Antibiotics In Veterinary Medicine Research Articles

Development and evaluation of novel taste-masking tilmicosin microcapsules containing octenylsuccinic anhydride modified starch and maltodextrin as wall materials

Tilmicosin (TMS) is an important antibiotic in veterinary medicine, but its extreme bitter taste limits its use. In this study, TMS was encapsulated in octenyl succinic anhydride modified starch/maltodextrin (HI-CAP/MD) composite capsules with a spray drying method. The TMS microcapsules (TMS-MC) exhibited good drug loading performance with drug loading (DL) and encapsulation efficiency (EE) of 9.90 ± 0.23 % and 98.03 ± 1.56 %, respectively. There was no significant change in particle diameter and zeta potential for the emulsion and redissolved TMS-MC. These results combined with FT-IR, TGA and DSC showed the crystalline shape and chemical structure of TMS did not change during the microencapsulation. In vitro release characterization in an acidic medium (pH 1.2) and an alkaline medium (phosphate buffered solution, pH 6.8) showed that TMS-MC can be rapidly released in vitro. The bitterness evaluation implied the bitterness of TMS was masked after microencapsulation. In vitro bacterial inhibition test showed the bacterial inhibitory activity of TMS was not reduced by the microencapsulation, but was much better than that of the commercially available tylosin (TLS). Therefore, HI-CAP/MD can effectively encapsulate TMS, mask the bitter taste and maintain a good bacterial inhibitory effect, making a new drug formulation with good development prospects.

Screening of Neutralizing Antibodies against FaeG Protein of Enterotoxigenic Escherichia coli.

The misuse of antibiotics in veterinary medicine presents significant challenges, highlighting the need for alternative therapeutic approaches such as antibody drugs. Therefore, it is necessary to explore the application of antibody drugs in veterinary settings to reduce economic losses and health risks. This study focused on targeting the F4ac subtype of the FaeG protein, a key adhesion factor in enterotoxigenic Escherichia coli (ETEC) infections in piglets. By utilizing formaldehyde-inactivated ETEC and a soluble recombinant FaeG (rFaeG) protein, an antibody library against the FaeG protein was established. The integration of fluorescence-activated cell sorting (FACS) and a eukaryotic expression vector containing murine IgG Fc fragments facilitated the screening of anti-rFaeG IgG monoclonal antibodies (mAbs). The results demonstrate that the variable regions of the screened antibodies could inhibit K88-type ETEC adhesion to IPEC-J2 cells. Furthermore, in vivo neutralization assays in mice showed a significant increase in survival rates and a reduction in intestinal inflammation. This research underscores the potential of antibody-based interventions in veterinary medicine, emphasizing the importance of further exploration in this field to address antibiotic resistance and improve animal health outcomes.

Epidemiological study and identification of Escherichia coli strains associated with clinical events in Avian farming

Avian pathogenic Escherichia coli (APEC) represents a major challenge for the poultry industry, causing significant economic losses. This problem is exacerbated by the misuse use of antibiotics in Veterinary Medicine, leading to the emergence of resistant strains and thus creating a significant risk to Public Health. This study, carried out on 38 poultry farms in Algeria, involved the collection of 200 samples for the isolation of E. coli strains. The resistance of these strains to frequently used antibiotics was assessed using the agar diffusion method. Multiple Correspondence Analysis (MCA) was used to determine potential risk factors. The obtained results revealed that E. coli was present in 30% of samples. Alarming levels of resistance were observed against Tetracycline (81.6%), Ampicillin (78.3%), Ciprofloxacin (68.3%) and Nalidixic acid (60%). Stressful environmental conditions in poultry houses, such as temperature variations, high humidity, poor ventilation and stocking density were identified as key factors in the development of avian colibacillosis. In conclusion, the current study highlights the urgent need to strictly monitor and regulate the use of antibiotics in Veterinary Medicine and improve animal welfare in order to minimize the risk it pose to Public Health originated in the farms. In addition, it is essential that farmers maintain optimal environmental conditions in chicken rearing.

Core-shell molecularly imprinted polymer sensor for enrofloxacin determination in various matrices: a novel, sustainable One Health analytical strategy.

Antibiotics are essential in treating infectious diseases in both humans and animals, and they are also utilized to enhance animal growth. However, their widespread use has led to significant environmental concerns. After administration of antibiotics, a substantial portion of them is excreted by animals, contaminating various environmental compartments. This problem is examined from the One Health perspective which seeks to balance human, animal, and environmental health for the benefit of global well-being. Enrofloxacin (ENR) is a commonly used antibiotic in veterinary medicine. Despite its efficacy in animal health, ENR is not approved for human use due to its associated toxicities. To address ENR detection, a sensor built upon a core-shell molecularly imprinted polymer (MIP) was created for the determination and testing of ENR in different matrices. Offering a miniaturized and reproducible tool for determining antibiotic residues in biological and environmental samples helps in revolutionizing the way we monitor and control antibiotic usage and contamination in various settings. The fabricated sensor demonstrated an optimum response time and functioned effectively across the pH range of 2.0 to 5.0. The potential profile displayed a linear correlation within a varying concentration spectrum of 1.0 × 10-5 M to 1.0 × 10-2 M characterized by a slope of 57.21 mV per decade. Furthermore, a comprehensive assessment of the environmental sustainability of the developed method was carried out using the Analytical Greenness calculator, AGREE algorithm. Lastly, an examination of the method's level of environmental friendliness was pursued using the newly developed RGB12 model to evaluate its "whiteness" level.

Beyond the desert sands: Decoding the relationship between camels, gut microbiota, and antibiotic resistance through metagenomics

BackgroundCamels, known as the enduring “ships of the desert,” host a complex gut microbiota that plays a crucial role in their survival in extreme environments. However, amidst the fascinating discoveries about the camel gut microbiota, concerns about antibiotic resistance have emerged as a significant global challenge affecting both human and animal populations. Indeed, the continued use of antibiotics in veterinary medicine has led to the widespread emergence of antibiotic-resistant bacteria, which has worsened through gene transfer. MethodologyThis study offers a deeper examination of this pressing issue by harnessing the potent tools of metagenomics to explore the intricate interplay between the camel (Camelus ferus) gut microbiota and antibiotic resistance. ResultsSamples from wild camels yielded varying amounts of raw and clean data, generating scaftigs and open reading frames. The camel fecal microbiome was dominated by bacteria (mainly Bacillota and Bacteriodota), followed by viruses, archaea, and eukaryota. The most abundant genera were the Bacteroides, Ruminococcus, and Clostridium. Functional annotation revealed enriched pathways in metabolism, genetic information processing, and cellular processes, with key pathways involving carbohydrate transport and metabolism, replication, and amino acid transport. CAZy database analysis showed high abundances of glycoside hydrolases and glycosyl transferases. Antibiotic resistance gene (ARG) analysis identified Bacillota and Bacteroidota as the main reservoirs, with vancomycin resistance genes being the most prevalent. This study identified three major resistance mechanisms: antibiotic target alteration, antibiotic target protection, and antibiotic efflux. ConclusionThese findings contribute to a broader understanding of antibiotic resistance within animal microbiomes and provide a foundation for further investigations of strategies to manage and mitigate antibiotic resistance.

A colorimetric-aptamer-based assay for the determination of enrofloxacin through triggering the aggregation of gold nanoparticles.

Although enrofloxacin (ENR) is a widely used broad-spectrum antibiotic in veterinary medicine, its residues in animals can pose a risk to human health. Thus, we developed a new method for detecting ENR based on aptamers and AuNPs. In the absence of ENR, the aptamers attached to the surface of the AuNPs via electrostatic interactions to protect the AuNPs from NaCl, and the solution remained red. Conversely, the aptamer bonded with ENR, leading the aptamer to detach from the AuNP surface, and the color of the solution changed from red to blue. Based on this principle, ENR can be qualitatively detected by the naked eye and quantitatively detected by measuring the absorbance ratio at 650 nm and 530 nm. The experimental results showed a good linear relationship within the ENR concentration range of 0-400 nM, with a limit of detection (LOD) of 1.72 nM, which is satisfactory for detection in food safety. Additionally, this method has also been successfully applied to the detection of ENR in tap water, river water, milk, serum and urine, with good recovery rates and RSD values of less than 7%, indicating its great potential for ENR detection in environmental water samples. More importantly, the combination of this method with a smartphone platform provided great convenience for on-site and visual detection of ENR, offering promising applicability prospects.

Persistence of commensal multidrug-resistant Escherichia coli in the broiler production pyramid is best explained by strain recirculation from the rearing environment.

Despite the success of mitigation policies in several countries to reduce the use of antibiotics in veterinary medicine, pathogenic and commensal bacteria resistant to antibiotics are still circulating in livestock animals. However, factors contributing the most to antimicrobial resistance (AMR) persistence in these settings are yet not clearly identified. The broiler production, with its highly segmented, pyramidal structure offers an ideal context to understand and control the spread of resistant bacteria. By taking advantage of an experimental facility reproducing the whole broiler production pyramid, we demonstrate that resistant E. coli persist in our system primarily though recirculation of a few commensal clones surviving in the rearing environment. No vertical transmission from hens to offspring nor strain acquisition at the hatchery were detected, while import of new strains from outside the facility seems limited. Moreover, each clone carries its own resistance-conferring plasmid(s), and a single putative plasmid horizontal transfer could have been inferred. These results, observed for now in a small experimental facility with high level of biosecurity, must be confirmed in a commercial farm context but still provide invaluable information for future mitigation policies.

European Wild Carnivores and Antibiotic Resistant Bacteria: A Review.

Antibiotic resistance is a global concern that affects not only human health but also the health of wildlife and the environment. Wildlife can serve as reservoirs for antibiotic-resistant bacteria, and antibiotics in veterinary medicine and agriculture can contribute to the development of resistance in these populations. Several European carnivore species, such as wolves, foxes, otters, and bears, can be exposed to antibiotics by consuming contaminated food, water, or other resources in their habitats. These animals can also be indirectly exposed to antibiotics through interactions with domestic animals and human activities in their environment. Antibiotic resistance in wildlife can harm ecosystem health and also impact human health indirectly through various pathways, including zoonotic disease transmission. Moreover, the spread of resistant bacteria in wildlife can complicate conservation efforts, as it can threaten already endangered species. This review aims to describe the presence of antibiotic-resistant bacteria in wild carnivores in Europe.

Exploration of Tilmicosin Cardiotoxicity in Rats and the Protecting Role of the Rhodiola rosea Extract: Potential Roles of Cytokines, Antioxidant, Apoptotic, and Anti-Fibrotic Pathways.

Tilmicosin (TIL) is a common macrolide antibiotic in veterinary medicine. High doses of TIL can have adverse cardiovascular effects. This study examined the effects of Rhodiola rosea (RHO) that have anti-inflammatory, antioxidant, and anti-fibrotic effects on tilmicosin (TIL)-induced cardiac injury targeting anti-inflammatory, antioxidant, apoptotic, and anti-apoptotic signaling pathways with anti-fibrotic outcomes. Thirty-six male Wistar albino rats were randomly divided into groups of six rats each. Rats received saline as a negative control, CARV 1 mL orally (10 mg/kg BW), and RHO 1 mL orally at 400 mg/kg BW daily for 12 consecutive days. The TIL group once received a single subcutaneous injection (SC) dose of TIL (75 mg/kg BW) on the sixth day of the experiment to induce cardiac damage. The standard group (CARV + TIL) received CARV daily for 12 consecutive days with a single TIL SC injection 1 h after CARV administration only on the sixth day of study and continued for another six successive days on CARV. The protective group (RHO + TIL) received RHO daily for the same period as in CARV + TIL-treated rats and with the dosage mentioned before. Serum was extracted at the time of the rat's scarification at 13 days of study and examined for biochemical assessments in serum lactate dehydrogenase (LDH), cardiac troponin I (cTI), and creatine phosphokinase (CK-MB). Protein carbonyl (PC) contents, malondialdehyde (MDA), and total antioxidant capacity (TAC) in cardiac homogenate were used to measure these oxidative stress markers. Quantitative RT-PCR was used to express interferon-gamma (INF-γ), cyclooxygenase-2 (COX-2), OGG1, BAX, caspase-3, B-cell lymphoma-2 (Bcl-2), and superoxide dismutase (SOD) genes in cardiac tissues, which are correlated with inflammation, antioxidants, and apoptosis. Alpha-smooth muscle actin (α-SMA), calmodulin (CaMKII), and other genes associated with Ca2+ hemostasis and fibrosis were examined using IHC analysis in cardiac cells (myocardium). TIL administration significantly increased the examined cardiac markers, LDH, cTI, and CK-MB. TIL administration also increased ROS, PC, and MDA while decreasing antioxidant activities (TAC and SOD mRNA) in cardiac tissues. Serum inflammatory cytokines and genes of inflammatory markers, DNA damage (INF-γ, COX-2), and apoptotic genes (caspase-3 and BAX) were upregulated with downregulation of the anti-apoptotic gene Bcl-2 as well as the DNA repair OGG1 in cardiac tissues. Furthermore, CaMKII and α-SMA genes were upregulated at cellular levels using cardiac tissue IHC analysis. On the contrary, pretreatment with RHO and CARV alone significantly decreased the cardiac injury markers induced by TIL, inflammatory and anti-inflammatory cytokines, and tissue oxidative-antioxidant parameters. INF-γ, COX-2, OGG1, BAX, and caspase-3 mRNA were downregulated, as observed by real-time PCR, while SOD and Bcl-2 mRNA were upregulated. Furthermore, the CaMKII and α-SMA genes' immune reactivities were significantly decreased in the RHO-pretreated rats.

Method Development and Stability Indicating Studies of Marbofloxacin a Promising Antibiotic for Veterinary Use

This comprehensive review focuses on stability-indicating studies and method development validation for the estimation of Marbofloxacin, a widely used antibiotic in veterinary medicine. The stability-indicating studies assess thebehavior of Marbofloxacin drug degradation under various conditions of stress, while method development validation ensures the reliability and accuracy of analytical methods used to quantify Marbofloxacin as tablet formulations. This review provides a detailed analysis of the key aspects involved in stability-indicating studies & method development validation for its estimation

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.

Analysis of Aminoglycoside Antibiotics: A Challenge in Food Control.

Aminoglycosides are a widely used group of antibiotics in veterinary medicine. However, misuse and abuse of these drugs can lead to residues in the edible tissues of animals. Due to the toxicity of aminoglycosides and the exposure of consumers to the emergence of drug resistance, new methods are being sought to determine aminoglycosides in food. The method presented in this manuscript describes the determination of twelve aminoglycosides (streptomycin, dihydrostreptomycin, spectinomycin, neomycin, gentamicin, hygromycin, paromomycin, kanamycin, tobramycin, amikacin, apramycin, and sisomycin) in thirteen matrices (muscle, kidney, liver, fat, sausages, shrimps, fish honey, milk, eggs, whey powder, sour cream, and curd). Aminoglycosides were isolated from samples with extraction buffer (10 mM NH4OOCH3, 0.4 mM Na2EDTA, 1% NaCl, 2% TCA). For the clean-up purpose, HLB cartridges were used. Analysis was performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) with a Poroshell analytical column and a mobile phase of acetonitrile and heptafluorobutyric acid. The method was validated according to Commission Regulation (EU) 2021/808 requirements. Good performance characteristics were obtained for recovery, linearity, precision, specificity, and decision limits (CCα). This simple and high-sensitivity method can determine multi-aminoglycosides in various food samples for confirmatory analysis.

Catalytic ozonation process using modified activated carbon as a cataly s t for the removal of sarafloxacin antibiotic from aqueous solutions

Sarafloxacin (SAR) is an antibiotic from the fluoroquinolone group and is also one of the most widely used antibiotics in veterinary medicine. Potential performance and appropriate effectiveness have made SAR a special place among antibiotics. Antibiotic residues in the environment cause many problems, the most important of which is antibiotic resistance. Therefore, it is necessary to remove antibiotic residues from the environment. Response surface methodology (RSM) was utilized as a mathematics and statistics approach to optimize the removal efficiency of SAR using the catalytic ozonation process. The obtained regression equation for the response was the quadratic mathematical model. The coefficient of determination (R2), adjusted R2, and predicted R2 were obtained at 0.9939, 0.9917, and 0.9855, respectively. The maximum removal efficiency of 99.3% was obtained under optimum conditions, including a SAR concentration of 30.0 mg L-1, ozone dose of 1.5 mg min-1, catalyst dose (modified activated carbon) of 600 mg L-1, pH of 5.0, and reaction time of 30 min. According to the obtained results, the catalytic ozonation process as a suitable technique can efficiently remove SAR and other pharmaceutical compounds.

Alternatives to antibiotics in veterinary medicine: considerations for the management of Johne's disease.

Antibiotic resistance has become a major health concern globally, with current predictions expecting deaths related to resistant infections to surpass those of cancer by 2050. Major efforts are being undertaken to develop derivative and novel alternatives to current antibiotic therapies in human medicine. What appears to be lacking however, are similar efforts into researching the application of those alternatives, such as (bacterio)phage therapy, in veterinary contexts. Agriculture is still undoubtedly the most prominent consumer of antibiotics, with up to 70% of annual antibiotic usage attributed to this sector, despite policies to reduce their use in food animals. This not only increases the risk of resistant infections spreading from farm to community but also the risk that animals may acquire species-specific infections that subvert treatment. While these diseases may not directly affect human welfare, they greatly affect the profit margin of industries reliant on livestock due to the cost of treatments and (more frequently) the losses associated with animal death. This means actively combatting animal infection not only benefits animal welfare but also global economies. In particular, targeting recurring or chronic conditions associated with certain livestock has the potential to greatly reduce financial losses. This can be achieved by developing novel diagnostics to quickly identify ill animals alongside the design of novel therapies. To explore this concept further, this review employs Johne's disease, a chronic gastroenteritis condition that affects ruminants, as a case study to exemplify the benefits of rapid diagnostics and effective treatment of chronic disease, with particular regard to the diagnostic and therapeutic potential of phage.

European regulations on the use of antibiotics in veterinary medicine

Antimicrobial resistance endangers the successful combat of bacterial infections in humans and animals. The common use of antibiotic classes including those of high clinical value in human as well as veterinary medicine is a critical factor contributing to or suspected to promote the emergence of antibiotic resistance. New legal provisions laid down in veterinary drug legislations and related guidelines and advice are in force in the European Union to safeguard the effectiveness, accessibility and availability of antibiotics.Categorisation of antibiotics in classes of importance for treatment of infections of humans by the WHO was one of the first steps. This task is also undertaken for antibiotics for treatment of animals by the EMA's Antimicrobial Advice Ad Hoc Expert Group. The new veterinary Regulation (EU) 2019/6 has extended restrictions for use of some antibiotics in animals to a full ban of certain antibiotics. While some (but not all) antibiotic compounds not being authorized in veterinary medicine may still be used in companion animals more strict provisions were already applicable for treatment of food producing animal species. Distinct regulations are in place for the treatment of animals kept in large numbers in flocks. Initial regulations focussed on the protection of consumers from residues of veterinary drugs in food commodities, new regulations address prudent (not routinely) and responsible selection, prescription and use of antibiotics, and have improved the practicality for cascade use outside the terms of marketing authorisation. Mandatory recording of use of veterinary medicinal products for food safety reasons is extended to rules for veterinarians and owners or holders of animals to regularly report the use of antibiotics for the purpose of official surveillance of consumption. National sales data of antibiotic veterinary medicinal products have been collected on a voluntary basis until 2022 by ESVAC, which has created awareness of major differences between EU member states. A significant decline in sales was reported for third and fourth generation cephalosporines, polymyxins (colistin), and (fluoro)quinolones since the initiation in 2011.

Antibiotics in veterinary medicine: contamination of livestock production

The safety of raw materials and food is one of the most important tasks in ensuring human safety. Food could be contaminated by veterinary drugs. Antibiotics and some their transformation products residues not only cause direct harm for the consumers health, such as allergic reactions, but also contribute the antibiotic resistance development. Recent methods in the analysis of antibiotics allow to investigate their distribution, accumulation and degradation in water, soil, plants, organs and tissues, as well as to determine their residues in food and raw materials at the maximum permissible levels. This work concerns the characteristics of the main groups antibacterial drugs used for the prevention and treatment of infectious animals’ diseases and the analysis of their identification in animal products (milk and dairy products, eggs, honey, meat and meat products) in 2020-2021 using high-performance liquid chromatography with mass spectrometric detection. Universal approaches in the sample preparation and antibiotics determination assist the analysis time reducing, while ensuring its accuracy, and in addition, increase the range of identified potentially dangerous pollutants. The analysis of the antibiotic’s residues identification above maximum permissible levels showed that the highest percentage is reported for quinolones (41.1%). Groups of antibiotics with minimal contamination risk include aminoglycosides, pleuromutilins and cephalosporins. The data obtained are considered in risk-based approach of planning, sampling and analysis evaluation within the framework of food safety monitoring carried out by the Rosselkhoznadzor.

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.

Colistin Use in European Livestock: Veterinary Field Data on Trends and Perspectives for Further Reduction.

Polymyxin E (colistin) is a medically important active substance both in human and veterinary medicine. Colistin has been used in veterinary medicine since the 1950s. Due to the discovery of the plasmid-borne mcr gene in 2015 and the simultaneously increased importance in human medicine as a last-resort antibiotic, the use of colistin for animals was scrutinised. Though veterinary colistin sales dropped by 76.5% between 2011 to 2020, few studies evaluated real-world data on the use patterns of colistin in different European countries and sectors. A survey among veterinarians revealed that 51.9% did not use or ceased colistin, 33.4% decreased their use, 10.4% stabilised their use, and 2.7% increased use. The most important indications for colistin use were gastrointestinal diseases in pigs followed by septicaemia in poultry. A total of 106 (16.0%) responding veterinarians reported governmental/industry restrictions regarding colistin use, most commonly mentioning "use only after susceptibility testing" (57%). In brief, colistin was perceived as an essential last-resort antibiotic in veterinary medicine for E. coli infections in pigs and poultry, where there is no alternative legal, safe, and efficacious antimicrobial available. To further reduce the need for colistin, synergistic preventive measures, including improved biosecurity, husbandry, and vaccinations, must be employed.

Insights into the impact of manure on the environmental antibiotic residues and resistance pool.

The intensive use of antibiotics in the veterinary sector, linked to the application of manure-derived amendments in agriculture, translates into increased environmental levels of chemical residues, AR bacteria (ARB) and antibiotic resistance genes (ARG). The aim of this review was to evaluate the current evidence regarding the impact of animal farming and manure application on the antibiotic resistance pool in the environment. Several studies reported correlations between the prevalence of clinically relevant ARB and the amount and classes of antibiotics used in animal farming (high resistance rates being reported for medically important antibiotics such as penicillins, tetracyclines, sulfonamides and fluoroquinolones). However, the results are difficult to compare, due to the diversity of the used antimicrobials quantification techniques and to the different amounts and types of antibiotics, exhibiting various degradation times, given in animal feed in different countries. The soils fertilized with manure-derived products harbor a higher and chronic abundance of ARB, multiple ARG and an enriched associated mobilome, which is also sometimes seen in the crops grown on the amended soils. Different manure processing techniques have various efficiencies in the removal of antibiotic residues, ARB and ARGs, but there is only a small amount of data from commercial farms. The efficiency of sludge anaerobic digestion appears to be dependent on the microbial communities composition, the ARB/ARG and operating temperature (mesophilic vs. thermophilic conditions). Composting seems to reduce or eliminate most of antibiotics residues, enteric bacteria, ARB and different representative ARG in manure more rapidly and effectively than lagoon storage. Our review highlights that despite the body of research accumulated in the last years, there are still important knowledge gaps regarding the contribution of manure to the AMR emergence, accumulation, spread and risk of human exposure in countries with high clinical resistance rates. Land microbiome before and after manure application, efficiency of different manure treatment techniques in decreasing the AMR levels in the natural environments and along the food chain must be investigated in depth, covering different geographical regions and countries and using harmonized methodologies. The support of stakeholders is required for the development of specific best practices for prudent – cautious use of antibiotics on farm animals. The use of human reserve antibiotics in veterinary medicine and of unprescribed animal antimicrobials should be stopped and the use of antibiotics on farms must be limited. This integrated approach is needed to determine the optimal conditions for the removal of antibiotic residues, ARB and ARG, to formulate specific recommendations for livestock manure treatment, storage and handling procedures and to translate them into practical on-farm management decisions, to ultimately prevent exposure of human population.

Oxytetracycline Persistence in Uterine Secretion after Intrauterine Administration in Cows with Metritis.

Simple SummaryPuerperal metritis in cows involves the acute inflammation of the uterus, which is often treated with antibacterial drugs. Restrictions on the use of antibiotics in veterinary medicine require the very precise selection of an antibiotic based on its pharmacokinetics and on sensitivity tests of pathogenic bacteria. This study aimed to evaluate the changes in oxytetracycline levels in uterine secretion over time after intrauterine administration in cows with metritis in relation to the sensitivity of pathogenic bacterial isolates. The concentrations of oxytetracycline in the uterine secretions were higher than the minimum inhibitory concentrations against pathogenic bacteria, provoking the infection of the uterus. Higher concentrations were measured in milk rather than in plasma. The intrauterine infusion of oxytetracycline for three consecutive days led to the alleviation of the inflammation and the restoration of the estrus cycle in cows. The local intrauterine administration of oxytetracycline requires the monitoring of the withdrawal time of milk to ensure consumer safety.Puerperal metritis in cows is often treated with antibacterial drugs. The prudent use of antibiotics in farm animals requires state-of-the-art knowledge of their pharmacokinetics and data from sensitivity tests of pathogenic bacteria. Changes in oxytetracycline levels in the uterine secretion over time after intrauterine administration in cows with metritis were evaluated in relation to the sensitivity of pathogenic bacterial isolates. Oxytetracycline levels in plasma, milk and uterine secretion were determined via LC–MS/MS analysis. Pathogenic bacteria were isolated and their sensitivity to oxytetracycline was determined. The concentrations of oxytetracycline in the uterine secretion were 433.79 (39.17–1668.76) µg·mL−1 six hours after the third application at a dose of 8 mg/kg and 84.33 (1.58–467.55) µg·mL−1 96 h after the last treatment. These levels were higher than the minimum inhibitory concentrations—namely, between 4 and 64 µg·mL−1—against pathogenic isolates Trueperella pyogenes, Streptococcus intermedius, Escherichia coli and Bacillus pumilis. Higher concentrations over time were measured in milk rather than in plasma, indicating the need to monitor the withdrawal time for milk. The intrauterine infusion of oxytetracycline for three consecutive days resulted in the successful treatment of metritis in terms alleviating inflammation and restoring the estrus cycle in cows.