for Salmonella (n=201) and intermediate for Campylobacter (n=940) and Enterococcus (n=786). For E. coli and Salmonella, clinical resistance to newer compounds (cefepime, cefotaxime and ciprofloxacin) was absent or low, but decreased susceptibility was apparent, particularly in chicken strains. Resistance to older compounds (except gentamicin) was variable and higher. Colistin resistance was absent for E. coli, but apparent for Salmonella. For Campylobacter jejuni, ciprofloxacin resistance was markedly prevalent for chickens, whereas clinical resistance and decreased susceptibility to erythromycin was absent or very low. For Campylobacter coli, resistance was notably higher. None of the Enterococcus faecium strains was resistant to linezolid, but some were resistant to ampicillin or vancomycin. Resistance to quinupristin/dalfopristin was frequent. CONCLUSIONS: Resistance patterns varied widely depending on bacterial species, antibiotics, hosts and region. Resistance varied among countries, particularly for older antimicrobials, but clinical resistance to newer antibiotics used to treat foodborne disease in humans was generally very low. In the absence of resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored.

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.

Ao longo dos últimos anos, progressos significativos na obtenção de uma melhor administração de antibióticos no setor veterinário foram alcançados por meio de legislações regulatórias nos EUA e na União Européia, incluindo a implementação do FDA GL 209 e 213 dos EUA. o uso rotineiro de antibióticos para prevenção de doenças, reservando o uso profilático para circunstâncias excepcionais. Este artigo pretende adicionar alguns esclarecimentos sobre antibióticos para prevenção de doenças que estão inseridos em dois regulamentos da UE que entraram em vigor em 28 de janeiro de 2022, Regulamento (UE) 2019/4 sobre alimentos medicamentosos para animais e Regulamento (UE) 2019/6 sobre medicamentos veterinários.

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. The healthy (41%) and sick pig (73%) isolates were commonly resistant to colistin. Three mcr genes including mcr-1 (10.4%), mcr-2 (1.1%) and mcr-3 (45%) were detected, of which mcr-3 was most frequently detected in the healthy (33%) and sick pig (57%) isolates. Coexistence of mcr-1/mcr-3 and mcr-2/mcr-3 was observed in piglets (23%), fattening pig (3.5%) and sick pig (13%) isolates. Three amino acid substitutions including E106A and G144S in PmrA and V161G in PmrB were observed only in colistin-resistant isolates carrying mcr-3. The percentage of ESBL-producing E. coli was significantly higher in the sick pigs (44%) than the healthy pigs (19.2%) (P = 0.00). The blaCTX-M group was most prevalent (98.5%), of which blaCTX-M-14 (54.5%) and blaCTX-M-55 (42.9%) were predominant. The blaTEM-1 (68.8%) and blaCMY-2 (6.3%) genes were identified in ESBL-producers. All ESBL producers were multidrug resistant and the majority from piglets (97%), fattening pigs (77.3%) and sick pigs (82%) carried mcr gene (s). ESBL producers from piglets (n = 5) and sick pig (n = 1) simultaneously transferred blaTEM-1 (or blaCTX-M-55) and mcr-3 to Salmonella. In conclusion, pigs are important reservoirs of colistin-resistant E. coli that also produced ESBLs, highlighting the need for prudent and effective use of antimicrobials in pigs and other food-producing animals.

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. Generalized linear mixed models were used to estimate lot death rates for each region, sex (steer or heifer), and cattle origin (Mexico or the US) combination. Death rate was calculated as the (number of deaths/number of cattle placed in the lot) × 100. Lot antibiotic use (TotalActiveMG/KGOut) was calculated as the total milligrams of active antibiotics assigned to the lot per live weight (in kilograms) of cattle marketed from the lot. Rate ratios were calculated to evaluate the respective associations between lot death rate and characteristics of cattle and antibiotic use. RESULTS: Mean death rate increased during the 10-year period, peaking in 2018. Mean number of days on feed also increased over time. Mean TotalActiveMG/KGOut was greatest in 2014 and 2015, lowest in 2017, and moderated in 2018 and 2019. Death rate was positively associated with the number of days on feed and had a nonlinear association with TotalActiveMG/KGOut. Feeding medicated feed articles mitigated death rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested a balance between disease prevention and control in feedlots for cattle with various risk profiles. Additional data sources are needed to assess TotalActiveMG/KGOut across the cattle lifetime.

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. In total, 147 M. hyopneumoniae porcine isolates from Belgium, France, Germany, Great Britain, Hungary, Italy, and Spain were tested. One isolate per farm was retained from pigs that had not been recently treated with antimicrobial agents. The minimal inhibitory concentration (MIC) of 13 antimicrobial agents was determined in a central laboratory using a broth microdilution method, with Friis Medium, incubated at 35 ± 1 °C for 5-12 days. M. hyopneumoniae NCTC 10110 was used as Quality Control. MIC50/MIC90 (mg/L) values were: enrofloxacin 0.06/1; marbofloxacin 0.06/2; spiramycin 0.06/0.25; tulathromycin ≤0.001/0.004; gamithromycin 0.06/0.5; tylosin 0.016/0.06; tilmicosin 0.06/0.5; florfenicol 0.5/1; doxycycline 0.25/1; oxytetracycline 0.25/2; lincomycin 0.06/0.25; tiamulin 0.016/0.06 and valnemulin ≤0.001/0.004. Compared with the data from 2010 to 2012 MycoPath study (50 isolates), MIC50/90 results were similar and the majority were within ± two dilution steps, except for the MIC50 of oxytetracycline which is more than two dilution steps higher in the present study. Between-country comparisons show some differences in the MIC values for the fluoroquinolones, tulathromycin and tylosin, but the limited sample size per country precludes performing meaningful country comparisons for several countries. Standardized laboratory methods and interpretive criteria for MIC testing of veterinary mycoplasmas are clearly needed; there are currently no clinical breakpoints available to facilitate data interpretation and correlation of MICs with in vivo efficacy.

Editorial: assessing the antimicrobial susceptibility of bacteria obtained from animals.

The accurate performance of antimicrobial susceptibility testing of bacteria from animal sources and the correct presentation of the results is a complex matter. A review of the published literature revealed a number of recurring errors with regard to methodology, quality control, appropriate interpretive criteria, and calculation of MIC(50) and MIC(90) values. Although more subjective, there is also no consensus regarding the definition of multiresistance. This Editorial is intended to provide guidance to authors on how to avoid these frequently detected shortcomings.

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. The MIC50/90 of danofloxacin, enrofloxacin and marbofloxacin were 0.03 and 0.06 µg/mL. For Klebsiella spp. (n = 70), similar results were noted, except for ampicillin and kanamycin. We detected 3.7 % (11/295) Enterobacteriaceae isolates carrying an ESBL/AmpC gene. Staphylococcus aureus (n = 247) and coagulase-negative staphylococci (CoNS; n = 189) isolates were susceptible to most antimicrobials tested except to penicillin (25.1 and 29.1 % resistance). Two S. aureus and thirteen CoNS isolates harboured mecA gene. Streptococcus uberis isolates (n = 208) were susceptible to ß-lactam antibiotics (87.1-94.7 % susceptibility), 23.9 % were resistant to erythromycin and 37.5 % to tetracycline. Resistance to pirlimycin was moderate. For Streptococcus dysgalactiae (n = 132) the latter figures were 10.6 and 43.2 %; pirlimycin resistance was low. MIC values for Streptococcus agalactiae, Trueperella pyogenes and Corynebacterium spp. were generally low. This current VetPath study shows that mastitis pathogens were susceptible to most antimicrobials with exceptions of staphylococci against penicillin and streptococci against erythromycin or tetracycline. For most antimicrobials, the percentage resistance and MIC50/90 values among the major pathogens were comparable to that of the preceeding VetPath surveys. This work highlights the high need to set additional clinical breakpoints for antimicrobials frequently used to treat mastitis.

A pan-European survey of antimicrobial susceptibility towards human-use antimicrobial drugs among zoonotic and commensal enteric bacteria isolated from healthy food-producing animals.

OBJECTIVES: The aim of the study was to study antimicrobial susceptibility in Escherichia coli, Salmonella, Campylobacter and Enterococcus recovered from chickens, pigs and cattle using uniform methodology. METHODS: Intestinal samples were taken at slaughter in five EU countries per host and bacteria isolated in national laboratories. MICs were determined in a central laboratory of key antimicrobials used in human medicine. Clinical resistance was based on CLSI breakpoints and decreased susceptibility on EFSA epidemiological cut-off values. RESULTS: Isolation rates from a total of 1500 samples were high for E. coli (n=1465), low for Salmonella (n=205) and intermediate for Campylobacter (n=785) and Enterococcus (n=718). Resistance prevalence varied among antibiotics, bacteria, hosts and countries. For E. coli and Salmonella, clinical resistance to newer compounds (cefepime, cefotaxime, ciprofloxacin) was absent or low, but a decreased susceptibility was apparent, particularly in chickens. Clinical resistance to older compounds (except colistin and gentamicin) was variable and higher. For Campylobacter jejuni from chickens, ciprofloxacin resistance was markedly higher than in isolates from cattle. Clinical resistance to erythromycin was absent for both hosts; decreased susceptibility very low. Similar trends were determined for Campylobacter coli, but C. jejuni was less resistant. None of the enterococcal strains was resistant to linezolid, but a few displayed resistance to ampicillin or vancomycin. Resistance prevalence to quinupristin/dalfopristin was clearly higher. CONCLUSIONS: Antimicrobial resistance among enteric organisms in food animals varied among countries, particularly for older antimicrobials, but clinical resistance to essential compounds used to treat disease in humans was generally zero or low. In the absence of clinical resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored carefully.

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., soil, water, and air) as a reservoir of resistant bacteria and resistance genes as well as a pathway for the dissemination of AMR between human and animal host populations; (3) established and novel solutions for measuring and containing the AMR problem; and (4) effective strategies for communicating to consumers the risks of AMR spreading from food production and other nonhuman sources. The authors of this commentary served as the scientific advisory committee to the meeting.