Use Of Drugs In Animals Research Articles

Characterizing the antimicrobial resistance profile of Escherichia coli found in sport animals (fighting cocks, fighting bulls, and sport horses) and soils from their environment.

Antimicrobial resistance (AMR) is a significant threat to global health and development. Inappropriate antimicrobial drug use in animals cause AMR, and most studies focus on livestock because of the widespread use of antimicrobial medicines. There is a lack of studies on sports animals and AMR issues. This study aimed to characterize the AMR profile of E. coli found in sports animals (fighting cocks, fighting bulls, and sport horses) and soils from their environment. Bacterial isolation and identification were conducted to identify E. coli isolates recovered from fresh feces that were obtained from fighting cocks (n = 32), fighting bulls (n = 57), sport horses (n = 33), and soils from those farms (n = 32) at Nakhon Si Thammarat. Antimicrobial resistance was determined using 15 tested antimicrobial agents - ampicillin (AM), amoxicillin-clavulanic acid, cephalexin (CN), cefalotin (CF), cefoperazone, ceftiofur, cefquinome, gentamicin, neomycin, flumequine (UB), enrofloxacin, marbofloaxacin, polymyxin B, tetracycline (TE), and sulfamethoxazole/trimethoprim (SXT). The virulence genes, AMR genes, and phylogenetic groups were also examined. Five virulence genes, iroN, ompT, hlyF, iss, and iutA, are genes determining the phylogenetic groups, chuA, cjaA, and tspE4C2, were identified. The AMR genes selected for detection were blaTEM and blaSHV for the beta-lactamase group; cml-A for phenicol; dhfrV for trimethoprim; sul1 and sul2 for sulfonamides; tetA, tetB, and tetC for TEs; and qnrA, qnrB, and qnrS for quinolones. The E. coli derived from sports animals were resistant at different levels to AM, CF, CN, UB, SXT, and TE. The AMR rate was overall higher in fighting cocks than in other animals, with significantly higher resistance to AM, CF, and TE. The highest AMR was found in fighting cocks, where 62.5% of their isolates were AM resistant. In addition, multidrug resistance was highest in fighting cocks (12.5%). One extended-spectrum beta-lactamase E. coli isolate was found in the soils, but none from animal feces. The phylogenetic analysis showed that most E. coli isolates were in Group B1. The E. coli isolates from fighting cocks had more virulence and AMR genes than other sources. The AMR genes found in 20% or more of the isolates were blaTEM (71.9%), qnrB (25%), qnrS (46.9%), and tetA (56.25%), whereas in the E. coli isolates collected from soils, the only resistance genes found in 20% or more of the isolates were blaTEM (30.8%), and tetA (23.1%). Escherichia coli from fighting cock feces had significantly higher resistance to AM, CF, and TE than isolates from other sporting animals. Hence, fighting cocks may be a reservoir of resistant E. coli that can transfer to the environment and other animals and humans in direct contact with the birds or the birds' habitat. Programs for antimicrobial monitoring should also target sports animals and their environment.

Elucidation of the effect of concomitant administration of Metformin and Diclofenac Sodium on insulin resistance, pro-inflammatory cytokines and oxidative stress markers in in vivo models

Prevalence of chronic disorders like arthritis is frequently observed in diabetic patients, especially among the geriatric population. To combat such a situation, non-steroidal anti-inflammatory drugs (NSAIDs) are mostly co-prescribed along with antidiabetics. Thus present study tried to evaluate the safety and efficacy of concomitant use of drugs in animals induced with comorbid conditions. Diabetes and chronic inflammation were induced in rats by Streptozotocin and Nicotinamide and Freund’s Complete Adjuvant respectively. These medical conditions were treated with antidiabetic Metformin and NSAID Diclofenac Sodium for 28 days. Blood glucose, paw edema were recorded weekly. At the end of the study duration, Insulin, C-peptide, cytokines in serum, oxidative stress biomarkers in liver and kidney tissues were estimated. Concomitant therapy of Metformin and Diclofenac Sodium was successful in reducing the glucose level and inflammation parameters. However, reduction by 30.06% and 46.51% in insulin and C-peptide levels respectively were evident in the rats treated with concomitant medications as compared to the normal. Concomitant therapy also failed to restore the normal levels of the pro-inflammatory cytokines. Perturbation was also evident in the antioxidant status of the tissues. Results from this study can thus be utilized to optimize the therapeutic regimen of patients to ensure safe medication.

Effects of N-Butanol and Aqueous Fractions of Khaya senegalensis, Guiera senegalensis and Tamarindus Indica Leaves Extracts on Eimeria tenella Oocyst Sporulation in Vitro

The in vitro anti coccidial activities of n-butanol and aqueous fractions of Khaya senegalensis, Gueira senegalensis and Tamarindus indica leaves extracts on Eimeria tenella parasite was studied by observing the effects of the plant extracts on the sporulation of the Eimeria tenella oocysts. Drug resistance and consumer demanding decrease in the use of drugs in animals have generated interest in alternative strategies to control the avian disease one of which is herbal intervention studies. Fresh faecal samples were collected from infected birds and their oocysts load determined. Dilutions of the extracts (100mg, 250mg, 400mg, 550mg, 700mg and 850mg per ml) in distilled water were prepared and placed in separate well labelled petri dishes. 100 oocysts were added to each petri dish and the set up was left at ambient temperature on the laboratory table and monitored twice daily (9.00am and 3.00pm) to observe the sporulation of the oocysts over a 72 hours period. Laboratory sporulation medium (2.5% Potassium dichromate) and Amprolium were used for comparison. The phytochemical result implied that the active ingredients were present mainly in the n-butanol and crude extract fractions with the nbutanol fraction of the Khaya senegalensis extract containing phenols and flavonoids which have antioxidant effects. The in vitro study showed that the n-butanol fraction of K senegalensis (100mg/ml) and the aqueous fraction of Tamarindus indica (100mg/ml) extracts had similar effects to those obtained using Amprolium which was considered as the standard by inhibiting the sporulation of Eimeria tenella oocysts. It is therefore recommended that more work needs to be done to determine the anti coccidial activities of these extracts in vivo.
 Key words: Eimeria tenella, sporulation, in vitro, extracts

Textual research on Xilei Powder

Xilei Powder is a commonly used prescription for the treatment of oral ulcers, and is originally used to treat scarlet fever. Scarlet fever is a warm-toxin disease from the perspective of the theory of warm disease. It is a warm infectious disease caused by epidemic. Xilei Powder was recorded in the Chinese Pharmacopoeia from 1953 edition to 2010 edition. As China joined Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), Xilei Powder was removed from the Chinese Pharmacopoeia of 2015 edition due to the limitation of the use of animal drugs, such as ivory and rhinoceros horn. Xilei Powder has been widely used to treat such diseases as otolaryngology, fever, gynecological diseases, digestive diseases, and tumors. Does Xilei Powder have a unique place in clinical application? Can stable and effective alternative drugs be derived from original prescription? Due to the lack of theoretical studies on Xilei Powder, by consulting ancient books, monographs and papers, we comprehensively summarized and studied historical evolution and prescription connotation of Xilei Powder, and analyzed its drug origin and clinical application, in the hope to promote the theoretical study and clinical application.

Features of adaptation and meat qualities of Aberdeen-Angus bulls on the background of immunostimulation

The feasibility of using Prevention-N-E, a newly developed and tested biological product, in comparison with the previously tested PS-6 preparation in the adaptive technology of keeping specialized beef cattle of imported breeding, had been scientifically substantiated and experimentally proved. Against the background of the use of drugs in animals of the 1st and 2nd experimental groups, the incidence of the digestive and respiratory organs decreased by 1.4 and 2.3 times, the recovery time reduced by 3.36 and 4.88 days, accordingly, compared with the control (P <0.05). By the end of the growing period, the animals of the 1st and 2nd experimental groups exceeded in live weight control subjects by 6.6 and 9.2 kg, rearing by 10.4 and 14.8 kg, and fattening by 14.2 and 22.2 kg respectively. In the cuts of the carcasses of bulls of the 1st and 2nd experimental groups, there was a bigger amount of the highest grade flesh: in spin-breast – by 1.0 and 1.0 kg, in the lumbar – by 0.2 and 0.4 kg, and in the hip – by 2.3 and 4.2 kg, rather than in the control.

Activization of adaptogenesis and realization of meat qualities of Aberdeen-Angus bulls by biological products

The feasibility of using Prevention-N-E, a newly developed and tested biological product, in comparison with the previously tested PS-6 preparation in the adaptive technology of keeping specialized beef cattle of imported breeding, had been scientifically substantiated and experimentally proved. Under the conditions of production tests, biopreparations PS-6 and Prevention-N-E stimulated the production of red blood cells and increased the hemoglobin concentration in the blood of bulls, that is, improved hematopoiesis; they caused physiological eosinophilia, moderate neutrophilopenia with a shift of the neutrophilic nucleus to the right and lymphocytosis; increased protein metabolism, mainly due to the synthesis of albumin and γ-globulin fractions; intensified nonspecific resistance of an organism. Against the background of the use of drugs in animals of the 1st and 2nd experimental groups, the incidence of the digestive and respiratory organs decreased by 1.4 and 2.3 times, the recovery time reduced by 3.36 and 4.88 days. accordingly, compared with the control (P <0.05). By the end of the growing period, the animals of the 1st and 2nd experimental groups exceeded in live weight control subjects by 6.6 and 9.2 kg, rearing by 10.4 and 14.8 kg, and fattening by 14.2 and 22.2 kg respectively (P <0.05-0.01). In the cuts of the carcasses of bulls of the 1st and 2nd experimental groups, there was a bigger amount of the highest grade flesh: in spin-breast - by 1.0 and 1.0 kg, in the lumbar - by 0.2 and 0.4 kg, and in the hip - by 2.3 and 4.2 kg (P <0.05-0.001), rather than in the control.

Medicated feeds and the Veterinary Feed Directive (VFD) in small ruminants

The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) amended the Food Drug &amp; Cosmetic Act to permit extralabel use of animal drugs under certain conditions. However, AMDUCA does not permit the extralabel use of medicated feed articles. Minor species such as sheep and goats (small ruminants) have very few animal drugs approved for their use and practitioners may determine that extralabel use is justified to prevent suffering and death. Compliance Policy Guide Sec. 615.115 Extralabel Use of Medicated Feeds for Minor Species (CPG 615.115) provides guidance on the current thinking of the Food and Drug Administration related to exercising enforcement discretion with regard to the extralabel use of medicated feeds in minor species. This presentation will walk through the CPG 615.115 from a practitioner’s perspective with goal of addressing common questions and situations where extralabel use of medicated feeds in sheep and goats may be indicated.

Analysis on Main Issues and Key Technologies of Real-time Monitoring of Veterinary Drug Production Process

Veterinary drug quality and safety is the key to the healthy development of animal husbandry. Veterinary drug quality is directly related to the safety of animal products and human health. In recent years, the Chinese government has promulgated regulations Good Manufacturing Practice of veterinary drugs and other regulations on the supervision of veterinary drug production process. However, the manufacture and sale of fake and inferior veterinary drugs and the illegal use of veterinary drugs are still prominent. It is urgent to further strengthen the quality and safety supervision of veterinary drugs. In the process of veterinary drug production, the identification and monitoring technology of HACCP key control points in veterinary drug production is studied, the dynamic real-time perception technology equipment of GMP key points in veterinary drug production is developed, the video analysis method of production operation specification is explored, and the traceability coding of minimum sales unit of veterinary drug is optimized. All these methods can realize the dynamic information monitoring on the production process of veterinary drugs. The research and implementation of the above-stated methods can strengthen the effective supervision of the source of veterinary drug production, ensure safe use of animal drugs, further improve the quality of livestock products, ensure food safety of people, and have significant economic and social benefits.

Source Attribution and Risk Assessment of Antimicrobial Resistance

Source attribution and microbial risk assessment methods have been widely applied for the control of several foodborne pathogens worldwide by identifying (i) the most important pathogen sources and (ii) the risk represented by specific foods and the critical points in these foods' production chains for microbial control. Such evidence has proved crucial for risk managers to identify and prioritize effective food safety and public health strategies. In the context of antimicrobial resistance (AMR) from livestock and pets, the utility of these methods is recognized, but a number of challenges have largely prevented their application and routine use. One key challenge has been to define the hazard in question: Is it the antimicrobial drug use in animals, the antimicrobial-resistant bacteria in animals and foods, or the antimicrobial resistance genes that can be transferred between commensal and pathogenic bacteria in the animal or human gut or in the environment? Other important limitations include the lack of occurrence and transmission data and the lack of evidence to inform dose-response relationships. We present the main principles, available methods, strengths, and weaknesses of source attribution and risk assessment methods, discuss their utility to identify sources and estimate risks of AMR from livestock and pets, and provide an overview of conducted studies. In addition, we discuss remaining challenges and current and future opportunities to improve methods and knowledge of the sources and transmission routes of AMR from animals through food, direct contact, or the environment, including improvements in surveillance and developments in genotypic typing methods.

Sex-specific attenuation of impulsive action by progesterone in a go/no-go task for cocaine in rats.

Previous work indicated that progesterone (PRO) reduced impulsive choice for cocaine in female but not male rats (Smethells et al. Psychopharmacology 233:2999-3008, 2016). Impulsive action, typically measured by responding for a reinforcer during a signaled period of nonavailability of natural reinforcers, predicts initiation and escalation of drug use in animals and humans. The present study examined impulsive action for cocaine using PRO in male and female rats trained on a go/no-go task. Rats were trained on a go/no-go task to respond for cocaine infusions (0.4mg/kg/inf). During the "go" component, responding was reinforced on a VI 30-s schedule, whereas during the "no-go" component, withholding a response was reinforced on a differential reinforcement of other behavior (DRO) 30-s schedule. A response during the no-go component resets the DRO timer and served as a measure of impulsive action. After baseline responding was established, rats were pretreated with vehicle (VEH) or PRO (0.5mg/kg), and DRO resets and responding during the go component for cocaine were compared in males vs. females. DRO resets were significantly lower following PRO treatment compared to VEH in female, but not male, rats. Response rates and overall infusions during the go component were not significantly altered by PRO in either females or males. Treatment with PRO resulted in a sex-specific reduction in impulsive action for cocaine, while not affecting cocaine self-administration.

Decline ofSalmonella entericaSerotype Choleraesuis Infections, Taiwan

To the Editor: Human salmonellosis is a major public health problem of global concern. Salmonella enterica serotype Choleraesuis is a nontyphoid serotype; it has a narrow host range and is associated with a high proportion of invasive infections (50%–90% of isolates are from sterile sites [(1)]). In 2000, emergence of fluoroquinolone resistance in S. enterica Choleraesuis was reported from Chang Gung Memorial Hospital at Linkou, Taiwan (2). Since then, we have continuously monitored the trend of these infections at this hospital in northern Taiwan and at Chang Gung Memorial Hospital at Kaohsiung in southern Taiwan. We report the decline of S. enterica Choleraesuis infections coinciding with the implementation of several national control programs in Taiwan. In humans, S. enterica Choleraesuis usually causes invasive infections (1). Transmission of the organism is probably from pigs to humans (3). According to an inspection program conducted by the Council of Agriculture in 2004, illegal slaughter of pigs dying of unidentified diseases and sale of the pork at a reduced price were common in Taiwan and probably were associated with transmission of the organism (4). In Taiwan during 1996–1997, a large epidemic of swine foot-and-mouth disease occurred (5), and consumption of pork decreased substantially. To prevent further spread of that epidemic, the government implemented massive slaughter of infected pigs and a swine vaccination policy (5). Coincidently, in 1996–1998, S. enterica Choleraesuis infections among humans decreased significantly (p<0.001) (2). However, during the following years, infections among humans and antimicrobial drug resistance gradually increased (2). In Taiwan, widespread use of antimicrobial drugs in animals, which might contribute to development of antimicrobial drug resistance in human pathogens, was subsequently reported (6). The Taiwan government took further actions to improve the quality of pig husbandry. In 2002, a live attenuated S. enterica Choleraesuis vaccine (Suisaloral; Impfstoffwerk Dessau-Tornau GmbH, Rosslay, Germany) for pigs was licensed for importation (veterinary drug license no. 06387) (7). In 2004, the following approaches were implemented to consolidate the management of animal husbandry and ensure the quality and safety of meat: improving pollution control and sanitary conditions in pig farms by periodic inspection and education programs; implementing regulations to promote and improve an existing quality food certification system, Certified Agricultural Standards, by tracking and auditing illicit labeling; reinforcing monitoring and tracking systems for the sale and consumption of antimicrobial drugs for animal use (by continuing education and inspections with or without fixed schedules); preventing illegal slaughtering and sale of pigs dying of unidentified diseases (by inspections and monetary penalties for violations); and establishing a Taiwan Agriculture and Food Traceability system (http://taft.coa.gov.tw) to fully record all processes from farm to table (4,8). A particularly notable control measure launched at that time was a death insurance program for pigs. Although farmers were fully compensated for their losses, pigs dying of unidentified diseases were collected and chemically marked to prevent the possibility of subsequent illegal use (4). In 2005, 2 representative counties in central-southern Taiwan tried the program. During the next year, the program was extended to 8 neighboring counties, and in 2007, it was implemented in all counties (9). Furthermore, since the establishment of the Taiwan Agriculture and Food Traceability system, various Taiwan Good Agricultural Practice manuals have been gradually developed, and in 2008, a manual for pig farming established official standard operating procedures (10). The control measures seem to be successful, as evidenced by the results of a long-term monitoring program at the 2 large tertiary care hospitals in northern and southern Taiwan (Figure). S. enterica Choleraesuis infections have declined significantly since 2005 in southern Taiwan (Figure, panel A) and since 2006 in northern Taiwan (Figure, panel B) (χ2 test for trend, p 80 in 2004–2005 to 24 in 2006 (Figure, panel B), when the death insurance program was expanded to more areas. At both hospitals, the annual number of S. enterica Choleraesuis infections had decreased consistently in the subsequent years; since 2008, this number has remained <10 (Figure). Figure Trends of annual numbers and percentages of Salmonella enterica serotype Choleraesuis isolates from 2 tertiary care hospitals in Taiwan. A) Data from Chang Gung Memorial Hospital at Kaohsiung, southern Taiwan. B) Data from Chang Gung Memorial Hospital ... After interruption of the identified infection chain, the substantial decline of infection among humans became evident. Despite the absence of national surveillance data for nontyphoid human salmonellosis in Taiwan, the decrease in S. enterica Choleraesuis infections reported herein has also been noted at other hospitals in Taiwan (L.-H. Su, pers. comm.). This finding demonstrates that application of effective control measures on farms and in agricultural practices can lead to successful control of S. enterica Choleraesuis infection among humans.

Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their highly pleiotropic nature, each miRNA has the potential to regulate hundreds or even thousands of protein-coding RNA transcripts. This property of miRNAs has generated considerable interest in their potential involvement in complex psychiatric disorders such as addiction, as each miRNA could potentially influence the many different molecular and cellular adaptations that arise in response to drug use that are hypothesized to drive the emergence of addiction. Here, we review recent evidence supporting a key role for miRNAs in the ventral striatum in regulating the rewarding and reinforcing properties of cocaine in animals with limited exposure to the drug. Moreover, we discuss evidence suggesting that miRNAs in the dorsal striatum control the escalation of drug intake in rats with extended cocaine access. These findings highlight the central role for miRNAs in drug-induced neuroplasticity in brain reward systems that drive the emergence of compulsive-like drug use in animals, and suggest that a better understanding of how miRNAs control drug intake will provide new insights into the neurobiology of drug addiction.

Pharmacokinetic of levamisole in speckled surubimPseudoplatystoma corruscans

Journal of Veterinary Pharmacology and TherapeuticsVolume 36, Issue 3 p. 298-301 Short Communication Pharmacokinetic of levamisole in speckled surubim Pseudoplatystoma corruscans R. B. Zanon, R. B. Zanon Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorB. S. Cerozi, B. S. Cerozi Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorT. S. C. Silva, T. S. C. Silva Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorJ. E. P. Cyrino, Corresponding Author J. E. P. Cyrino Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilJosé Eurico Possebon Cyrino, Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, P.O. Box # 9, 13418-900, Piracicaba, SP, Brazil. E-mail: jepcyrino@usp.brSearch for more papers by this author R. B. Zanon, R. B. Zanon Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorB. S. Cerozi, B. S. Cerozi Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorT. S. C. Silva, T. S. C. Silva Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilSearch for more papers by this authorJ. E. P. Cyrino, Corresponding Author J. E. P. Cyrino Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, BrazilJosé Eurico Possebon Cyrino, Departamento de Zootecnia, Setor de Piscicultura, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, P.O. Box # 9, 13418-900, Piracicaba, SP, Brazil. E-mail: jepcyrino@usp.brSearch for more papers by this author First published: 23 August 2012 https://doi.org/10.1111/jvp.12002Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume36, Issue3June 2013Pages 298-301 RelatedInformation

Antimicrobial use in food and companion animals

The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced 'prudent use guidelines' to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for 'antimicrobial stewardship', there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.

Antimicrobial Drug Consumption in Companion Animals

To the Editor: During the last decade, use of antimicrobial drugs for growth promotion and therapeutic treatment in food animals has received much attention. The reservoir of resistant bacteria in food animals implies a potential risk for transfer of resistant bacteria, or resistance genes, from food animals to humans. Subsequent emergence of infections in humans, caused by resistant bacteria originating from the animal reservoir, is of great concern. These unintended consequences of antimicrobial drug use in animals led to termination of antimicrobial growth promoters in food animals in countries in the European Union, including Denmark, where the consumption of antimicrobial drugs by production animals was reduced by 50% from 1994 to 2003 (1). In Denmark, the VetStat program monitors all veterinary use of medicines for animals. VetStat is based on reporting from the pharmacies and from veterinary practitioners and contains detailed information, such as animal species, reason for prescription, and dosage on each prescription. In Denmark, antimicrobial drugs can be obtained only by prescription and only at pharmacies. So far, use of antimicrobial drugs in companion animals has received little attention; monitoring programs have focused on antimicrobial drug consumption in food animals. According to data generated by the VetStat program in 2003, consumption of fluoroquinolones and cephalosporins in companion animals was substantial when compared to consumption in food animals (1). Fluoroquinolones and cephalosporins are antimicrobial drugs ranked by the U.S. Food and Drug Administration as critically important in human medicine, and for which emergence of resistant bacteria is especially undesirable (2). Considering the shared environment of humans and companion animals, transfer of resistant bacteria or mobile resistance determinants from companion animals to humans would be possible, and emergence of resistance to fluoroquinolones and cephalosporins in companion animals should be a matter of concern. Several scientific publications have reported the occurrence of the same resistance genes in companion animals and in humans (3–6) and the possible transfer of bacteria between companion animals and humans (3–9). Companion animal owners and their families are likely in close contact with their animals daily, which provides the opportunity for transfer of bacteria between companion animals and humans. A large proportion of the human population presumably has daily contact with companion animals, not only in Denmark but also in other countries. In Denmark, 20% of families own dogs and 16% own cats (10). In 2002, legal restrictions aimed to reduce the usage of fluoroquinolones in food animals were imposed in Denmark. The total annual consumption of fluoroquinolones in animals (companion and food animals) in Denmark was reduced from 183 kg in 2001 to 53 kg in 2003 (1). Of these 53 kg of fluoroquinolones, almost half (24 kg) was used in companion animals (data based on reporting on use in veterinary practice and sales from pharmacies on prescription). These data document that fluoroquinolones remain widely used for infections in companion animals, even though the emergence of fluoroquinolone resistance in bacteria is especially undesirable and regarded as a human health hazard. A similar situation exists with cephalosporins. The total consumption of cephalosporins in animals (companion and food animals) in Denmark in 2003 was 461 kg, of which more than half (254 kg) was consumed by companion animals (1). Thus, a comparatively small number of companion animals (550,000 dogs and 650,000 cats) (10) consume approximately the same amount of fluoroquinolones and cephalosporins as consumed annually in the much larger population of food animals in Denmark (23 million slaughter pigs, 130 million broiler chickens, and 1.2 million cattle and dairy cows) (10). We do not believe that antimicrobial drugs are more generously prescribed for companion animals in Denmark than in other industrialized countries. Rather, the data presented here reflect the apparent contrast between policies of antimicrobial drug use for food animals and policies for companion animals. The use of these antimicrobial drugs is avoided or restricted in food animals to minimize spread of resistance, while in companion animals prescription continues unimpeded. This situation may create undesirable antimicrobial drug resistance in bacteria, which may subsequently spread to humans from the previously neglected reservoir in companion animals.

Surgical implantation of transmitters into fish.

Although the Animal Welfare Act does not cover poikilotherms, individual institutions and policies and legal requirements other than the Animal Welfare Act (e.g., the US Public Health Service and the Interagency Research Animal Committee's Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training) require the review of projects involving fish by institutional animal care and use committees (IACUCs). IACUCs may, however, lack the knowledge and experience to evaluate fish projects judiciously, especially when the projects are in field settings. Surgeries involving implantation of transmitters and other instruments into the coelom, which now comprise a very common research tool in the study of free-ranging fishes, are examples of surgeries that use a broad spectrum of surgical and anesthetic techniques, some of which would not be considered acceptable for similar work on mammals. IACUCs should apply the standards they would expect to be used for surgeries on homeotherms to surgeries on fish. Surgeons should be carefully trained and experienced. Surgical instruments and transmitters should be sterile. Regulations and laws on the use of drugs in animals should be followed, particularly those concerned with anesthetics and antibiotics used on free-ranging fish. Exceptions to surgical procedures should be made only when circumstances are extreme enough to warrant the use of less than optimal procedures.

Emerging mechanisms of fluoroquinolone resistance.

Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections.

New animal drug approvals and the United States aquaculture industry: a partnership for growth

Aquaculture, for better or worse, depends in part on drugs for the prevention, control and eradication of a variety of diseases. The US Food and Drug Administration's Centre for Veterinary Medicine, through the Federal Food, Drug and Cosmetic Act, strictly controls the approval and use of drugs in animals, including aquatic animals. Laws and regulations exist that regulate the investigational use and approval of new animal drugs for all animals. However, in reality, these mandates must be uniquely interpreted for aquatic species. Very few drugs are approved for use in aquatic species. There is a growing effort by non-traditional sponsors (aquaculturists as opposed to pharmaceutical firms) to gain approvals for several new animal drugs. Simultaneously, the federal government, including the Centre for Veterinary Medicine, is working aggressively with the private and public aquaculture sectors to facilitate submission and subsequent approval of new animal drug applications. The drug approval procedures and requirements for aquatic animals are discussed. Special attention is given to their similarities and differences, relative to traditional terrestrial animals.

Good Manufacturing Practices

Good manufacturing practices (GMP) are required to be followed in the use of animal drugs to produce medicated feeds. The authority is found in the federal Food, Drug, and Cosmetic Act, which states that medicated feed can be deemed adulterated if GMP were not followed in its production. This authority has been translated into GMP regulations applicable to all medicated feed production. More detailed GMP are imposed on those using high potency sources of drugs that require a withdrawal period (Category II). Less detailed GMP are imposed on all other drug uses (Category I and lower potency sources of Category II). Facility registration, medicated feed applications, and biennial inspections are also imposed on those required to follow the more detailed GMP regulations. The basic thrust of the regulations is assurance that drug use is correct in all respects and that the integrity of all medicated and nonmedicated feeds is maintained. The objective is food free of illegal drug residues, i.e., food safety. The GMP regulations are based on joint industry-government endeavor and reflect the practical realities of feed manufacturing. They are, for all practical purposes, good business practices assuring that medicated feeds make a positive contribution to food production and consumer confidence.

Results of Drug Screening from a Producer's View

The dairy industry is faced with increasing governmental and public concern about the safety of the nation's milk supply. New regulations under the Grade A Pasteurized Milk Ordinance require that prescription drugs be properly labeled and that all tanker loads of milk be tested for β-lactam antimicrobial residues.Concern over the use of animal drugs in an extralabel manner has prompted the National Milk Producers Federation and the American Veterinary Medical Association to develop a quality assurance program for on-farm residue prevention known as the Dairy Quality Assurance 10-Point Milk and Dairy Beef Residue Prevention Protocol. The program promotes the concept of Hazard Analysis Critical Control Points, applied to a preharvest farm environment. Screening limitations at point of milk receipt necessitates widespread adoption of the Dairy Quality Assurance protocol to address controlled use of all animal medications under a valid relationship among veterinarian, client, and animals, thus minimizing the potential for violative residues in the milk and meat supply.