Use Of Drugs In Food Animals Research Articles

Association between automatic milking system parameters and intramammary infections in dairy cows at dry-off

IntroductionThe current global concern over increasing antimicrobial resistance among animal and human pathogens has motivated efforts to reduce antimicrobial drug use in food animals and its impact on antimicrobial resistance. One such strategy is to use selective dry cow therapy (SDCT) in dairy cows, which involves treating only cows with intramammary infection (IMI) at dry-off. However, efficient methods are needed to identify cows with IMI at dry-off to implement SDCT. Automatic Milking Systems (AMS) data may help farmers identify cows with IMI when individual Somatic Cell Count (SCC) is not routinely tested. This study assessed the correlation between cow-level and quarter-level AMS parameters and IMI at dry-off.Methods & ResultsA total of 733 udder quarters (comprising both Primiparous [PRIM] and Multiparous [MULT] cows) were sampled and categorized for IMI based on bacterial growth and SCC. Data were aggregated both daily and into 7-day and 15-day intervals preceding dry-off. The quarter-level prevalence of bacterial growth at dry-off was 24.28% overall. When stratified by parity, logistic regression analysis at 15 days to dry-off revealed that the average difference in mastitis detection index (MDi) in PRIM, MDi, and standard deviation milk flow rate in MULT were associated with increased odds of IMI at dry-off. Similarly, data from 7 days to dry-off revealed that average peak milk flow rate in PRIM, and MDi in MULT were associated with increased odds of IMI at dry-off. However, an increase in average milk yield was associated with decreased odds of IMI.Discussion & ConclusionOur findings underscore the significance of MDi, milk flow rate, peak milk flow rate, and milk yield in predicting IMI at dry-off. Notably, stronger associations were observed with data collected 7 days preceding dry-off. Further research is warranted to refine and validate algorithms amalgamating these variables for precise IMI prediction in cows at dry-off.

A Review on Veterinary Drug Management, Handling, Utilization and Its Resistance Side Effects

Veterinary drugs play an important role in the control and prevention of animal diseases and animal sufferings, however it have the potential to cause harm if it is not used properly. Successful animal health service provision needs the availability of safe, effective and affordable drugs of the required quality and quantity. The available drugs must be prescribed, presented, transported, dispensed, labeled, packaged, measured and used rationally. Rational use of drugs in veterinary medicine has manifold significance; it can be either public health significance, improve food safety concern, reduce the development of drug resistance and residue or economic significance; the need to rely on more expensive drugs and international trade barrier. The potential public health hazard as a result of irrational drug use in food animals includes limited efficacy, increase risk of unwanted effects such as the emergence of drug resistance and drug residue, waste of resources and psychosocial impacts. Irrational drug using is characterized by over-prescription, inappropriate dosage, incorrect duration and unnecessary risk. There are several reasons which may contribute to irrational use of drugs. Some of them are lack of information, inadequate training and education of graduates of veterinary medicine, poor communication between veterinarian and owner, lack of diagnostic facilities, demand from the animal owner, and promotional activities of pharmaceutical industries. This paper had induced to document and aware procedures and necessary activities to have rational drug use, and it would helps to have proper drug measurement and dose calculation as well as it tell us about 0drug resistance and its public health effects. Over all This review hoped that as it would be help to animal health professionals and enhance the quality of veterinary pharmaceutical services so that decrease the economic loss and public health hazard due to diseases of livestock and protects the impacts of drug resistance and its residue.

Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration.

Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.

Automation and applications of the tolerance limit method in estimating meat withdrawal periods for veterinary drugs

A program was written in R to facilitate the implementation of the tolerance limit method (TLM) for establishing regulatory withdrawal times for limiting drug residues in meat, milk, and eggs. The developed computer source code can use pharmacokinetic and regulatory data to calculate the drug withdrawal period according to United States Food and Drug Administration (U.S. FDA) guidelines. The code called the “Withdrawal Time Calculator (WTC)” applied this TLM method to meat samples. The program was tested with the data provided by the U.S. FDA guidance and other published data collected from in vivo studies. Additional algorithm validation data were flunixin and sulfamethazine liver concentration data from peer-reviewed publications generated by our laboratory. This manuscript reports the withdrawal period results from testing the developed WTC code. Moreover, the source code for the WTC contains a data removal algorithm, constructed according to U.S. FDA data elimination recommendations if the user chooses. The power of the WTC is that it bypasses the use of multiple platforms typically required to perform the TLM, including standard commercial spreadsheet software (i.e., Microsoft Excel) and Statistical Analysis System (SAS) while providing speed and usability. This novel program provides a platform to calculate a withdrawal period recommendation for any drug in any class of animal for various regulatory body standards and could be very helpful in cases of extra-label drug use in food animals.

Exploring Post-Treatment Reversion of Antimicrobial Resistance in Enteric Bacteria of Food Animals as a Resistance Mitigation Strategy.

Antimicrobial drug use in food animals is associated with an elevation in relative abundance of bacteria resistant to the drug among the animal enteric bacteria. Some of these bacteria are potential foodborne pathogens. Evidence suggests that at least in the enteric nontype-specific Escherichia coli, after treatment the resistance abundance reverts to the background pre-treatment levels, without further interventions. We hypothesize that it is possible to define the distribution of the time period after treatment within which resistance to the administered drug, and possibly other drugs in case of coselection, in fecal bacteria of the treated animals returns to the background pre-treatment levels. Furthermore, it is possible that a novel resistance mitigation strategy for microbiological food safety could be developed based on this resistance reversion phenomenon. The strategy would be conceptually similar to existing antimicrobial drug withdrawal periods, which is a well-established and accepted mitigation strategy for avoiding violative drug residues in the edible products from the treated animals. For developing resistance-relevant withdrawals, a mathematical framework can be used to join the necessary pharmacological, microbiological, and animal production components to project the distributions of the post-treatment resistance reversion periods in the production animal populations for major antimicrobial drug classes in use. The framework can also help guide design of empirical studies into the resistance-relevant withdrawal periods and development of mitigation approaches to reduce the treatment-associated elevation of resistance in animal enteric bacteria. We outline this framework, schematically and through exemplar equations, and how its components could be formulated.

Review of AMDUCA and Extra-Label Drug Use in Food Animals

This presentation will review the Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994 and how the Food Animal Residue Avoidance Databank (FARAD) provides scientifically-based residue withholding information within the context of extra-label drug use guidelines. Several beef and dairy cases will be presented to demonstrate FARAD’s successes and challenges to minimize violative drug residues in animal-derived food products. Finally, several of the research initiatives developed by FARAD scientists that have improved withdrawal time estimation will be reviewed within the context of extra-label drug use in food animals.

ResistantSalmonellaVirchow in Quail Products

To the Editor: Salmonella spp. resistant to multiple antimicrobial agents have emerged worldwide in recent years, but clinical relevance varies with the agent to which resistance evolves. Fluoroquinolones are often the drug of choice to treat gastrointestinal infections in humans, and resistance to this class of antimicrobial agents is associated with increased illness and death (1). Resistance to fluoroquinolones has emerged worldwide during the last decade. Salmonella isolates resistant to oxyiminocephalosporins because they produce extended-spectrum β-lactamases (ESBLs) have emerged worldwide since 1992. This emergence has caused concern since cephalosporins are drugs of choice to treat salmonellosis in children, to whom fluoroquinolones must not be administered because of toxicity issues. In Denmark, the first ESBL-producing isolate of animal origin from a Salmonella enterica serovar Heidelberg isolated from a boar imported from Canada in 2003 was reported (2), but such isolates have not previously been reported in food products. On October 15, 2003, the Danish Institute for Veterinary Research, the national reference laboratory, received 3 Salmonella isolates found in quails imported from France. Salmonella isolates found at any importer's laboratory in Denmark are submitted to the reference laboratory for further analyses. The quails were in the importer's storage room at the time of sampling; sampling was performed routinely by the importer's own laboratory. At the reference laboratory, the isolates were serotyped as S. enterica serovar Virchow and found resistant to ampicillin, ceftiofur, cephalothin, nalidixic acid, and tetracycline and with reduced susceptibility to ciprofloxacin (MICs >0.125 μg/mL) (3). Polymerase chain reaction detection and sequencing (4) showed that the β-lactam resistance was mediated by blaCTX-M-9. Pulsed-field gel electrophoresis was performed by using XbaI and BlnI as restriction enzymes according to the PulseNet protocol (5), and all 3 isolates had the same profile. On October 23, the importer was informed of the laboratory's findings and the increased risk associated with salmonella isolates simultaneously resistant to quinolones and cephalosporins. Based on this information, the importer withdrew the product from the supermarkets on October 24. Recently, S. enterica Virchow with blaCTX-M-9 has also been reported in poultry, poultry products, and humans in France (6), as well as humans in Spain (7) and the United Kingdom (8). The isolates from France were also resistant to nalidixic acid; the isolates we have obtained from fresh quails imported from France are possibly related to these isolates. The global food-products trade is expected to increase in the future. Thus, attempts to improve food safety must emphasize detection of antimicrobial drug–resistant bacteria in imported food products. Furthermore, international agreements that limit contamination with drug-resistant bacteria and resistance genes at the primary production site are necessary to ensure consumer safety (9). International agreements must be based on antimicrobial-resistance data and early reports of emerging problems. Recently, the World Health Organization (WHO) launched the Global Salm Surv program (10) to isolate and identify antimicrobial resistance to Salmonella globally. Many national and international rules, as well as marketing and consumer factors, regulate the international trade of food products and live animals. Large international corporations may also affect international trade. For example, McDonald's Corporation has issued a global policy for antimicrobial drug use in food animals that specifies requirements for their food product suppliers. Local groceries or supermarkets may also impose their own standards nationally. We are aware of only 1 product withdrawal related to antimicrobial resistance, the quail imported from France. No international standards exist for managing food safety problems related to antimicrobial resistance. However, in 2003 the Food and Agriculture Organization of the United Nations, WHO, and the World Organisation for Animal Health jointly hosted a workshop with a panel of experts to scientifically assess resistance risks related to nonhuman use of antimicrobial drugs (9). The panel's purpose was also to provide recommendations to the Codex Alimentarius Commission for future risk management of antimicrobial drug resistance (9). Imposing restrictions on products with combinations of resistance, such as simultaneous resistance to quinolones and cephalosporins in Salmonella, as reported in this study, would be a good first step towards managing antimicrobial drug–resistance risks.

Fluoroquinolone Use in Food Animals

To the Editor: Two recent articles (1,2) show that fluoroquinolone use in food animals is associated with infections by antimicrobial drug–resistant strains of Campylobacter in humans. These infections cause problems in treating illnesses as well as increased rates of illness and death (3). Despite a large body of scientific evidence and a judicial review (1–3) that show harmful results in many persons, some members of the poultry and pharmaceutical industries argue that fluoroquinolone use in food animals has no adverse effects in humans (4) and continue to supply these drugs for use in poultry (2,5). The use of these drugs has caused rapidly increasing resistance rates in most countries. In the United States, 19% of Campylobacter isolates from humans are now ciprofloxacin resistant (2), and resistance rates >80% are seen in Spain (5). By contrast, in Australia, where fluoroquinolones were never approved for use in food animals, domestically acquired infections with fluoroquinolone-resistant Campylobacter spp. are rarely found in humans (6). Drug-resistant Escherichia coli is also of concern. In Spain, humans frequently acquire fluoroquinolone-resistant E. coli associated with fluoroquinolone use in poultry (7). In the United States, better controls in meat and poultry slaughter and processing, as well as improved food-safety education campaigns, have resulted in 28% fewer Campylobacter infections annually since 1996 (8). However, ≈1.8 million persons (600 per 100,000) are likely to contract symptomatic Campylobacter infections per year (3,8), and fluoroquinolone resistance is now 19% (2). Thus, the risk of a person's contracting fluoroquinolone-resistant Campylobacter infection is 114 per 100,000 per year. If 80% of Campylobacter infections are foodborne (3), and 90% of these infections are acquired from poultry (9), then ≈82 of 100,000 persons per will contract ciprofloxacin-resistant Campylobacter infections from poultry each year. Most persons with Campylobacter infections would not benefit from antimicrobial drug therapy. However, if only 10% of infected persons would benefit from antimicrobial drug therapy, fluoroquinolone use in poultry could cause ≈82 persons per million to have a compromised response to therapy. In the United States (population 300 million), this number translates to >24,000 persons annually. Data on the number of animals that receive fluoroquinolones are difficult to find. Bayer (manufacturer of the only fluoroquinolone used in poultry in the United States) states that (enrofloxacin) is used in <1% of US broiler flocks (4). This statistic allows us to estimate how many persons will potentially have an adverse outcome compared to the number of animals receiving fluoroquinolones. If 24,000 persons in the United States have an adverse outcome annually after <84 million chickens (1% of 8.4 billion) are treated with enrofloxacin, then ≈285 persons are at risk of having an adverse outcome for every 1 million chickens treated. This risk seems needless. In Australia, consequences from not using these agents in food animals (i.e., neither therapeutic nor prophylactic use is approved) have not been seen. Thus, I do not agree with Iovine and Blaser (1), who would allow fluoroquinolones to be used to treat sick food production animals. Bayer claims that Baytril is used for therapeutic purposes only... (4). Thus, continuation of fluoroquinolone use for these therapeutic purposes will allow the consequent development of resistant bacteria in humans, which will include resistant strains of Campylobacter, E. coli, and Salmonella. Discontinuing fluoroquinolone use by mass dosing (the current practice for poultry [10]) would decrease the amount of the drug used. However, why use fluoroquinolones at all? Narrower spectrum antimicrobial drugs (e.g., sulfonamides, amoxicillin) could be used to adequately treat sick animals. Surely E. coli drug resistance in food animals in the United States cannot be at a level that makes fluoroquinolones indispensable. If resistance levels to narrower spectrum antimicrobial drugs are at high levels, does this finding not imply that major changes concerning antimicrobial drug use in food animals are needed? Better methods are needed to accurately estimate how many persons are negatively affected annually because of the misuse of antimicrobial drugs in food animals. Compromised therapeutic outcomes occur in many persons throughout the world because of fluoroquinolone-resistant Campylobacter infections (10). Fluoroquinolone use is not essential for food animal production or the welfare of animals. Many ways to keep animals healthy and productive exist other than treating or trying to prevent infections with the mass use of antimicrobial drugs such as fluoroquinolones.

Public Health Consequences of Macrolide Use in Food Animals: A Deterministic Risk Assessment

The potential impact on human health from antibiotic-resistant bacteria selected by use of antibiotics in food animals has resulted in many reports and recommended actions. The U.S. Food and Drug Administration Center for Veterinary Medicine has issued Guidance Document 152, which advises veterinary drug sponsors of one potential process for conducting a qualitative risk assessment of drug use in food animals. Using this guideline, we developed a deterministic model to assess the risk from two macrolide antibiotics, tylosin and tilmicosin. The scope of modeling included all label claim uses of both macrolides in poultry, swine, and beef cattle. The Guidance Document was followed to define the hazard, which is illness (i) caused by foodborne bacteria with a resistance determinant, (ii) attributed to a specified animal-derived meat commodity, and (iii) treated with a human use drug of the same class. Risk was defined as the probability of this hazard combined with the consequence of treatment failure due to resistant Campylobacter spp. or Enterococcus faecium. A binomial event model was applied to estimate the annual risk for the U.S. general population. Parameters were derived from industry drug use surveys, scientific literature, medical guidelines, and government documents. This unique farm-to-patient risk assessment demonstrated that use of tylosin and tilmicosin in food animals presents a very low risk of human treatment failure, with an approximate annual probability of less than 1 in 10 million Campylobacter-derived and approximately 1 in 3 billion E. faecium–derived risk.

Principles of Bovine Pharmacology

Certain considerations must be taken into account whenever one decides to administer a drug to a food animal. Some issues are relevant to drug use in any species, while others are specific for drug use in food animals. General principles of drug use in food animals are discussed, including withholding time, appropriateness of drug choice, and the potential for adverse effects. Some specific drug classes and compounds are discussed in order to provide examples of the factors that go into therapeutic decision-making.

Book reviews

Books reviewed:Committee on Drug Use in Food Animals, Panel on Animal Health, Food Safety and Public Health, National Research Council and the Institute of Medicine,The Use of Drugs in Food Animals: Benefits and RisksDaniele Archibugi and Jonathan Michie, Trade, Growth and Technical ChangeSimon Ville, The Rural Entrepreneurs: A History of the Stock and Station Agent Industry in Australia and New ZealandTom Tietenberg, Environmental Economics and PolicyRobert Ackrill, The Common Agricultural PolicyKeith O. Fuglie and David E. Schimmelpfennig, Public‐Private Collaboration in Agricultural Research: New Institutional Arrangements and Economic Applications

Assessing the Associations Among Facility Design and Management Practices and Drug Use in Ontario Free-Stall Dairy Herds

In recent years, issues centered on drug use in food producing animals have emerged as major food safety concerns in this agricultural sector. The dairy industry must adopt practical management strategies that minimize drug use in cattle. These strategies need to be identified and must focus on husbandry practices and facility design that minimize animal stress, and that contain specific biosecurity, sanitation and nutritional recommendations to minimize disease-and therefore drug use-in food animals.

The use of drugs in food animals : benefits and risks, compiled by the Committee on Drug Use in Food Animals, National Research Council and Institute of Medicine, USA : book review

The Journal of the South African Veterinary Association (JSAVA), is a contemporary multi-disciplinary scientific mouthpiece for Veterinary Science in South African and abroad. It provides veterinarians in South Africa and elsewhere in the world with current scientific information across the full spectrum of veterinary science, diseases or other conditions that are endemic in, or particularly relevant to sub-Saharan Africa.