Antimicrobials In Veterinary Medicine Research Articles

A recent update on the use of antimicrobials for animal health in Yogyakarta, Indonesia

Background and Aim: Animal antimicrobials must be studied to determine if they have the same types, norms of use, and resistance patterns as those used in humans. This study aimed to facilitate the analysis of data on the use of antimicrobials in veterinary medicine and to aid in developing a strategy to prevent the emergence of antimicrobial resistance (AMR) in humans and animals. Materials and Methods: Data were obtained through a survey of 101 veterinarians working in animal clinics and independent practice in five regencies of Yogyakarta province. Results: Both of the antibiotics, antiparasitic (78.6%) and, antiseptic and disinfectant (68.0%), and antifungal (31.1%) were the most frequently used types of antimicrobials, while antivirals were the least used (9.7%). The most often treated animals with antimicrobials are pets (37%), followed by large and small livestock (30%), poultry (15%), and exotic animals (14%). Of the respondents, 89% were aware of the factors contributing to AMR, but only 47% monitored developments and expanded their understanding of AMR. The most common antibiotic classes were penicillin (71), tetracyclines (50), sulfonamides (41), fluoroquinolones (31), and aminoglycosides (27). Conclusion: All antimicrobials used in the animal health sector are also used in human medicine, which requires special consideration. This cross-use of antibiotics was a crucial factor in determining the cause of the spread of AMR between humans and animals. Keywords: animal health, antimicrobial use, Yogyakarta.

Resistance to antimicrobial preparations of Enterococcus isolated from milk during infectious mastitis in cows

For successful pharmacotherapy of animals, it is important to identify species of Enterococcus faecalis pathogens isolated from milk in infectious mastitis of cows, analyze the antibiogram and interpret the results, and laboratory control over the mechanisms of antibiotic resistance. This is necessary for veterinarians to rationally select antibacterial drugs and predict their clinical effectiveness. The purpose of the study was to study the resistance to antimicrobial drugs of Enterococcus faecalis bacteria isolated from milk in infectious mastitis of cows. In the period from 2021 to 2022, 100 strains of microorganisms were isolated from the mastitis milk of cows. The obtained strains were identified as gram-negative bacteria in 32% of isolation cases, gram-positive bacteria - 68%, of which 14% were Enterococcus faecalis. When interpreting the antibiogram, most isolates of Enterococcus faecalis are sensitive to tetracycline in 21.4% of isolation cases, ampicillin, amoxicillin in 100%. It was noted resistant to tetracycline in 78.6% of cases of isolation, gentamicin, cephalexin, cefotaxime, erythromycin, clindamycin, lincomycin, tobramycin, ceftriaxone and streptomycin in 100%. Antibiotic resistance correlates with the clinical failure of antimicrobials in veterinary medicine. Multi-resistance of Enterococcus faecalis to various groups of antibacterial agents leads to limited use of antibiotics, which significantly reduces the possibilities of therapy and affects the economic condition of agriculture.

O01 The consumption of human antibiotics in veterinary medicine, in Estonia, 2006–22

Abstract Objectives In the absence of authorized veterinary medicinal products, veterinarians can use authorized human medicines, if necessary. The number of registered veterinary medicinal products, including veterinary antibiotics, has increased, over the years. Reducing the use of medically important antimicrobials in veterinary medicine is increasingly important to avoid the development and spread of antimicrobial resistance. The aim of this study was to analyse 17 year trends in the use of human antibiotics in veterinary medicine, in Estonia. Methods The data of human antibiotics used in veterinary medicine are based on wholesaler’s reports collected by the Estonian State Agency of Medicines, in 2006–2022. The sales data include total sales of human antimicrobial medicinal products to veterinarians and are collected at package level per year, including the name of the medicinal product, identification number of the product, active substance, pharmaceutical form, strength, package size and number of sold packages. Results Between 2006 and 2022, the overall sales of human antibiotics to veterinarians increased from 40.6 kg in 2006 to 54.4 kg in 2022 (peak 71.6 kg in 2019). In Estonia, based on 17 years of data, 220 different human antimicrobial medicinal products were sold to veterinarians, an average 91 different products per year (range 79–101). The number of different human antibiotic substances used in veterinary medicine was 45 ± 2 per year, 60 in total. The most used antibiotics over the 17 years were orally administered amoxicillin, clindamycin, ciprofloxacin, sulfamethoxazole and doxycycline and injectable amoxicillin and cefazolin. The turnover of human antibiotics sold to veterinarians increased from 34 000 EUR in 2006 to 99 000 EUR in 2022. Over the years, analysed by the product form, the most sold human antibiotics for veterinary use were products for oral administration, accounted for 90% of total quantity of antibiotics (24 different substances), followed by injections (9%, 19 different substances) and dermatological and sensory preparations (0.6%, 7 and 9 different substances, respectively). From medically important antibiotics, meropenem, imipenem, piperacillin, ceftriaxone, vancomycin and mupirocin were used in small quantities throughout the years. Conclusions Despite the number of registered veterinary antibiotics having increased over the years, the consumption of human antibiotics used in veterinary medicine has increased by the total quantity and by the turnover. The number of human antibiotic substances and sold packages has no significant changes.

Impacts of Domestication and Veterinary Treatment on Mobile Genetic Elements and Resistance Genes in Equine Fecal Bacteria.

Antimicrobial resistance in bacteria is a threat to both human and animal health. We aimed to understand the impact of domestication and antimicrobial treatment on the types and numbers of resistant bacteria, antibiotic resistance genes (ARGs), and class 1 integrons (C1I) in the equine gut microbiome. Antibiotic-resistant fecal bacteria were isolated from wild horses, healthy farm horses, and horses undergoing veterinary treatment, and isolates (9,083 colonies) were screened by PCR for C1I; these were found at frequencies of 9.8% (vet horses), 0.31% (farm horses), and 0.05% (wild horses). A collection of 71 unique C1I+ isolates (17 Actinobacteria and 54 Proteobacteria) was subjected to resistance profiling and genome sequencing. Farm horses yielded mostly C1I+ Actinobacteria (Rhodococcus, Micrococcus, Microbacterium, Arthrobacter, Glutamicibacter, Kocuria), while vet horses primarily yielded C1I+ Proteobacteria (Escherichia, Klebsiella, Enterobacter, Pantoea, Acinetobacter, Leclercia, Ochrobactrum); the vet isolates had more extensive resistance and stronger PC promoters in the C1Is. All integrons in Actinobacteria were flanked by copies of IS6100, except in Micrococcus, where a novel IS5 family element (ISMcte1) was implicated in mobilization. In the Proteobacteria, C1Is were predominantly associated with IS26 and also IS1, Tn21, Tn1721, Tn512, and a putative formaldehyde-resistance transposon (Tn7489). Several large C1I-containing plasmid contigs were retrieved; two of these (plasmid types Y and F) also had extensive sets of metal resistance genes, including a novel copper-resistance transposon (Tn7519). Both veterinary treatment and domestication increase the frequency of C1Is in equine gut microflora, and each of these anthropogenic factors selects for a distinct group of integron-containing bacteria. IMPORTANCE There is increasing acknowledgment that a "one health" approach is required to tackle the growing problem of antimicrobial resistance. This requires that the issue is examined from not only the perspective of human medicine but also includes consideration of the roles of antimicrobials in veterinary medicine and agriculture and recognizes the importance of other ecological compartments in the dissemination of ARGs and mobile genetic elements such as C1I. We have shown that domestication and veterinary treatment increase the frequency of occurrence of C1Is in the equine gut microflora and that, in healthy farm horses, the C1I are unexpectedly found in Actinobacteria, while in horses receiving antimicrobial veterinary treatments, a taxonomic shift occurs, and the more typical integron-containing Proteobacteria are found. We identified several new mobile genetic elements (plasmids, insertion sequences [IS], and transposons) on genomic contigs from the integron-containing equine bacteria.

The Problem of Antibiotic Resistance Control: A Possible Alternative to Antimicrobials in Veterinary Medicine

Aim of Study: The study included prospects for using autogenous immunobiological drugs as an alternative to antimicrobials. Materials and Methods: For the analysis databases of WHO–World Health Organization, WOHA–World Organization for Animal Health, FAO–Food and Agricultural Organization, CDC–Center for Control and of disease prevention in the USA, ECDC– European Center for Disease Control and Prevention, EFSA–European Food Safety Authority, as well as informational Internet resources of scientific journals, normative legal acts of Ukraine. The Results: According to the results of the conducted analysis, the global spread of microorganisms resistant to the action of antimicrobial drugs was established, which jeopardizes the possibility of effective treatment of infectious diseases. In Ukraine, as in other developed countries of the world, strict regulation of the circulation of antimicrobials has been adopted at the legislative level, which inevitably leads to the limitation of their use. International experience shows that restrictions on the use of antimicrobial agents should be compensated by measures aimed at increasing the level of biosafety. The use of autogenous immunobiological drugs for the specific prevention of infectious diseases of bacterial etiology can be a reasonable alternative to antibiotics in veterinary medicine. Conclusions: The introduction of new rules for the circulation of veterinary antimicrobial drugs will significantly affect the level of use of antimicrobial drugs. A reasonable alternative to antimicrobial agents is the use of autogenous immunobiological agents.

Fizikalno-kemijske karakteristike i detekcija rezidua antibiotika u sirovom kravljem mlijeku isporučenom u tri industrije za preradu mlijeka u Alžiru

The uncontrolled use of antimicrobials in veterinary medicine may result in the presence of their residues in food matrices of animal origin such as milk. The aim of this study was to examine the physicochemical quality and to detect antibiotic residues (β-lactams and tetracyclines) in milk, as their presence has resulted in the rejection of significant quantities of milk for marketing. The study was conducted on 274 milk samples delivered to three milk-processing units located in the suburbs of Algiers and surrounding cities (Blida and Boumerdes). Antibiotic residue detection was performed using a fast screening test (BetaStar® Combo), with a reading result within five minutes. The results indicated that the milk processing industry of Blida had the highest rejected milk volumes (43.4%), followed by Algiers (24%) and Boumerdes (19.1%). Non-compliance of milk acidity was the first cause for milk rejection (47.6 %), followed by the presence of antibiotic residues (26.8%), and incompliance with requirements for density (13.4%) and fat levels (12.2%). The study revealed 22 positive cases (8.03%) of antibiotic residues. Among these, 90.91% were positive for β-lactams, and only 9.09% for tetracyclines. All tetracyclines cases and half of the β-lactams cases were found in the Blida milk processing company, indicating that the good practice of milk production and collection must be strengthened in that company.

Evaluating the Role of Veterinarians in the One Health Approach to Antimicrobial Resistance in Jordan

Background Antimicrobials, including antibiotics, antivirals, antifungals, and antiparasitics, are drugs used to prevent and treat infections in humans, animals, and plants. Objective This study aimed to evaluate the role of knowledge, attitudes, and practices of Jordanian veterinarians in combating antimicrobial resistance (AMR), and to summarize the registered veterinary drugs between 2017 and 2020. Methods The descriptive study data were collected using a standardized questionnaire focusing on knowledge, attitudes, and practices of Jordanian veterinarians. Results The results were analyzed descriptively and showed that the mean knowledge of the participants who agreed with the statement on AMR definition was 84%. The majority (95.65%) agreed that AMR is a challenge for the veterinary sector in Jordan and should be prioritized among other zoonotic diseases. Around 69% of the participants believe that the misuse and overuse of antimicrobials by quacks—fraudulent and unauthorized practitioners—are the main reasons for AMR challenge. The most common practice among the respondents was recommending clients (farmers, owners, etc) to practice good animal husbandry (80%). The study also revealed that there was a significant difference (P=.02) between attending training about AMR and their professional sector (private, public, and academic). Conclusions This study showed the importance of implementing a continuous education program on antimicrobial resistance to improve veterinarians’ knowledge in all aspects of antimicrobial resistance and to increase their advisory skills. Laws should also be enacted to ensure that veterinarians prescribe the correct antimicrobials and improve the surveillance system to monitor the use of antimicrobials in veterinary medicine.

National Monitoring of Veterinary-Dispensed Antimicrobials for Use on Pig Farms in Austria: 2015-2020.

Antimicrobial use in livestock production systems is increasingly scrutinised by consumers, stakeholders, and the veterinary profession. In Austria, veterinarians dispensing antimicrobials for use in food-producing animals have been required to report these drugs since 2015. Here, we describe the national monitoring systems and the results obtained for Austrian pig production over a six-year period. Antimicrobial dispensing is described using the mass-based metric, milligrams per population correction unit (mg/PCU) and the dose-based metric, Defined Daily Dose (DDDvet) per year and divided into the European Medicines Agency’s prudent use categories. Pig production was divided into breeding units, fattening farms, farrow-to-finish farms, and piglet-rearing systems. Over all six years and all pig production systems, the mean amount of antimicrobials dispensed was 71.6 mg/PCU or 2.2 DDDvet per year. Piglet-rearing systems were found to have the highest levels of antimicrobial dispensing in DDDvet, as well as the largest proportion of Category B antimicrobials, including polymyxins. Although progress has been made in promoting a more prudent use of antimicrobials in veterinary medicine in Austria, further steps need to be taken to proactively improve animal health and prevent disease to reduce the need for antimicrobials, particularly those critically important for human medicine, in the future.

The role of veterinarians in the One Health approach to antimicrobial resistance perspectives in Jordan

This study aims to evaluate the role of Jordanian veterinarians in terms of their knowledge, attitudes and common practices in combating antimicrobial resistance (AMR) and summarize the registered veterinary drugs between 2017 2020. Descriptive study data were collected using a standardized questionnaire that focused on the knowledge, attitudes, and practices of Jordanian veterinarians. The findings were analyzed descriptively; 84% of the participants agreed with the statement on the definition of AMR. The majority (95.65%) of participants agreed that AMR is a challenge for the veterinary sector in Jordan and that it should be prioritized over other zoonotic diseases. Approximately 69% of the participants believed that the misuse and overuse of antimicrobials by unqualified, fraudulent, or unauthorized practitioners is the primary reason for the rise of cases associated with AMR and the challenges that accompany these. The most common practice among the respondents in this study was to recommend clients (e.g., farmers and owners) to practice good animal husbandry (80.00%). The study also revealed that there was a significant difference (p = 0.015) between attendance at AMR training sessions and the professional sector (private, public, and academic) of the veterinarians. This study underscores the importance of implementing a continuous education program on AMR so as to enhance the all-round knowledge of veterinarians and improve their advisory skills. In addition, laws should be enacted to ensure that veterinarians prescribe the correct antimicrobials and to improve surveillance systems for monitoring the use of antimicrobials in veterinary medicine.

Oxacillin (Methicillin) Resistant Staphylococci in Domestic Animals in the Czech Republic.

The aim of this study was to describe the prevalence of different Staphylococcus species isolated from pathological processes and lesions in domestic animals in the Czech Republic and to detect and describe oxacillin (methicillin)-resistant strains (MRS). During the years 2019–2020, a total of 5218 veterinary clinical samples from the Czech Republic were tested. Testing was performed by culture methods and typing by molecular phenotypic methods MALDI-TOF MS and PCR. Antimicrobial susceptibility testing of the strains was performed by the disk diffusion method. A total of 854 staphylococci strains were identified (16.37% prevalence), out of which 43 strains of 6 species of staphylococci were MRS (n = 43; 0.82% prevalence). Of the MRS strains, the most prevalent species were Staphylococcus pseudintermedius (n = 24; 0.46% prevalence) and Staphylococcus aureus (n = 7; 0.13% prevalence). Susceptibility testing showed resistance to beta-lactam antibiotics and, depending on the species, also to trimethoprim/sulfamethoxazole, gentamicin, tetracycline, erythromycin, clindamycin, and enrofloxacin. For further characterization of MRS, PCR assay for virulence factor genes was performed. Seven of the 14 target genes were observed only in S. aureus, except for the eno gene encoding laminin-binding protein, which was also detected in other staphylococci. It is necessary to emphasize the issue of correct using of antimicrobials in practice and antibiotic policy in university teaching and to create stricter legislation that would prevent the widespread use of antimicrobials in veterinary medicine, especially in livestock to reduce the emergence and spread of antimicrobial resistance.

Antimicrobial susceptibility of cinnamon and red and common thyme essential oils and their main constituent compounds against Streptococcus suis.

Streptococcus suis is an emerging zoonotic pathogen causing different diseases, in both humans and pigs. Generally, the control of this pathogen is based on antimicrobial therapy, but the development of bacterial resistance has led one to look for new options. In this sense, the essential oils (EOs) constitute a promising alternative. The activity of cinnamon, common thyme and red thyme EOs and their main active compounds (cinnamaldehyde and thymol) against S. suis isolates from pigs (n = 50) and humans (n = 6) was determined by the broth microdilution method. MIC50-90, MBC50-90 and the bactericidal index (BI) (minimal bactericidal concentration (MBC)/minimal inhibitory concentration (MIC)) were calculated. Also, the time-kill curve of each product against the S. suis P1/7 European reference strain was determined. No differences in the MIC or MBC values were observed between all the tested products, which suggest a homogeneous behaviour of S. suis, independently of their origin, organ of isolation or resistance profile. All the products showed a concentration-dependent and time-dependent killing activity and achieved the virtual eradication of S. suis at supra-inhibitory concentrations within the first 5 min of exposure, except cinnamaldehyde that showed only bacteriostatic effect. It suggests that these products could be utilized as antimicrobials in veterinary medicine for the control of this zoonotic pathogen.

Resistance to veterinary antimicrobials of Staphylococcus aureus from mastitic milk

Abstract Background Use of antimicrobials in veterinary medicine for prophylactic and therapeutic purposes is one of the main culprits for the selection of antimicrobial resistant bugs that currently threaten human and animal health. Therefore, surveillance on antimicrobial resistance (AMR) selection trends in animal husbandry is of utmost importance to prevent the spread of resistant bugs to humans. The species Staphylococcus aureus (Sa), that is of particular concern for the spread of methicillin-resistant (MRSA) strains, often causes mastitis in milk producing animals, thus requiring antibiotic treatment that can impact on the AMR status of this pathogen. With the aim of elucidating the current evolution of AMR in Sa involved in mastitis and the threats posed by the consumption of raw milk or inadequately pasteurized dairy products, data from antimicrobial susceptibility testing carried out on Sa strains from mastitis in years 2013 - 2019 in Molise region, Italy, were analyzed. Methods Sa isolates were tested by disk diffusion and inhibition halo sizes were converted in Minimum inhibitory concentrations (MIC) according to the EUCAST standards for the antibiotics there included. One isolate per AMR profile per farm was considered to define the percentage of the antibiotic resistant on the total number of isolates per year. Results The number of diagnosed Sa infections per year ranged between seven and nineteen, with a total of 78 isolates from 70 farms. The percentages of those resistant to aminoglycosides kanamycin, neomycin and paromomycin, to the macrolide tylosin and the multi drug resistant (MDR) isolates increased since 2015. The latter ranged between 26.3 and 85.7%. Conclusions AMR and MDR Sa in milk producing animals pose a serious risk to public health and needs stricter surveillance. Key messages Limiting use of antibiotics is needed to revert the trend. AMR Sa strains in dairy products, need to be kept under control for the strict connection with human health.

A Retrospective, Observational Study on Antimicrobial Drug Use in Beef Fattening Operations in Northwestern Italy and Evaluation of Risk Factors Associated with Increased Antimicrobial Usage.

Simple SummaryAntimicrobial usage in veterinary medicine is thought to be a source of antimicrobial resistance, with possible implications for human health. Certain antibiotics are considered critical for human health, and their use is being judiciously reduced in animal productions. The monitoring of antimicrobial consumption in animal production is key to lowering the risk of the development of antimicrobial resistance. With this study, we quantified antimicrobial usage in beef fattening operations in northwestern Italy before the implementation of a program intended to control antimicrobial usage in veterinary medicine. We found that antimicrobials defined as critical for human health (e.g., fluroquinolones) were often used also for metaphylactic treatment.The abuse or misuse of antimicrobials in animal production is thought to be a potential factor in the development of antimicrobial resistance in veterinary and human medicine. With this study, we wanted to quantify antimicrobial usage in beef fattening operations in northwestern Italy and to identify factors potentially influencing antimicrobial usage. The sample was composed of 26 beef fattening operations that import heifers and bulls from France. Data were extracted from the 2014 and 2015 treatment registers kept by the farmers. The mean (±SD) number of animal daily doses per animal (nADDa) per year for each farm was 3 (±2.1) during the study period (2014–2015). Group antimicrobial treatments (57.5% of all treatments) were often administered orally (70.5%) and consisted overwhelmingly of doxycycline (97%). Individual treatments (42.5% of all treatments) were administered parenterally (98.1%) and the most often used active substances were florfenicol (19.9%), marbofloxacin (19.5%), and tylosin (12.4%). There was a negative correlation between the nADDa for total and group treatments and average batch weight at arrival and between the amount of straw added per animal per day and the nADDa (p ≤ 0.05). Our data show that antimicrobials critical for human medicine were often used in beef fattening operations in northwestern Italy before the European guidelines for the prudent use of antimicrobials in veterinary medicine were issued. Additionally, the use of antimicrobials as a preventive group treatment was still widespread, mostly in lighter weight animals.

The Use of Colistin in Food-Producing Animals in Estonia—Vaccination as an Effective Alternative to Consumption of Critically Important Antimicrobials in Pigs

Reducing the use of critically important antimicrobials in veterinary medicine is increasingly important to avoid the development and spread of antimicrobial resistance. The aim of this study was to analyse ten-year trends of colistin consumption in Estonia and to ascertain the possible association between Escherichia (E.) coli vaccination and colistin consumption in pig production. Colistin sales data (2010–2019) were collected from the wholesalers, allowing differentiation of target species. In Estonia, the amount of sold colistin increased constantly and almost doubled from 2010 to 2013, and decreased from 2013 to 2019 by 92.5% in total. On average across a ten-year study period, 89.7% of colistin was used in pig production. The number of sold doses of E. coli vaccines for pigs was very low before 2014 (<2000) and increased drastically to 2019 (362,000). According to linear time-series model with autoregressive integrated moving average (ARIMA) the consumption of colistin in pigs decreased on average by 0.23 mg/PCU for every 10,000 E. coli vaccine doses (95% CI −0.39, −0.06; p = 0.006) over ten years. This study revealed that in pig production, vaccination against E. coli strains contributes to the expected downward trend in colistin consumption.

Last Call for Replacement of Antimicrobials in Animal Production: Modern Challenges, Opportunities, and Potential Solutions.

The constant market demand for easily available and cheap food of animal origin necessitates an increasing use of antibiotics in animal production. The alarming data provided by organizations monitoring drug resistance in indicator and pathogenic bacteria isolated from humans and animals indicate a possible risk of a return to the preantibiotic era. For this reason, it seems that both preventive and therapeutic measures, taken as an alternative to antimicrobials, seem not only advisable but also necessary. Nevertheless, the results of various studies and market analyses, as well as difficulties in the implementation of alternative substances into veterinary medicine, do not guarantee that the selected alternatives will completely replace antimicrobials in veterinary medicine and animal production on a global scale. This publication is a brief overview of the drug resistance phenomenon and its determinants, the steps taken to solve the problem, including the introduction of alternatives to antimicrobials, and the evaluation of some factors influencing the potential implementation of alternatives in animal production. The review also presents two groups of alternatives, which, given their mechanism of action and spectrum, are most comparable to the effectiveness of antibiotics, as emphasized by the authors.

Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses

SummaryThe use of antimicrobials in veterinary medicine is under great scrutiny with the emergence of antimicrobial resistance in the human population. Equine veterinarians rely on antimicrobials as an essential tool for the treatment of infections in horses, but there is much criticism of some use, particularly prophylaxis. While the appropriate use of antimicrobials can be justified in equine medicine, the misuse cannot. The definition of appropriate use is complex and involves the indication for therapy, antimicrobial selection, dosing regimen and timing and route of administration, duration of therapy and modification of therapy based on microbial susceptibility and clinical response. The aim of this article is to provide guidance on these factors to assist equine veterinarians in determining what constitutes appropriate antimicrobial use in horses.

Comparative pharmacokinetics of chlortetracycline, tetracycline, minocycline, and tigecycline in broiler chickens

Tetracyclines continue to be important antimicrobials in veterinary medicine. However, the pharmacokinetics (PK) of tigecycline (TIG) and minocycline (MIN) in broiler chickens has not been investigated to date, and the PK of chlortetracycline (CTC) and tetracycline (TET) remains insufficiently researched, especially in terms of absorption. These antimicrobials have never been compared in a single setting in a single species; therefore, the aim of the present study was to compare the PK of TIG, MIN, CTC, and TET in broiler chickens. Each drug (10 mg/kg) was administered intravenously (IV) and orally (PO). The plasma concentrations of each drug were determined by liquid chromatography-tandem mass spectrometry, and the results were analyzed using compartmental and non-compartmental PK models. Despite the fact that all of the studied antimicrobials were administered at an identical IV dose, the area under the concentration–time curve between zero and the last sampling point (AUC0→t) for MIN (35,014 ± 3,274 μg × hour/mL) and CTC (41,851 ± 10,965 μg × hour/mL) differed significantly from that determined for TIG (18,866 ± 4,326 μg × hour/mL) and TET (17,817 ± 4,469 μg × hour/mL). After IV administration, the values of AUC0→t were also directly related to total body clearance values which were significantly higher for TIG (0.56 ± 0.14 L/hour × kg) and TET (0.60 ± 0.14 L/hour × kg) than for CTC (0.25 ± 0.05 L/hour × kg) and MIN (0.29 ± 0.03 L/hour × kg). In turn, after PO administration, TIG was absorbed in only 1.55% ± 0.82, and CTC in 30.54% ± 6.99, whereas the bioavailability of MIN and TET was relatively high at 52.33% ± 3.92 and 56.45% ± 9.71, respectively. The differences in PK parameters between these drugs, despite their structural similarities, suggest that active transport mechanisms may play a role in their absorption and distribution.

TURNOVER OF ANTIMICROBIAL VETERINARY MEDICINAL PRODUCTS IN UKRAINE AS A FACTOR OF THEIR RATIONAL USE IN THE TREATMENT OF INFECTIOUS DISEASES IN ANIMALS

The procedure for manufacture, sale and rational use of antimicrobial veterinary medicinal products in veterinary medicine must comply with the national legislation, namely the Law of Ukraine “On Veterinary Medicine”. Only authorized in Ukraine veterinary medicinal products have been used in veterinary medicine as required with the recommendations stated in package leaflet, labeling and summary of the product characteristic. The article describes main principles of monitoring process sales turnover of antimicrobial veterinary medicinal products during period of study 2015-2018.&#x0D; On the suggestion of the World Organization for Animal Health (OIE) at the beginning of 2016 Ukraine started collecting annual sales data (for the previous year) on antimicrobial veterinary medicinal products in food-producing and domestic animals in accordance with the Chapter 6.9. of the Terrestrial Animal Health Code, 2016; 2018.&#x0D; The main goal of this study was the implementation of OIE recommendations in monitoring process by the assessment of sales patterns of antimicrobials, their influence on prudent use, in compliance with Ukrainian National Action Plan Tackling Antimicrobial Resistance, 2019. The study was conducted during four 12-month periods (from January 1 to December 31) during 2015-2018. The data in questionnaires reports were received from marketing authorization holders and distributors and collected as suggested by OIE. The specification of the amounts of the antimicrobials annual sales during 2015-2018 according route of administration and antimicrobial classes in [kg] and [%] of active ingredient were presented.&#x0D; The study revealed the main high-selling classes of antimicrobials (Tetracyclines, Penicillins and Sulfonamide+Trimethoprim); the commonly used route of administration (oral ~ 90 %) and part of veterinary critically important and important antimicrobials in total sales amounts of all antimicrobial veterinary medicinal products. Macrolides occupied the main part (10,2 %) in veterinary critically important antimicrobial medicinal products; part of Aminoglycosides was ~ 4 %; Fluoroquinolones – among 2,5 - 7,14 % and part of Cephalosporins was less than 1% during all years of the study.&#x0D; This study can be considered as the first step towards implementation a national monitoring system for rational and prudent use of antimicrobials in veterinary medicine.

Close to a Decade of Decrease in Antimicrobial Usage in Danish Pig Production-Evaluating the Effect of the Yellow Card Scheme.

The emergence and dissemination of antimicrobial resistant pathogens have led to rising concern about the widespread and excessive use of antimicrobials in veterinary medicine. Denmark has implemented several initiatives to reduce antimicrobial use in animals since the 90s, with the Yellow Card scheme implemented in 2010. The aim of the present study is to investigate the effects on antimicrobial use in Danish pig farms of changes in the legislation regarding the Yellow Card, based on analysis of temporal trends in monthly antimicrobial consumption calculated at herd-level from 2010 to 2017. A dynamic linear model with a linear growth component was used to model the data. The percentage of herds with a negative growth component and a significant decline below zero (based on 95% credible intervals) was assessed for the entire study period. The analysis was run separately for the different age groups within each farm: weaners (up to 30 kg), sows and finishers herds, and categorized according to antimicrobial use before the Yellow Card initiative (2008–2009), as groups of herds with “low,” “moderate,” or “high” consumption. The results evidence a decline of the antimicrobial consumption in Danish pig herds, more pronounced during two periods: with the introduction of the Yellow Card and in relation to the announcements and changes in the legislation in 2014. Weaner herds in the high consumption category had the highest percentage of herds with a negative growth component, reaching 82% of herds in January 2011, followed by weaner herds with moderate antimicrobial consumption reaching 71% of herds in October 2012. For finisher herds in the moderate consumption category, the proportion with a negative growth increased from 38% in January 2010 to 71% in July 2011. A decline in antimicrobial consumption was also evident after announcements and changes in the legislation in 2014, particularly for sows and finishers. Our findings suggest that changes in the Yellow Card scheme promoted a continuous reduction in antimicrobial use in Danish pig herds, particularly in herds with high antimicrobial consumption.

Effectiveness of alternative measures to reduce antimicrobial usage in pig production in four European countries

BackgroundThe reduction of antimicrobial usage (AMU) is in the focus in modern pig production. The objective of this study was to assess the effectiveness of alternatives to reduce AMU at herd level. In a prospective study, 68 farrow-to-finish pig herds located in Belgium, France, Germany and Sweden were recruited on a voluntary basis to implement tailor-made intervention plans to reduce their AMU. Alternative measures included improvement of biosecurity (n = 29 herds), vaccination (n = 30), changes of feeding schemes or drinking water quality (n = 45), improved pig health and welfare care (n = 21) as well as changes in stable climate and zootechnical measures (n = 14). Herds were followed for 1 year after implementation of measures. Annual antimicrobial expenditures or treatment records, as well as disease incidence scores were collected and compared to those of the year before intervention. AMU was measured as the treatment incidence and calculated by age category, antimicrobial class and administration route.ResultsCompliance with the intervention plans was high (median 93%). AMU was significantly reduced following the implementation of alternative measures: in the median herd of the four countries, pigs were treated before intervention 25% of their expected lifespan (200 days from birth to slaughter) and after intervention 16%. AMU of suckling and weaned pigs were significantly reduced by 37 and 54%, respectively. The usage of polymyxins and tetracyclines was significantly reduced by 69 and 49%, respectively. AMU via feed and water, as well as parenteral AMU were significantly reduced by 46 and 36%, respectively. Herds with a higher AMU level before intervention achieved a bigger reduction. The majority of disease incidence were similar before and after intervention, with a few exceptions of disorders related to the gastro-intestinal tract in suckling pigs (decreased) and in breeding pigs (increased).ConclusionFollowing tailor-made implementation of alternative measures, a substantial reduction of AMU in pig production was achievable without jeopardizing animal health. The AMU reduction in the youngest age categories (suckling and weaned pigs) and the reduction of group treatments via feed and water was in line with the recent European Guidelines on the prudent use of antimicrobials in veterinary medicine.