Drugs In Food-producing Animals Research Articles

Quantifying trade-offs between therapeutic efficacy and resistance dissemination for enrofloxacin dose regimens in cattle

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\beta}$$\\end{document}), elimination of the drug from the colon (ϑ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\vartheta$$\\end{document}), fifty percent sensitive bacteria (P. multocida) killing effect (Ls50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{L}}_{\ ext{s50}}$$\\end{document}), fifty percent of bacteria (E. coli) above ECOFF killing effect (Cr50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{C}}_{\ ext{r50}}$$\\end{document}), and net drug transfer rate in the lung (γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}) parameters.

Analytical Cross-sectional Study on the Knowledge, Attitudes, and Practices on Antimicrobial Use and Resistance among Backyard Swine Raisers in Baybay City, Philippines

Antimicrobial resistance (AMR) is a global health concern, wherein microorganisms become resistant to antimicrobial drugs used in the treatment of human diseases and is linked to the misuse and overuse of antimicrobial drugs in food-producing animals. This study aimed to assess the knowledge, attitudes, and practices (KAP) of backyard swine raisers in Baybay City, Leyte, the Philippines, toward antimicrobial drugs and usage in the context of AMR. Data were gathered from 303 randomly selected backyard swine raisers in 28 villages of Baybay City through in-depth interviews. KAP levels were determined by performing descriptive statistics. Predictors and associated variables were analyzed through univariable and multivariable regression analyses. The majority of the respondents have poor to moderate knowledge (98.68%), moderate attitudes (68.65%), and poor practices (82.18%) on the use of antimicrobials. Attainment of a college degree (adjusted β = 1.32, p = 0.0021) was significantly associated with the respondents' knowledge. Meanwhile, the respondents’ attitude levels were positively associated with vocational (adjusted β = 4.84, p = 0.0004) and college education (adjusted β = 2.11, p = 0.0444). Overall, the educational attainment (college: adjusted β = 1.58, p = 0.0068), the knowledge mean (β = 5.25, p < 0.0001), and the attitude mean (β = 1.11, p < 0.0001) significantly influenced the respondents’ practices on antimicrobial use. Education is crucial in improving the farmers' KAP regarding the use of antimicrobials. To help prevent the furtherance of AMR, it is essential for government agencies to enhance the farmers’ KAP levels by conducting training on antimicrobial use and facilitating AMR awareness seminars.

Evaluation of Antibiotics Residues in Milk and Meat Using Different Analytical Methods.

Veterinary drugs are pharmacologically and biologically active chemical agents. At present, veterinary drugs are extensively used to prevent and treat animal diseases, to promote animal growth, and to improve the conversion rate of feed. However, the use of veterinary drugs in food-producing animals may leave residues of the parent compounds and/or their metabolites in food products resulting in harmful effects on humans. To ensure food safety, sensitive and effective analytical methods have been developing rapidly. This review describes sample extraction and cleanup methods, and different analytical techniques are used for the determination of veterinary drug residues in milk and meat. Sample extraction methods, such as solvent extraction, liquid-liquid extraction, and cleanup methods such as dispersive solid-phase extraction and immunoaffinity chromatography, were summarized. Different types of analytical methods such as microbial, immunological, biosensor, thin layer chromatography, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry were discussed for the analysis of veterinary drug residues in animal-derived foods. Liquid chromatography-tandem mass spectrometry is the most widely used analytical technique for the determination of antibiotic drug residues. This is due to the powerful separation of LC and accurate identification of MS, and LC-MS/MS is more popular in the analysis of veterinary drug residues.

REVIEW ON THE IMPACTS OF DRUG RESIDUE IN ANIMALS PRODUCT ON HUMANS HEALTH ISSUES

The use of veterinary drugs in food-producing animals may result in drug residues in foodstuffs such as meat, milk, eggs, or honey. High degree of antibiotics residues consumption from animal products to human might affect immunological reactions and can unfavourably influence digestive microbiota in susceptible people. Antimicrobials also known as antibiotics, anti-infectives, antibacterials or chemotherapeutics, include synthetic and natural compounds. The introduction of antibiotics to the veterinary field started soon after the use of antibiotics for the treatment of bacterial diseases in humans. Detection of drug residues from tissues and other animal products could be quite an expensive, time consuming and laborious venture. To determine the withdrawal period, regulatory authorities must employ a scientific process that includes establishing the Maximum Residue Limit for that medicine. The growing use of antimicrobials to prevent and treat diseases, increases the probability of residues of these substances in products obtained from animals. Resistant microorganism can get access to human, either through direct contact or indirectly via milk, meat, and or egg. The ongoing threat of antibiotic contamination is one of the biggest challenges to public health that is faced not only by the African people, but also by the human population worldwide. Globally, more than half of all medicines are prescribed, dispensed or sold improperly. The first step in residue prevention is to make individuals and organizations aware of the problem through education by means of scientific literature, computer databases, veterinary consultations and the efforts of national organizations.

Professor Susanne Rath, a researcher who has bravely faced challenges since childhood, kindly granted BrJAC an interview

Susanne Rath is an associate professor in the Institute of Chemistry at the University of Campinas (Unicamp), where she coordinates the “Laboratório de Bioanalítica Paracelsus”. She graduated with a Bachelor's degree in Chemistry (1983) from the University of Brasília (UnB), a Master’s degree in Chemistry (1986) from Unicamp, and a Ph.D in Pharmaceutical Chemistry (1990) from the Johann Wolfgang Goethe Universität Frankfurt am Main, Germany. So far, she has published 110 articles and seven book chapters, had four patents granted, and she has presented over 230 papers at scientific conferences. She supervised 17 master's students, 20 doctorate students and 10 post-docs. In addition, she coordinated 23 research projects supported by Brazilian funding agencies. Prof. Dr. Rath’s primary research is focused on toxic compounds in food, residue depletion studies of veterinary drugs in food-producing animals, development and validation of analytical methods, application of bidimensional chromatography and mass spectrometry, environmental impact assessment of veterinary drugs, antimicrobial resistance and N-nitrosamines in food, cosmetics and drugs. Since 2007, Prof. Rath has been a member of the Joint Expert Committee on Food Additives (JECFA) of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). Since 2011, Prof. Rath has been a member of the Technical Group on Maximum Residue Limits for Veterinary Drugs in Food of the National Health Surveillance Agency (Anvisa) of the Ministry of Health of Brazil.

Prevalence and Characterization of PVL-Positive Staphylococcus aureus Isolated from Raw Cow's Milk.

The present study aimed to investigate the prevalence, antibiotic susceptibility profiles, and some toxin genes of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (S. aureus) in unpasteurized raw cow’s milk collected from retail outlets located at Mansoura, Dakahliya governorate, Egypt. In that context, a total of 700 raw cow’s milk samples were investigated for the presence of S. aureus, which was identified in 41.1% (288/700) of the samples. Among the S. aureus isolates, 113 PVL-positive S. aureus were identified and subjected for further analysis. The PVL-positive S. aureus were investigated for the existence of toxin-related genes, including hemolysin (hla), toxic shock syndrome toxin-1 (tst), and enterotoxins (sea, seb, sec, see, seg, sei, and selj). Genotypic resistance of PVL-positive strains was performed for the detection of blaZ and mecA genes. Among the PVL-positive S. aureus, sea, seb, and sec were detected in 44.2, 6.2%, and 0.9%, respectively, while the hla and tst genes were identified in 54.9% and 0.9%, respectively. The blaZ and mecA genes were successfully identified in 84.9 (96/113) and 32.7% (37/113) of the total evaluated S. aureus isolates, respectively. PVL-positive S. aureus displayed a high level of resistance to penicillin, ampicillin, and trimethoprim-sulfamethoxazole. Multidrug resistance (resistant to ≥3 antimicrobial classes) was displayed by all methicillin-resistant S. aureus (MRSA) and 38.2% of methicillin-sensitive S. aureus (MSSA) isolates. The obtained findings are raising the alarm of virulent PVL-positive MRSA clones in retail milk in Egypt, suggesting the requirement for limiting the use of β-lactam drugs in food-producing animals and the importance of implementing strong hygiene procedures in dairy farms and processing plants.

Omics applications in the fight against abuse of anabolic substances in cattle: challenges, perspectives and opportunities

• Omics techniques can identify biomarkers for untargeted screening of growth promoter . • Advanced statistics can help to overcome some limitations of current omics workflows. • Implementation in current legislation of relevant omics-technologies is recommended. • Multi-omics data fusion approaches will play a major role in animal science. Omics techniques, already applied into several topics of animal science, are considered useful tools in the fight against abuse of prohibited drugs in food producing animals: indeed, transcriptomics, proteomics, and metabolomics seem to be the most relevant untargeted applications to overcome limitations of the conventional analytical targeted approach. Such limitations, often related to use of novel designer drugs and/or rapid elimination of drugs residues from blood, urine, milk and other animal tissues, usually does not affect induced biological alterations in treated animals. Omics sciences represent therefore an alternative diagnostic approach for untargeted screening of growth promoters’ abuse. The most relevant biomarkers-based approaches are reported in the present review on domestic cattle.

Ethnoveterinary for food-producing animals and related food safety issues: A comprehensive overview about terpenes.

Alternatives to the use of conventional veterinary drugs in food-producing animals have gained attention, such as the use of natural products (NPs), mainly to soften the risks to the animal, the environment, and consumer's health. Although NPs have consistent advantages over conventional drugs, they cannot be considered risk free under food safety matters. In this way, this document presents a comprehensive overview of the importance of considering both the pharmacological and toxicological properties of the constituents of a NP from plants intending the standardization and regulation of its use in food-producing animals. Terpenes are the most diverse class of natural substances present in NP of vegetal origin with a broad range of biological activities that can be explored in veterinary science; however, certain plants and terpenes also have significant toxic effects, a fact that can harm the health of animals and consequently generate economic losses and risks for humans. In this context, this review gathered scientific data of vegetal species of importance to ethnoveterinary for food-producing animals, which produce terpenes, its biological effects, and their implications on food safety issues for consumers. For this, more than 300 documents were selected from different online scientific databases. The present data and discussion may contribute to the rational commercial exploration of this class of NPs in veterinary medicine.

Nutritional Supplements Containing Cardus mariano, Eucalyptus globulus, Gentiana lutea, Urtica urens, and Mallotus philippinensis Extracts Are Effective in Reducing Egg Shedding in Dairy Jennies (Equus asinus) Naturally Infected by Cyathostomins.

The increasing levels of anthelmintic resistance together with the restrictions in the use of drugs in food producing animals have enforced the search for sustainable alternative approaches for parasite control. The current study aimed to investigate the safety and the efficacy of a commercially available phytotherapic formulation against gastrointestinal strongyles in donkeys. Twenty-two Ragusana jennies (2.6 ± 0.5 years old) were assigned to two equal groups. One group was treated with two doses of a phytotherapic supplement Paraxitebio® containing Cardus mariano, Eucalyptus globulus, Gentiana lutea, Urtica urens, and Mallotus philippinensis, 14 days apart (Group A). One group was used as negative control (Group B). Individual fecal samples were collected at the beginning of the study (T−1), and after 7, 14, and 28 days (T7, T14, T28). Blood samples were collected on T−1 and T28 in order to assess changes in donkeys' hematological profile. After the initial rise in EPG values observed on T7, Group A showed a significant EPG decrease with lower eggs per gram (EPG) count compared to Group B on T28 and an overall fecal egg count reduction of 56.9% on the same time-point. Hematological parameters were within the normal physiological ranges for enrolled donkeys. However, significant differences in the values of RBCs, Hb, MCHC, MCV, WBCs, eosinophils, and basophils were recorded between groups after phytotherapic treatments, with Group A showing a general improvement in the hemogram picture. The phytotherapic supplement used in the current study was helpful in controlling intestinal parasites allowing a significant reduction in the fecal egg count 28 days after treatment. Further studies are needed to better explore the specific mode of action of the plant-derived formulation herein tested as well as to encourage their use as tool for the control of equine strongylosis under multimodal integrated approach in dairy donkey farms.

Determination of veterinary drug residues in food of animal origin: Sample preparation methods and analytical techniques

Veterinary drugs are widely used in animal husbandry to prevent and treat animal diseases, to promote animal growth, and to improve the conversion rate of feed. However, the use of veterinary drugs in food-producing animals may leave residues of the parent compounds, and/or their metabolites in food products resulting in harmful effects to humans. To ensure food safety, sensitive and effective analytical methods have been developing rapidly. So it is necessary to make a systematic summary of detection methods of veterinary drug residues. Sample preparation methods and analytical techniques are the two main parts of analyzing veterinary drug residues which were described in detail. Sample preparation methods, such as solid-phase extraction, liquid–liquid extraction, immunoaffinity chromatography, and QuEChERS, were summarized by the specific examples. The three types of methods, microbial, immunological, and physicochemical methods, for screening or determination were described, including microbial inhibition, enzyme-linked immunosorbent assay, colloidal gold immunoassay, fluorescence polarization immunoassay, biosensor technology, application of quantum dots, capillary electrophoresis, liquid chromatography, and liquid chromatography-mass spectrometry. In addition, the advantages and shortcomings of methods were also described. The challenges and prospects were discussed for the analysis of veterinary drug residues in animal-derived foods.

Antimicrobial drug residues in animal-derived foods: Potential impact on the human intestinal microbiome.

The use of veterinary drugs in food-producing animals may result in the presence of low levels of drug residues in these edible, animal-derived foods, with potential dietary exposure to humans. Since therapeutic doses of antibiotics have been shown to affect bacterial populations in the gastrointestinal tract microbiome and can also promote the emergence of antibiotic-resistant bacteria, there is concern that animal drugs at residue level concentrations could also perturb the intestinal microbiome composition and modify the antimicrobial resistance profile of the human intestinal microbiota. This review provides updated information on the VICH GL#36(R2), on evaluating the safety of veterinary drug residues in animal-derived foods and their effects on the human intestinal microbiome; discusses critical research knowledge gaps and challenges in evaluating the impact of drug residues in animal-derived foods on the human intestinal microbiome; and analyzes integrated basic and applied research approaches, currently being conducted at FDA, on studies that specifically address key regulatory science questions. Moreover, this review aims to emphasize future research needs on scientific methodology and provides general recommendations on drug inactivation, bioavailability, and antimicrobial resistance, to improve the safety evaluation and risk assessment of antimicrobial residues and their impact on the gastrointestinal microbiota, with the goal of ensuring food safety.

Cross-sectional Assesses on Irrational Use of Veterinary Drugs in Adami Tulu Jiddo Kombolcha Distrct, East Shoa Zone, Oromia Regional State, Ethiopia

A cross-sectional study was conducted from November 2014 to March, 2015 at Adami-Tulu Jiddo kombolcha district in five peasant association and four towns to assess the irrational use of veterinary drugs in food producing animals and assess the factors those leads to irrational uses of veterinary drugs from farmers, veterinary clinicians and private veterinary pharmacists’ side. Out of 60 farmers interviewed, 55 (91.7%) of them uses veterinary drugs. From these 55 respondents, 44 (80%) of them treat their animals by presenting to the clinic and 11 (20%) of them treat by themselves at home with veterinary drugs. There was statistically significant association (P<0.05) between source of a drug and response of the disease to treatment. Of the total 60 farmers, 18 (30%) uses black market, 22 (36.7%) uses veterinary pharmacy and 20 (33.3%) uses veterinary clinic as a source of drugs. Among these 17 (94.4%), 2 (9.1%) and 3 (15%) of them responded as these sources of drugs have no response to treatment from the black market, veterinary pharmacy and veterinary clinic respectively. Regarding with drug regulation problem 7 (70%) of the farmers responded as there were lack of veterinary drug supply and lack of veterinary supervision. In line with clinicians, of the total 10 interviewed, 2 (20%) of them responded as the farmers reject their advice on animals’ treatment approach and 10% of the clinicians depend on the farmers’ needs on the way they use the drugs. In line with drug availability and its effectivity related issues, 8 (80%) of clinicians responded as there was no sufficient drug availability and no effective drug for the specific disease. On the other hand from 10 private veterinary pharmacists interviewed, 7 (70%) of them sell drugs without prescription. Generally irrational use of veterinary drugs is a common problem in developing countries where resource and educated human power are not access as wanted. Hence, growing awareness in the community about the rational use of veterinary drugs and controlling the illegal contraband of it were recommended as the main measures to alleviate the expansion of irrational use of vet drugs.

Assessment of antimicrobial drug administration and antimicrobial residues in food animals in Enugu State, Nigeria

Imprudent administration of antimicrobial drugs in food-producing animals can facilitate the development and spread of antimicrobial-resistant organisms and also enhance the occurrence of antimicrobial residue in animal products. This study was undertaken to assess antimicrobial drug administration to food animals in livestock farms in Enugu State and determine livestock farmers' awareness on the consequences of imprudent antimicrobial administration to food animals and finally the prevalence of antimicrobial drug residues in edible tissues of cattle and pigs in the state. Structured questionnaire was used to extract information on antimicrobial drug administration and consequences of irresponsible use of antimicrobials in food animals from 109 livestock farms/farmers randomly selected using multi-stage sampling technique. Premi® test technology (R-Biopharm, Germany) was used to screen for antimicrobial residues in edible tissues from 300 carcasses consisting of 165 cattle and 135 pigs slaughtered for human consumption in two major slaughterhouses in Enugu State. Tetracyclines (90.8%), penicillins and beta-lactams (89.9%), and aminoglycoside (57.8%) were the classes of antimicrobials most frequently administered to food animals in the farms surveyed. Withdrawal period was not observed in 65% of the farms. About 30% of cattle and 23% of pig carcasses screened contained detectable amounts of antimicrobial residues. There is widespread indiscriminate administration of antimicrobial drugs in food animals in Enugu State. This underscores the need for public enlightenment on prudent use of antimicrobial drugs in food-producing animals in order to preserve the therapeutic efficacy for sustainable livestock production and to safeguard human health.

Overexpression of biologically safe Rorippa indica defensin enhances aphid tolerance in Brassica juncea.

Transgenic mustard plants ( Brassica juncea ) expressing non-allergenic and biologically safe RiD peptide show higher tolerance against Lipaphis erysimi. Rorippa indica defensin (RiD) has previously been reported as a novel insecticidal protein derived from a wild crucifer Rorippa indica. RiD was found to have an effective insecticidal property against mustard aphid, Lipaphis erysimi. In the present study, RiD was highly upregulated in R. indica during aphid infestation initiating a defense system mediated by jasmonic acid (JA), but not by salicylic acid (SA)/abscisic acid (ABA). RiD has also been assessed for biosafety according to the FAO/WHO guideline (allergenicity of genetically modified foods; Food And Agriculture Organisation of the United Nations, Rome, Italy, 2001) and Codex Alimentarius Guideline (Guidelines for the design and implementation of national regulatory food safety assurance programme associated with the use of veterinary drugs in food producing animals. Codex Alimentarius Commission. GL, pp 71-2009, 2009). The purified protein was used to sensitize BALB/c mice and they showed normal histopathology of lung and no elevated IgE level in their sera. As the protein was found to be biologically safe and non-allergenic, it was used to develop transgenic Brassica juncea plants with enhanced aphid tolerance, which is one of the most important oilseed crops and is mostly affected by the devastating pest-L. erysimi. The transgene integration was monitored by Southern hybridization, and the positive B. juncea lines were further analyzed by Western blot, ELISA, immunohistolocalization assays and in planta insect bioassay. Transgenic plants expressing RiD conferred a higher level of tolerance against L. erysimi. All these results demonstrated that RiD is a novel, biologically safe, effective insecticidal agent and B. juncea plants expressing RiD are important components of integrated pest management.

Biochemical proximates of pumpkin (Cucurbitaeae spp.) and their beneficial effects on the general well-being of poultry species.

There is a growing need to increase productivity in poultry. Growth hormones and antibiotics have the ability to improve health, weight gain and feed efficiency in meat-producing animals. The growth-promoting antibiotics are administered to poultry to improve the general performance of the chicken. However, the use of the xenobiotic drugs in food-producing animals has been a concern and a sensitive issue of debate for several decades in the EU and many other regional blocks of the world. Consequently, the use of hormones in animal production has been banned in Italy, Denmark and Germany for over 4-5 decades, while Belgium and Greece had never permitted its use for livestock fattening purposes. Bioactive phytochemicals exhibit antimicrobial, antioxidant, antiparasitic, antiprotozoal, antifungal and anti-inflammatory properties and consequently have several beneficial effects on appetite, growth and the immune status of the animal. In South Africa, different species of pumpkin are produced for food due to their high nutrient content. The flesh serves as a traditional food, while the seeds and peels are commonly discarded. Pumpkin seed extract is reported to be useful for immunomodulation, reproductive health, therapeutics over a wide range of disease conditions and stimulates metabolism of accumulated fats. Studies have also shown that pumpkin seeds are a valuable source of protein and fat. Their complexity and extent of bioactivity offers sustainable prospects for natural control of pathogenic/parasitic organisms, stimulate nutrition or enhance resistance to disease infections, and reduce abdominal fat and serum levels of harmful lipids, while increasing serum levels of beneficial lipids.

Tissue distribution of sulphadimidine sodium in non-starved and starved grower turkeys (meleagris gallopavo)

Background: The use of veterinary drugs in food-producing animals has potential to generate residues in edible tissues and posses health hazard to consumers especially when the withdrawal period is not observed.Objectives: The study was conducted to determine the tissue residue and withdrawal period of sulphadimidine in non-starved and starved grower turkeys following a single intramuscular administration.Methods: Forty two turkeys of both sexes and 12 weeks old weighing 1.57±0.2 kg were divided into two groups of twenty one each. One group was administered a single intramuscular dose of sulphadimidine sodium (100mg/kg body weight). The other group was kept off-feed for 48 hours before drug administration. Three turkeys each were sacrificed from the starved and non-starved group and two grammes (2g) of tissue sample were harvested from selected tissues.Results: The results showed that the drug residues persisted in all the tissues of turkeys sampled for up to thirty (30) days after drug administration. The starved turkeys maintained consistently higher concentrations of the drug in the tissues than fed ones. Sulphadimidine residue was significantly increased (p&lt;0.05) between days 3 to 6 in the spleen of non-starved turkeys. However, the concentrations in the spleen decreased significantly (p&lt;0.05) between days 6 to 10 and 25 to 30.Conclusion: Sulphadimidine residue persisted in the tissues of non-starved and starved turkeys for up to 30 days after intramuscular injection. This should be given due consideration in the estimation of the withdrawal period for the drug, since sulphadimidine residue in meat &gt; 0.2 ppm is unsafe for human consumption.

An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd.

Qualitative screening of veterinary anti-microbial agents in tissues, milk, and eggs of food-producing animals using liquid chromatography coupled with tandem mass spectrometry.

A method for the analysis of 120 drugs in animal derived food was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These analytes belong to 12 families of veterinary anti-microbial agents (quinolones, macrolides, β-lactams, nitroimidazoles, sulfonamides, lincomycines, chloramphenicols, quinoxalines, tetracyclines, polypeptides, and antibacterial synergists) as well as other compounds not assigned to a particular drug family. The animal derived food samples include muscle and liver of swine, bovine, sheep, and chicken, as well as hen eggs and dairy milk. The sample preparation included ultrasound-assisted extraction (UAE) with acetonitrile-water and a final clean-up with auto solid-phase extraction (SPE) on HLB cartridges. The detection and quantification of 120 anti-microbial agents was performed using LC-MS/MS in positive and negative ion mode. The chromatographic separation was performed on a C18 column using acetonitrile and 0.1% formic acid as the mobile phase. The limit of detection (LOD) and limit of quantification (LOQ) of all drugs in food-producing animals were 0.5-3.0μg/kg and 1.5-10.0μg/kg, respectively. The developed method was successfully utilized to monitor real samples, which demonstrated that it is a simple, fast, and robust method, and could be used as a regulatory to screen for the presence of residues from veterinary anti-microbial drugs in animal-derived foods.

Radiolabeled metabolite and disposition studies in support of safety assessment.

BioanalysisVol. 7, No. 5 CommentaryRadiolabeled metabolite and disposition studies in support of safety assessmentAshley Beattie, Stephen Madden, Chris Lowrie & David MacPhersonAshley BeattieAuthor for correspondence: E-mail Address: ashley.beattie@crl.comDepartment of Environmental Sciences, Charles River, Edinburgh, EH33 2NE, UKSearch for more papers by this author, Stephen MaddenDepartment of Metabolism & Pharmacokinetics, Preclinical Services, Charles River, Edinburgh, EH33 2NE, UKSearch for more papers by this author, Chris LowrieDepartment of Environmental Sciences, Charles River, Edinburgh, EH33 2NE, UKSearch for more papers by this author & David MacPhersonDepartment of Chemistry, Charles River, Edinburgh, EH33 2NE, UKSearch for more papers by this authorPublished Online:31 Mar 2015https://doi.org/10.4155/bio.15.18AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: distributionexposuremass spectrometrymetabolismradiochromatographysafety assessmentReferences1 ICH M3 (R2) – Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. (2008) www.ema.europa.eu/docs Google Scholar2 Pellegatti M. The debate on animal ADME studies in drug development: an update. Expert Opin. Drug Metabol. Toxicol. 11(1), 1615–1620 (2014).Crossref, Google Scholar3 Obach RS, Nedderman AN, Smith DA. Radiolabelled mass-balance excretion and metabolism studies in laboratory animals: are they still necessary? Xenobiotica 42, 46–46 (2012).Crossref, Medline, CAS, Google Scholar4 White RE, Evans DC, Hop CE et al. Radiolabelled mass-balance excretion and metabolism studies in laboratory animals: a commentary on why they are still necessary. Xenobiotica 43, 219–425 (2013).Crossref, Medline, CAS, Google Scholar5 Nedderman AN, Dear GJ, North S et al. From definition to implementation: a cross-industry perspective of past, current and future MIST strategies. Xenobiotica 41(8), 605–622 (2011).Crossref, Medline, CAS, Google Scholar6 OECD. Test No. 503: Metabolism in Livestock (Section 5). In: OECD Guidelines for the Testing of Chemicals. OECD Publishing, Paris, France (2007). www.oecd-ilibrary.orgGoogle Scholar7 EPA. Residue chemistry test guidelines, OPPTS 860. In: 1340 Residue Analytical Method, EPA Publishing, Washington, DC, USA (1996). www.epa.govGoogle Scholar8 VICH GL46 Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-producing Animals: Metabolism Study to Determine the Quantity and Identify the Nature of Residues. (2012) www.fda.gov Google Scholar9 Regulations (EC) No 1107/2009 of the European Parliament and of the Council (2009). http://eur-lex.europa.eu/LexUriServGoogle ScholarFiguresReferencesRelatedDetailsCited ByDeuterium- und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften4 January 2018 | Angewandte Chemie, Vol. 130, No. 7Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences4 January 2018 | Angewandte Chemie International Edition, Vol. 57, No. 7Themed Issue on Radioisotopic BioanalysisMark Seymour31 March 2015 | Bioanalysis, Vol. 7, No. 5 Vol. 7, No. 5 Follow us on social media for the latest updates Metrics Downloaded 149 times History Published online 31 March 2015 Published in print March 2015 Information© Future Science LtdKeywordsdistributionexposuremass spectrometrymetabolismradiochromatographysafety assessmentFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Veterinary Drug Residues in Food-animal Products: Its Risk Factors and Potential Effects on Public Health

The use of veterinary drugs in food-producing animals has the potential to generate residues in animal derived products (meat, milk, eggs and honey) and poses a health hazard to the consumer. There are many factors influencing the occurrence of residues in animal products such as drug’s properties and their pharmacokinetic characteristics, physicochemical or biological processes of animals and their products. The most likely reason for drug residues might be due to improper drug usage and failure to keep the withdrawal period. The major public health significances of drug residue are development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, and disruption of intestinal normal flora. The residual amount ingested is in small amounts and not necessarily toxic. However, there is limited information on the magnitude of veterinary drug residue worldwide. Hence, an extensive work has to be carried out to determine the magnitude of the problem, to prevent the occurrence of veterinary drug residues, and to familiarize all animal health professionals with the knowledge of pharmacokinetics, pharmacodynamics and toxicological effects of veterinary drugs to minimize the potential public health hazards due to drug residues in food of animal origin.