Use In Food-producing Animals Research Articles

Evaluation of antibiotic usage in swine reproduction farms in Umbria region based on the quantitative analysis of antimicrobial consumption.

Antibiotic use in food-producing animals has considerable impact on public health, especially with respect to the development and spread of antibiotic resistance. Pigs represent one of the main species in which antibiotics are frequently used for different purposes. Surveillance of antibiotic consumption and dose appropriateness, through novel approaches based on defined daily doses, is strongly needed to assess farms’ antibiotic risk, in terms of spread of antibiotic resistance and possibile presence of residues in meat. In this study, antibiotic consumption was monitored in 14 swine reproduction farms, together with managerial, structural, and health aspects. Most of the controlled farms (65%) were classified as at medium antibiotic risk, 21% at high antibiotic risk, and 14% at low antibiotic risk. Critical aspects of antibiotic administration concerned treatments for suckling and weaner piglets, oral antibiotic administration, treatment and diagnosis of gastroenteric infections, and use of critically important antimicrobials for human medicine, especially colistin. These aspects could be considered critical aspects of antibiotic use in from-farrow-to-wean/finish swine farms in the Umbria region and must be controlled to minimize risks. Even though a small number of farms in Umbria region are at high antibiotic risk, the risk of antibiotic resistance should be minimized, and management and biosecurity of the farms should be improved by extending the use of antimicrobial susceptibility tests and optimizing the diagnostic methods for infectious diseases. Furthermore, farmers’ and veterinarians’ knowledge of antibiotic resistance should be improved and the prudent use of antibiotics encouraged to prevent the development and spread of resistant microorganisms.

Antimicrobial use in food-producing animals: a rapid evidence assessment of stakeholder practices and beliefs

Food-producing animals throughout the world are likely to be exposed to antimicrobial (AM) treatment. The crossover in AM use between human and veterinary medicine raises concerns that antimicrobial resistance (AMR)...

Enantioselective analysis of chloramphenicol residues in honey samples by chiral LC-MS/MS and results of a honey survey

ABSTRACTChloramphenicol (CAP) is a broad-spectrum antibiotic used widely in both human and veterinary medication. Since 1994, CAP has not been authorised for use in food-producing animals in the European Union due to several adverse effects. A minimum required performance level (MRPL) of 0.3 µg kg–1 was established in 2003. The CAP molecule contains two asymmetric centres, thus in total four para-CAP stereoisomers exist. Only the RR-CAP enantiomer is bioactive, having significant antimicrobial activity. For the first time a chiral LC-MS/MS method is reported to identify and quantify the four CAP enantiomers at residue levels in honey samples. The method was validated at two concentration levels. The decision limits (CCα) and detection capabilities (CCß) were well below 0.3 µg kg–1, with limits of quantification (LOQs) between 0.08 and 0.12 µg kg–1 for all four enantiomers. The method provides a sensitive and reliable analysis of CAP enantiomers in honey, and proved its robustness during the daily routine analyses of numerous honey samples. In an internal honey survey, in total 40 honey samples from different geographical regions with identified CAP residues at or above the MRPL were reanalysed by chiral LC-MS/MS. In nine honey samples only the bioactive RR-CAP was detected as anticipated. However, in all other 31 honey samples the non-bioactive SS-CAP was also identified and quantified unambiguously. In 10 of these samples, mixtures of RR- and SS-CAP were analysed, and in 21 samples only the SS-CAP enantiomer, with concentrations up to 2.2 µg kg–1. Most of these samples are honeys from Ukraine and Eastern Europe. This is the first report of SS-CAP residues in food samples. The potential sources for these findings are discussed and the need of further systematic studies emphasised. It is recommended to examine in more depth the toxicological profile of the individual CAP stereoisomers.

Metronidazole for the treatment ofTritrichomonas foetusin bulls

BackgroundTritrichomonas foetusis a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA).ResultsResults from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovineTritrichomonas foetus.The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive forTritrichomonas foetusculture at weekly intervals for 5 weeks prior to treatment was negative forTritrichomonas foetusculture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treatTritrichomonas foetusin bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls.ConclusionThe study demonstrated successful inhibition of Tritrichomonas foetusboth in vitro and in vivo with metronidazole. The current status of metronidazole is that the Animal Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in food-producing animals. Veterinarians and regulators should consider approaches that might lead to permitting the legal use of metronidazole in bulls.

Optimization of a multiresidue and multiclass analysis method for anabolic agents and β2-agonists in bovine urine by GC-MS/MS

A simple multiresidue and multiclass procedure is described for the simultaneous determination of anabolic agents and β2-agonists from 4 classes of prohibited substances of illegal use in food-producing animals, according to Council Directive 96/23/EC. The method involves analysis of hydrolysed urinary anabolic compounds using liquid–liquid extraction, with subsequent conversion to trimethylsilylether derivatives that are analysed by GC-MS/MS.The oven was set to an initial temperature of 140°C, was increased at a rate of 10°C/min to 300°C, and was held 3 min using an Ultra-1 capillary column. Optimization tests demonstrated good peak resolution and shape for all compounds. A pre-validation study was conducted to obtain an analytical test curve, which showed adequate results for all analytes. Cochran's test (C calculated <0.6838, 95% confidence interval) proved the homoscedasticity of all the compounds. The results for the apparent recovery of each analyte, calculated for the five fortification levels of the analytical curve, varied between 94.7% and 109.3%. The limit of quantitation was 0.5 times the minimum required performance limit (MRPL), and the limit of detection was 0.33 times the MRPL.

Commentary: Benefits and risks of antimicrobial use in food-producing animals.

Commentary: Benefits and risks of antimicrobial use in food-producing animals.

Addressing Antimicrobial Resistance: An Overview of Priority Actions to Prevent Suboptimal Antimicrobial Use in Food-Animal Production.

The growing concern regarding emergence of bacteria resistant to antimicrobials and their potential for transmission to humans via animal production has led various authorities worldwide to implement measures to decrease antimicrobial use (AMU) in livestock production. These measures are influenced by those implemented in human medicine, and emphasize the importance of antimicrobial stewardship, surveillance, infection prevention and control and research. In food producing animals, unlike human medicine, antimicrobials are used to control diseases which cause economic losses. This major difference may explain the failure of the public policies implemented to control antimicrobial usage. Here we first review the specific factors influencing AMU across the farm animal sector and highlighting the farmers’ decision-making process of AMU. We then discuss the efficiency of existing regulations implemented by policy makers, and assess the need for alternative strategies, such as substitution between antimicrobials and other measures for infectious disease control. We also discuss the interests of regulating antimicrobial prices. Finally, we emphasize the value of optimizing antimicrobial regimens, and developing veterinary precision medicine to achieve clinical efficacy in animals while limiting negative impacts on public health. The fight against antimicrobial resistance requires both a reduction and an optimization of antimicrobial consumption. The set of actions currently implemented by policy makers does not adequately address the economic interests of farmers’ use of antimicrobials.

Photoresponsive colorimetric immunoassay based on chitosan modified AgI/TiO2 heterojunction for highly sensitive chloramphenicol detection

Chloramphenicol (CAP) is an antibiotic used for a variety of infections, however, it is banned for use in food-producing animals due to its hazards to humans blood. Herein, the highly sensitive photoresponsive colorimetric immunoassay was exploited based on AgI/TiO2 heterojunction nanomaterials. Firstly, chitosan modified AgI/TiO2 photocatalyst (CS-AgI/TiO2) was synthesized by deposition-precipitation method, which was characterized by transmission electron microscope (TEM), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (DRS) and Fourier transform infrared spectroscopy (FTIR). Then, by utilizing CS-AgI/TiO2 labeled CAP antibody as tags, a novel competitive-type immunoassay was constructed for detection of CAP on the surface of CAP-BSA modified magnetic bead. The color development of 3,3′,5,5′-tetramethylbenzidine (TMB) was obtained under visible light irradiation (λ≥420nm) and the assay was carried out in pH 3.0 ABS buffer solution by UV–Vis spectrophotometry. Under optimal conditions, the absorbance values decreased with the increasing of CAP levels in sample, which exhibited linear in the range of 0.03–12.53nM with a detection limit of 0.03nM. Meanwhile, the selectivity, repeatability, and stability were acceptable. Excitedly, no significant difference was observed for detection of the spiked CAP in the real food samples with the referenced values.

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses

ABSTRACTToxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg–1 for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Malachite green in food

Malachite green (MG) has been used globally in aquaculture but is not registered for use in food-producing animals in the European Union. The European Commission requested EFSA to evaluate whether a reference point for action (RPA) of 2 μg/kg for the sum of MG and its major metabolite leucomalachite green (LMG) is adequate to protect public health. Available occurrence data were not suitable for a reliable exposure assessment. The hypothetical dietary exposure was calculated, considering the RPA as occurrence value for all types of fish, fish products and crustaceans. Mean dietary exposure across different European dietary surveys and age classes would range from 0.1 to 5.0 ng/kg body weight (bw) per day. For high and frequent fish consumers, the exposure would range from 1.3 to 11.8 ng/kg bw per day. Both MG and LMG induced formation of DNA adducts in livers of rats and/or mice, and of micronuclei in mice. LMG also induced cII transgene mutations in mouse liver. MG caused a small, not dose-related, increase in thyroid gland follicular adenomas and carcinomas, and of mammary gland carcinomas in female rats. LMG caused an increase in hepatocellular adenomas and carcinomas in female mice. Both MG and LMG may be considered as carcinogenic and as genotoxic in vivo. A lower 95% confidence limit for a benchmark response of 10% extra risk (BMDL10) of 13 mg/kg bw per day for hepatocellular adenomas and carcinomas was selected as reference point for neoplastic effects. For non-neoplastic effects, a lower 95% confidence limit for a benchmark response of 5% extra risk (BMDL05) of 6 mg/kg bw per day was selected for the effect of MG on liver weight and of LMG on body weight. The margins of exposure were 1.1 × 106 or greater for neoplastic effects and 4.9 × 105 or greater for non-neoplastic effects. The CONTAM Panel concluded that it is unlikely that exposure to food contaminated with MG/LMG at or below the RPA of 2 μg/kg represents a health concern.

Health risk from veterinary antimicrobial use in China's food animal production and its reduction

The overuse and misuse of veterinary drugs, particularly antimicrobials, in food animal production in China cause environmental pollution and wide food safety concerns, and pose public health risk with the selection of antimicrobial resistance (AMR) that can spread from animal populations to humans. Elevated abundance and diversity of antimicrobial resistance genes (ARGs) and resistant bacteria (including multi-drug resistant strains) in food-producing animals, food products of animal origin, microbiota of human gut, and environmental media impacted by intensive animal farming have been reported. To rein in drug use in food animal production and protect public health, the government made a total of 227 veterinary drugs, including 150 antimicrobial products, available only by prescription from licensed veterinarians for curing, controlling, and preventing animal diseases in March 2014. So far the regulatory ban on non-therapeutic use has failed to bring major changes to the long-standing practice of drug overuse and misuse in animal husbandry and aquaculture, and significant improvement in its implementation and enforcement is necessary. A range of measures, including improving access to veterinary services, strengthening supervision on veterinary drug production and distribution, increasing research and development efforts, and enhancing animal health management, are recommended to facilitate transition toward rational use of veterinary drugs, particularly antimicrobials, and to reduce the public health risk arising from AMR development in animal agriculture.

Occurrence of chloramphenicol in cereal straw in north-western Europe

ABSTRACTTwo surveys are presented of straw analysed for naturally occurring chloramphenicol (CAP), a drug banned for use in food-producing animals. In the first study, CAP was analysed by LC-MS/MS and detected in 37 out of 105 straw samples originating from the Netherlands, France, the UK, Germany and Denmark. The highest level found was 6.3 µg kg−1, the average 0.6 µg kg−1 and the median 0.2 µg kg−1. The second study included a method comparison between ELISA and LC-MS/MS and a survey of CAP in cereal straw sampled at farms in all areas of Sweden. A total of 215 samples were screened by ELISA and a subset of 26 samples was also analysed by LC-MS/MS. Fifty-four of the samples contained more than 1 µg kg−1 CAP and the highest level found was 32 µg kg−1 (confirmed by LC-MS/MS). The highest contents of CAP in this study were allocated to the Baltic sea coast in the south-eastern part of Sweden (the county of Skåne and the Baltic Sea isle of Gotland). These results indicate a high incidence of CAP in straw in north-west Europe and have a severe impact on the enforcement of European Union legislation.

Production of antisera to phenylbutazone and oxyphenylbutazone for use in immunochemical detection assays

ABSTRACTPhenylbutazone, a non-steroidal anti-inflammatory drug commonly used to treat horses for musculoskeletal disorders, can cause adverse effects in humans and is therefore not permitted for use in food-producing animals in the EU. In recent years some equine and bovine samples have been found to be non-compliant. While physicochemical methods of analysis exist there is a need for less-expensive, rapid screening methods such as immunoassays. This study describes the production of antisera to detect phenylbutazone and its main metabolite, oxyphenylbutazone. Four haptens were chosen for immunogen preparation and two of these, suxibuzone and γ-hydroxyphenylbutazone, produced antisera with 50% of maximal inhibitory concentration (IC50s) of <5 ng mL−1 for phenylbutazone. Antisera with IC50s of 5.5 ng mL−1 for phenylbutazone and 5.6 ng mL−1 for oxyphenylbutazone were produced by their respective haptens. The figures suggest that the antisera could deliver detection capabilities below the concentration that is recommended by the Community Reference Laboratory (5 ng mL−1).

Effect of colostrum replacer supplementation of milk replacer on the risk of antibiotic treatment and performance of pre-weaned dairy calves

Concerns over the risks of emergence of antibiotic-resistant bacteria due to excessive antibiotic use in food producing animals has led to increased restrictions of their use to treat and prevent common infectious diseases. Additionally, the absence of discovery and development of new antibiotics has prompted efforts to develop alternatives to antimicrobial use. Daily supplementation of milk replacer with immunoglobulins and immune factors from colostrum replacers could be an alternative prophylactic measure to decrease antibiotic usage in young dairy calves. The objective of this study was to evaluate the effect of colostrum supplementation of milk replacer on the risk of antibiotic treatment and weight gain of pre-weaned dairy calves.

Intermingled Klebsiella pneumoniae Populations Between Retail Meats and Human Urinary Tract Infections.

Klebsiella pneumoniae is a common colonizer of the gastrointestinal tract of humans, companion animals, and livestock. To better understand potential contributions of foodborne K. pneumoniae to human clinical infections, we compared K. pneumoniae isolates from retail meat products and human clinical specimens to assess their similarity based on antibiotic resistance, genetic relatedness, and virulence. Klebsiella pneumoniae was isolated from retail meats from Flagstaff grocery stores in 2012 and from urine and blood specimens from Flagstaff Medical Center in 2011-2012. Isolates underwent antibiotic susceptibility testing and whole-genome sequencing. Genetic relatedness of the isolates was assessed using multilocus sequence typing and phylogenetic analyses. Extraintestinal virulence of several closely related meat-source and urine isolates was assessed using a murine sepsis model. Meat-source isolates were significantly more likely to be multidrug resistant and resistant to tetracycline and gentamicin than clinical isolates. Four sequence types occurred among both meat-source and clinical isolates. Phylogenetic analyses confirmed close relationships among meat-source and clinical isolates. Isolates from both sources showed similar virulence in the mouse sepsis model. Meat-source K. pneumoniae isolates were more likely than clinical isolates to be antibiotic resistant, which could reflect selective pressures from antibiotic use in food-animal production. The close genetic relatedness of meat-source and clinical isolates, coupled with similarities in virulence, suggest that the barriers to transmission between these 2 sources are low. Taken together, our results suggest that retail meat is a potential vehicle for transmitting virulent, antibiotic-resistant K. pneumoniae from food animals to humans.

Scientific Opinion on nitrofurans and their metabolites in food

Nitrofurans are antimicrobial agents not authorised for use in food-producing animals in the European Union. Nitrofurans are rapidly metabolised, occurring in animal tissues as protein-bound metabolites. The European Commission requested EFSA to provide a scientific opinion on the risks to human health related to the presence of nitrofurans in food and whether a reference point for action (RPA) of 1.0 µg/kg for the marker metabolites is adequate to protect public health. Data on occurrence of nitrofuran marker metabolites in food were extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF). The CONTAM Panel concluded that these data were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which a single nitrofuran marker metabolite is present at 1.0 µg/kg in foods of animal origin, excluding milk and dairy products. The mean chronic dietary exposure for this worst-case scenario would range from 3.3 to 8.0 and 1.9 to 4.3 ng/kg b.w. per day for toddlers and adults, respectively. Nitrofurans and their marker metabolites, generally, are genotoxic and carcinogenic and, also, have non-neoplastic effects in animals. Margins of exposure (MOEs) were calculated at 2.0 × 105 or greater for carcinogenicity and at 2.5 × 103 or greater for non-neoplastic effects. The CONTAM Panel concluded that it is unlikely that exposure to food contaminated with nitrofuran marker metabolites at or below 1.0 µg/kg is a health concern. A scenario in which foods are considered to be contaminated with semicarbazide, from use of carrageenan as a food additive, at 1 µg/kg was used to assess whether it is appropriate to apply the RPA to foods of non-animal origin; MOEs of greater than 104 calculated for non-neoplastic effects do not indicate a health concern.

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk.

In recent years, increasing attention has been paid to the role of hormones in breast cancer etiology, following reports that heightened levels of endogenous hormones and exposure to exogenous hormones and other endocrine-disrupting chemicals through food and the environment are associated with increased breast cancer risk. Seven hormone drugs (testosterone propionate, trenbolone acetate, estradiol, zeranol, progesterone, melengestrol acetate, and bovine somatotropin) are approved by the U.S. Food and Drug Administration for use in food animals. There is concern that these drugs or their biologically active metabolites may accumulate in edible tissues, potentially increasing the risk of exposure for consumers. To date, the potential for human exposure to residues of these compounds in animal products, as well as the risks that may result from this exposure, is poorly understood. In this paper, we discuss the existing scientific evidence examining the toxicological significance of exposure to hormones used in food animal production in relation to breast cancer risk. Through a discussion of U.S. federal regulatory programs and the primary literature, we interpret the state of surveillance for residues of hormone drugs in animal products and discuss trends in meat consumption in relation to the potential for hormone exposure. Given the lack of chronic bioassays of oral toxicity of the seven hormone compounds in the public literature and the limitations of existing residue surveillance programs, it is not currently possible to provide a quantitative characterization of risks that result from the use of hormonal drugs in food animal production, complicating our understanding of the role of dietary hormone exposure in the population burden of breast cancer.

Antimicrobial Resistance and Plasmid Profiles of Campylobacter Species from Infants Presenting with Diarrhoea in Osun State, Nigeria

Antibiotic resistance among enteric bacterial pathogens complicates the heavy diarrhoea disease burden. Antimicrobial resistance of Campylobacter spp. to fluoroquinolones, which are generally used for the treatment of bacterial gastroenteritis, has increased during the past two decades, mainly as a result of the approval of this group of antimicrobials for use in food-producing animals. The aim is to determine the frequency of resistance of campylobacter to various antimicrobial agents and the relationship between antimicrobial agents of the isolates and the presence of plasmid. Twenty five Campylobacter isolates gotten from humans were subjected to antibiotics testing using Kirby Bauer disc diffusion method as well as standard E-test method. The plasmid profile of the isolates was determined using the Alkaline phosphatise procedure. The antimicrobial susceptibility testing of these isolates showed that all were sensitive to Erythromycin and Ciprofloxacin while none was sensitive to co-trimoxazole. The standard organisms were sensitive to co-trimoxazole (80%) and ciprofloxacin (65%) but were resistant to erythromycin (70%). No plasmid was found in streptomycin and ampicillin resistant strains, with the exception of four isolates which were co-trimoxazole-resistant and which contained around 24.4kb plasmids.

An Integrated Systems Approach is Needed to Ensure the Sustainability of Antibiotic Effectiveness for Both Humans and Animals.

The growing demand for animal products and the widespread use of antibiotics in bringing food animals to market have heightened concerns over cross-species transmission of drug resistance. Both the biology and emerging epidemiology strongly support the need for global coordination in stemming the generation and propagation of resistance, and the patchwork of global and country-level regulations still leaves significant gaps. More importantly, discussing such a framework opens the door to taking modular steps towards solving these challenges - for example, beginning among targeted parties rather than all countries, tying accountability to financial and technical support, or taxing antibiotic use in animals to deter low-value usage of these drugs. An international agreement would allow integrating surveillance data collection, monitoring and enforcement, research into antibiotic alternatives and more sustainable approaches to agriculture, technical assistance and capacity building, and financing under the umbrella of a One Health approach.

Current context of food safety in Vietnam: a glance at food of animal origin

Vietnam experiences a wet, tropical climate that encourages vector- and water-borne diseases. Official statistics of the Vietnam Food Administration point to microorganisms as the major cause of food poisoning outbreaks. This paper reviews the current situation of food safety in Vietnam focusing on microbial hazards of food from animal origin. Retail meat sample analyses (pork and chicken meat) showed high prevalence of Salmonella spp. in different regions including the main cities Hanoi and Ho Chi Minh. High levels of antimicrobial resistance are reported for pathogens in food-producing animals and raw foods sold on the market. Multidrug resistant Salmonella spp. to up to 12 different antibiotics has been found. Escherichia coli has also been reported as a significant reservoir of resistance and virulence genes in chicken and pork. Furthermore, resistance to chloramphenicol still occurs at high frequency in pig isolates and in aquaculture, although this drug has been banned from use in food-producing animals for a decade, suggesting a misuse of the antibiotic or a cross-resistance provided by the use of other antibiotics. From this point of view, strengthening the legal framework of the food safety and quality system in Vietnam is required to improve the surveillance of pathogens in food and to mitigate the antibiotic resistance. The integration of Vietnam into the World Trade Organisation in 2007 has fostered the development of food safety policy in the country. Based on the new food law issued in 2010, a national strategy for food safety was approved for the period 2011-2020.