Some Aspects and Convergence of Human and Veterinary Drug Repositioning.

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with potential for repositioning. Certain business aspects of drug innovation, especially the relevant factors of market exclusivity, are also discussed. Despite the promising potential of drug repositioning for innovation, it remains underutilized, especially in veterinary applications. To change this landscape for mutual benefits of human and veterinary drug innovation, further exploitation of the potency of drug repositioning is necessary through closer cooperation between all stakeholders, academia, industry, pharmaceutical authorities, and innovation policy makers, and the integration of human and veterinary repositioning into a unified innovation space. For this purpose, the establishment of the conceptually new "One Health Drug Repositioning Platform" is proposed. Oncology is one of the disease areas where this platform can significantly support the development of new drugs for human and dog (or other companion animals) anticancer therapies. As an example of the utilization of human and veterinary drugs for veterinary repositioning, the use of COX inhibitors to treat dog cancers is reviewed.

Use of veterinary medicinal products in the Philippines: regulations, impact, challenges, and recommendations.

Agricultural production is a major driver of the Philippine economy. Mass production of animal products, such as livestock and poultry farming, is one of the most prominent players in the field. Filipino farmers use veterinary medicinal products (VMPs) when raising agricultural animals to improve animal growth and prevent diseases. Unfortunately, the extensive use of VMPs, particularly antibiotics, has been linked to drug resistance in animals, particularly antibiotics. Antimicrobial gene products produced in animals due to the prolonged use of VMPs can passed on to humans when they consume animal products. This paper reviews information on the use of VMPs in the Philippines, including the regulations, their impact, challenges, and potential recommendations. The Philippines has existing legislation regulating VMP use. Several agencies were tasked to regulate the use of VMPs, such as the Department of Agriculture, the Department of Health, and the Philippine National Action Plan. Unfortunately, there is a challenge to implementing these regulations, which affects consumers. The unregulated use of VMPs influences the transmission of antibiotic residues from animals to crops to humans. This challenge should be addressed, with more focus on stricter regulation.

Antibiotic quality and use practices amongst dairy farmers and drug retailers in central Kenyan highlands.

Understanding antibiotic use in dairy systems is critical to guide antimicrobial stewardship programs. We investigated antibiotic use practices in small-holder dairy farms, antibiotic quality, and antimicrobial resistance (AMR) awareness among veterinary drug retailers in a mixed farming community in the central Kenyan highlands. Data were collected from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. A scale was developed to measure knowledge about AMR and antibiotic use using item response theory, and regression models were used to evaluate factors associated with antibiotic use and AMR knowledge. The active pharmaceutical ingredient (API) content of 27 antibiotic samples was determined using high-performance liquid chromatography (HPLC). The presence and levels of 11 antibiotic residues in 108 milk samples collected from the study farms were also investigated using liquid chromatography tandem mass spectrometry (LC-MS/MS). Almost all farms (98.8%, n = 244) reported using antibiotics at least once in the last year, mostly for therapeutic reasons (35.5%). The most used antibiotics were tetracycline (30.6%), penicillin (16.7%), and sulfonamide (9.4%), either individually or in combination, and predominantly in the injectable form. Larger farm size (OR = 1.02, p < 0.001) and history of vaccination use (OR = 1.17, p < 0.001) were significantly associated with a higher frequency of antibiotic use. Drug retailers who advised on animal treatments had a significantly higher mean knowledge scores than those who only sold drugs. We found that 44.4% (12/27) of the tested antibiotics did not meet the United States Pharmacopeial test specifications (percentage of label claim). We detected nine antibiotics in milk, including oxytetracycline, sulfamethoxazole, and trimethoprim. However, only three samples exceeded the maximum residue limits set by the Codex Alimentarius Commission. Our findings indicate that antibiotics of poor quality are accessible and used in small-holder dairy systems, which can be found in milk. These results will aid future investigations on how to promote sustainable antibiotic use practices in dairy systems.

Antimicrobial veterinary drug sale pattern in correlation with critically important antimicrobials for human use: A five-year study in Montenegro.

Antimicrobial resistance (AMR) poses a significant threat in veterinary medicine due to the excessive and inappropriate use of antimicrobial agents, compromising the effectiveness of these drugs. To combat AMR, the collection of data on the consumption of antibiotics is paramount, as there is a well-established connection between antibiotic use and AMR in both humans and food-producing animals. Hence, the current study aimed to generate measurable data concerning the sales patterns of antimicrobial drugs used in animal treatment in Montenegro over a five-year period (from 2017 to 2021). Furthermore, the study aimed to compare these sales figures with the overall sales of antimicrobial veterinary medicine products (AMVMPs) during the same period, with particular emphasis on the utilization of critically important antimicrobials (CIAs) for human use. Data on AMVMPs consumption from 2017 to 2021 were expressed in euros and were sourced from the Institute for Medicines and Medical Devices of Montenegro (CInMED) annual reports, complying with the regulatory framework of the Law on Medicines in this country. Research results indicate that the sales of AMVMPs increased from 2017 to peak in 2019, followed by a stable decline of 21.79% in 2021. However, the portion of selected CIAs AMVMPs in total sales experienced a minor decline from 2017 to 2019, followed by a noticeable 6.11% increase from 2019 to 2021. In order to address AMR challenges, these findings emphasize the importance of enhancing surveillance and monitoring of veterinary antimicrobial use, as well as CIAs for human use.

Comparison of whole blood concentrations of oral human generic modified ciclosporin capsules with microemulsified ciclosporin capsules approved for canine atopic dermatitis following a single oral administration to healthy dogs.

BACKGROUND: There have been no comparative bioavailability studies between the microemulsified ciclosporin formulation, approved for the treatment of canine atopic dermatitis (cAD), and the generic modified formulation of ciclosporin for humans. OBJECTIVES: To compare whole blood ciclosporin concentrations of oral generic modified ciclosporin (Treatment A; Teva Pharmaceuticals) and ciclosporin brand Atopica (Treatment B; Elanco Animal Health) in healthy dogs at 1 and 1.5 h following a single oral administration. METHODS: Whole blood concentrations were evaluated at 1 and 1.5 h post-oral administration of treatments A and B in a randomised, blinded, cross-over study with an 8-day wash-out, after a single administration at 4.4-5.3 mg/kg/day in eight healthy, male-castrated research beagle dogs. Ciclosporin blood concentrations were measured through the Auburn University Clinical Pharmacology Laboratory. RESULTS: Ciclosporin blood concentrations were below the detection limit before the start of treatment for both groups. Blood ciclosporin concentrations for Treatment A (median 1192 ng/ml) were significantly higher at 1 h post-oral administration than those for Treatment B (median 499 ng/ml; p = 0.001). However, no significant differences (p = 0.75) in ciclosporin values were observed at 1.5 h post-administration between treatments A (median 945 ng/ml) and B (median 809 ng/ml). CONCLUSIONS AND CLINICAL RELEVANCE: Generic modified ciclosporin achieved higher blood concentrations at 1 h post-administration than Atopica after a single oral administration in healthy dogs; no difference was noted at 1.5 h. Further clinical studies using generic modified ciclosporin in client-owned dogs affected with cAD are advocated to confirm its therapeutic efficacy.

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine Alzheimer's like mediated by inhibition of neuronal apoptotic.

In treating brain diseases, such as canine cognitive dysfunction (CCD), most currently available potent drugs have weak therapeutic efficacy. One of the causes is the inability of the substance to reach the brain in therapeutic quantities. These pharmaceuticals lacked targeted mechanisms for drug delivery, coming about in an elevated drug concentration in imperative organs, which drove to drug harmfulness. In recent years, cell-free treatment (conditioned medium) determined from animal and human stem cells has provided new promise for treating brain diseases, as CM can stimulate the regeneration of neurons and prevent the inflammation and apoptotic of neurons caused by pathology or aging. On the other hand, it is well known that chitosan-hydrogel (CH) is a polymer derived from natural sources. It has been authorized for use in biomedical use because of its uncommon biodegradability, biocompatibility, and mucoadhesive properties. CH modification has been utilized to generate nanoparticles (NPs) for intranasal and intravenous brain targeting. NPs shown upgraded drug take-up to the brain with decreased side impacts due to their drawn out contact time with the nasal mucosa, surface charge, nanosize, and capacity to extend the tight intersections inside the mucosa. Due to the aforementioned distinctive characteristics, developing Chitosan Hydrogel Nanoparticles load with bovine umbilical mesenchymal stem cell conditioned medium is crucial as a new therapeutic strategy for CCD.

Antibiotic prescribing challenges in smallholder poultry.

This focus article has been prepared by Fraser Broadfoot of the Veterinary Medicines Directorate.

[Availability of drugs for the treatment of cats with ocular diseases in Germany - Discrepancy between theory and reality]. / Verfügbarkeit von Medikamenten für die Behandlung von Katzen mit Augenerkrankungen in Deutschland ­ Diskrepanz zwischen Theorie und Wirklichkeit.

OBJECTIVE: Only a few ophthalmologics specifically approved for cats are available on the market leading to frequent use of drugs approved for humans. In Germany, the administration, dispense or prescription of pharmaceuticals is regulated by the pharmaceuticals law ('Arzneimittelgesetz' (AMG)) as well as the regulation concerning pharmacies in veterinary practice ('Verordnung über tierärztliche Hausapotheken' (TÄHAV)). The aim of this study was to collect data concerning the occurrence and frequency of feline eye diseases and to evaluate the frequency of the necessity for extra-label drug use. Evidence-based, optimal treatment schemes were generated and reviewed with regard to their feasibility in Germany. MATERIAL AND METHODS: Data from 876 cats with ocular problems of the "Small Animal Clinic", Freie Universität Berlin as well as a small animal practice in Southern Germany were evaluated (01.01.2015-31.12.2018). Subsequently, the theoretical accessibility for approved agents and/or extra-label drug use in Germany was analyzed. RESULTS: 1198 diagnoses were based on 925 ophthalmic examinations. The most common diseases include conjunctivitis, keratitis, uveitis, hypertensive retinopathy and glaucoma. 885/1198 (73.9 %) of these diseases required treatment, which equates to 722/925 (78.1 %) cases. For all patients, treatment would have been possible according to evidence-based data. In 225/722 (31.2 %) cases, treatment with the pertaining, specifically approved agents would have been possible. Extra-label drug use would have been necessary in 497/722 cases (68.8 %). Of the 497 cases necessitating extra-label use, pharmaceuticals approved for humans would have been available for 481 cases (96.8 %), extra-label use of other veterinary pharmaceuticals would have been possible in 28 cases (5.6 %) and in 60 cases (12.2 %) especially manufactured drugs could have been employed. In a total of 36/722 cases (5 %), optimal care would not have been possible in the context of the current regulatory framework. CONCLUSION: Based on regulations concerning therapeutic necessity, the ophthalmologic therapy of cats in Germany is possible within the regulatory framework. In the present study, 5 % of the patients could not receive optimal medical care. The closure of this gap demands additional approval of veterinary ophthalmic drugs as well as the research and development of novel active agents and veterinary pharmaceuticals.

Administration of spruce bark (Picea abies) extracts in young lambs exhibits anticoccidial effects but reduces milk intake and body weight gain.

BACKGROUND: Eimeria spp. are widespread apicomplexan parasites known to cause coccidiosis in livestock, resulting in reduced animal welfare and productivity, particularly in sheep. The treatment options are limited, and there is an emerging development of resistance against registered pharmaceuticals. Spruce bark is rich in plant secondary metabolites (PSM), such as condensed tannins, which are bioactive compounds previously shown to have antiparasitic activity. Here, we examined the anticoccidial properties of bark extract of Norway spruce (Picea abies) against a field isolate of ovine Eimeria spp. by treating Eimeria-infected pre-ruminant lambs with water-extracted bark daily for 12 days. We hypothesised that the bark extract would reduce the faecal oocyst excretion and, consequently, the severity of diarrhoea. RESULTS: Oral administration of spruce bark extract significantly reduced the excretion of Eimeria oocysts in milk-fed lambs post treatment till the end of the trial 22 days post infection. This difference in oocyst excretion between the treated and the untreated infected animals increased with time. Compared to the untreated and the sham-infected control group, the group treated with bark extract had softer faeces and reduced milk intake during the treatment period. After discontinuing the treatment, the treated animals got a more solid and formed faeces compared to that of the untreated control group, and the milk intake increased to the level of the sham-infected, untreated control group. The bark extract treated animals had a lower body weight and a lower mean daily body weight gain throughout the whole duration of the experiment. CONCLUSIONS: Bark extract from Norway spruce showed marked anticoccidial properties by reducing the faecal oocyst count and associated diarrhoea in young lambs. Simultaneously we experienced detrimental effects of the treatment, displayed as reduced feed intake and daily body weight gain. Therefore, we suggest conducting similar studies with lower bark extract dosage to explore the possibilities of a better trade-off to reduce the negative impact while maintaining the antiparasitic effect.

Veterinary drug therapies used for undesirable behaviours in UK dogs under primary veterinary care.

Undesirable behaviours (UBs) in dogs are common and important issues with serious potential welfare consequences for both the dogs and their owners. This study aimed to investigate the usage of drug therapy for UBs in dogs and assess demographic risk factors for drug-prescribed UBs within the dog population under primary-care veterinary care in the UK in 2013. Dogs receiving drug therapy for UB were identified through the retrospective analysis of anonymised electronic patient records in VetCompass™. Risk factor analysis used multivariable logistic regression modelling. The study population comprised 103,597 dogs under veterinary care in the UK during 2013. There were 413 drug-prescribed UBs recorded among 404 dogs. The prevalence of dogs with at least one UB event treated with a drug in 2013 was 0.4%. Multivariable modelling identified 3 breeds with increased odds of drug-prescribed UB compared with crossbred dogs: Toy Poodle (OR 2.75), Tibetan Terrier (OR 2.68) and Shih-tzu (OR 1.95). Increasing age was associated with increased odds of drug-prescribed UB, with dogs ≥ 12 years showing 3.1 times the odds compared with dogs < 3 years. Neutered males (OR 1.82) and entire males (OR 1.50) had increased odds compared with entire females. The relatively low prevalence of dogs with at least one UB event that was treated with a drug in 2013 could suggest that opportunities for useful psychopharmaceutical intervention in UBs may be being missed in first opinion veterinary practice. While bodyweight was not a significant factor, the 3 individual breeds at higher odds of an UB treated with a behaviour modifying drug all have a relatively low average bodyweight. The current results also support previous research of a male predisposition to UBs and it is possible that this higher risk resulted in the increased likelihood of being prescribed a behaviour modifying drug, regardless of neuter status.

From the other perspective: Behavioural factors associated with UK sheep farmers' attitudes towards antibiotic use and antibiotic resistance.

Research suggests that many sheep farmers continue to carry out traditional antibiotic use practices despite new 'good practice' recommendations. The aim of this study was to group farmers depending on their attitudes around antibiotic use and antibiotic resistance, and determine the behaviours that are associated with the farmers in these groups. In 2017, a flock health survey was sent to British sheep farmers. K-means cluster analysis was used to identify groups of farmers with similar attitudes towards antibiotic use and resistance. A multivariable logistic regression model was built to determine the associations between farmers' past behaviours and their antibiotic attitude group. There were 461 responses. Two groups of farmers were identified based on their antibiotic attitudes. Cluster 1 were defined as the "discordant" group who had positive views of using antibiotics prophylactically and negative views of reducing antibiotic use. Cluster 2 were defined as the "concordant" group who were positive about reducing antibiotic use and had negative views about using antibiotics prophylactically. Using antibiotics in all lambs (OR = 2.689, CI = 1.571, 4.603), using antibiotics in all ewes (OR = 3.388, CI = 1.318, 8.706), always trimming diseased feet over the past three years (OR = 2.487, CI = 1.459, 4.238), not using a computer to record information over the past three years (OR = 1.996, CI = 1.179, 3.381), not changing worming practices over the past three years (OR = 1.879, CI = 1.144, 3.087), and farmers' perceptions that their sheep flock did not make a financial loss in the past three years (OR = 2.088, CI = 1.079, 4.040) were significantly associated with belonging to the discordant group. Talking to their veterinarian about antibiotic use or the frequency of veterinary visits were not associated with antibiotic attitude group. These results suggest that farmers who had attitudes relating to antibiotic use that did not align with current recommendations carried out more traditional practices, which were strengthened by their positive perceptions of profitability.

Establishing defined daily doses (DDDs) for antimicrobial agents used in pigs, cattle and poultry in Japan and comparing them with European DDD values.

Monitoring of antimicrobial use is essential in the management of the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs administered and normalising it by the population at risk of being treated over a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.61 and 0.66 for antimicrobial agents used for pigs and cattle respectively (p<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.

Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics.

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug transporter/enzyme location, abundance, activity, and specificity between dogs and humans. Supplemental material provides an in-depth discussion of certain topics, offering additional critical points to consider. Based upon an assessment of available state-of-the-art information, data gaps were identified. The hope is that this manuscript will encourage the research needed to support an understanding of similarities and differences in human versus canine drug PK.

Unsafe "crossover-use" of chloramphenicol in Uganda: importance of a One Health approach in antimicrobial resistance policy and regulatory action.

Since the introduction of antibiotics into mainstream health care, resistance to these drugs has become a widespread issue that continues to increase worldwide. Policy decisions to mitigate the development of antimicrobial resistance are hampered by the current lack of surveillance data on antibiotic product availability and use in low-income countries. This study collected data on the antibiotics stocked in human (42) and veterinary (21) drug shops in five sub-counties in Luwero district of Uganda. Focus group discussions with drug shop vendors were also employed to explore antibiotic use practices in the community. Focus group participants reported that farmers used human-intended antibiotics for their livestock, and community members obtain animal-intended antibiotics for their own personal human use. Specifically, chloramphenicol products licensed for human use were being administered to Ugandan poultry. Human consumption of chloramphenicol residues through local animal products represents a serious public health concern. By limiting the health sector scope of antimicrobial resistance research to either human or animal antibiotic use, results can falsely inform policy and intervention strategies. Therefore, a One Health approach is required to understand the wider impact of community antibiotic use and improve overall effectiveness of intervention policy and regulatory action.

A randomised controlled trial to reduce highest priority critically important antimicrobial prescription in companion animals.

Robust evidence supporting strategies for companion animal antimicrobial stewardship is limited, despite frequent prescription of highest priority critically important antimicrobials (HPCIA). Here we describe a randomised controlled trial where electronic prescription data were utilised (August 2018-January 2019) to identify above average HPCIA-prescribing practices (n = 60), which were randomly assigned into a control group (CG) and two intervention groups. In March 2019, the light intervention group (LIG) and heavy intervention group (HIG) were notified of their above average status, and were provided with educational material (LIG, HIG), in-depth benchmarking (HIG), and follow-up meetings (HIG). Following notification, follow-up monitoring lasted for eight months (April-November 2019; post-intervention period) for all intervention groups, though HIG practices were able to access further support (i.e., follow-up meetings) for the first six of these months if requested. Post-intervention, in the HIG a 23.5% and 39.0% reduction in canine (0.5% of total consultations, 95% confidence interval, 0.4-0.6, P = 0.04) and feline (4.4%, 3.4-5.3, P < 0.001) HPCIA-prescribing consultations was observed, compared to the CG (dogs: 0.6%, 0.5-0.8; cats: 7.4%, 6.0-8.7). The LIG was associated with a 16.7% reduction in feline HPCIA prescription (6.1% of total consultations, 5.3-7.0, P = 0.03). Therefore, in this trial we have demonstrated effective strategies for reducing veterinary HPCIA prescription.

A Structural Analysis of the FDA Green Book-Approved Veterinary Drugs and Roles in Human Medicine.

The FDA Green Book is a list of all drug products that have been approved by the FDA for use in veterinary medicine. The Green Book, as published, lacks structural information corresponding to approved drugs. To address this gap, we have compiled the structural data for all FDA Green Book drugs approved through the end of 2019. Herein we discuss the relevance of this data set to human drugs in the context of structural classes and physicochemical properties. Analysis reveals that physicochemical properties are highly optimized and consistent with a high probability of favorable drug metabolism and pharmacokinetic properties, including good oral bioavailability for most compounds. We provide a detailed analysis of this data set organized on the basis of structure and function. Slightly over half (51%) of vet drugs are also approved in human medicine. Combination drugs are biologics are also discussed.

Evaluation of the antimicrobial use in pigs in Japan using dosage-based indicators.

The use of antimicrobial agents in food-producing animals may lead to the emergence and spread of antimicrobial resistance in bacteria of animal origin. The use of antimicrobial agents in pigs in 2018 in Japan was evaluated in terms of the weight of active ingredient and number of defined daily doses (DDD), using annual sales data of veterinary antimicrobials sold for use in pigs. In addition, the use of antimicrobial agents in the Japanese pig sector in 2008 to 2017 was evaluated to determine whether or not there were any differences in temporal change pattern by use of different metrics. In 2018, 447 metric tons of active ingredient, corresponding to 77,379 × 106 kg-days (Japanese DDD) and 34,903 × 106 kg-days (European DDD) were sold. The proportion of the sales amount of sulfonamides, trimethoprim and lincosamides to the total sales amount was significantly different depending on the metric used. For most antimicrobial classes, the number of Japanese DDDs was greater than the number of European DDDs. These results indicate that the DDD-based metric, which is more reflective of the selective pressure of antimicrobials, is recommended for use in monitoring the antimicrobial use in pigs in Japan. The differences in the number of Japanese DDDs and European DDDs appear to confirm the need for Japanese DDDs.

Repurposing the Veterinary Antiprotozoal Drug Ronidazole for the Treatment of Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is a principal cause of hospital-acquired infections and fatalities worldwide. The need for new, more potent anticlostridial agents is far from being met. Drug repurposing can be utilized as a rapid and cost-efficient method of drug development. The current study was conducted to evaluate the activity of ronidazole, a veterinary antiprotozoal drug, as a potential treatment for CDI. Ronidazole inhibited the growth of clinical C. difficile isolates (including NAP1 and toxigenic strains) at a very low concentration (0.125 µg/mL) and showed superior killing kinetics compared with metronidazole, an anticlostridial agent from the same chemical category. In addition, ronidazole did not inhibit growth of several commensal organisms naturally present in the human intestine that play a protective role in preventing CDIs. Furthermore, ronidazole was found to be non-toxic to human gut cells and permeated a monolayer of colonic epithelial cells (Caco-2) at a slower rate than metronidazole. Finally, ronidazole outperformed metronidazole when both were tested at a dose of 1 mg/kg daily in a mouse model of CDI. Overall, ronidazole merits further investigation as a potential treatment for CDIs.

Veterinary drug administration in German veal calves: An exploratory study on retrospective data.

The aim of this cross-sectional study was to characterise the usage of antibiotic and non-antibiotic drugs with a withdrawal period in German veal calves in more detail. In Germany, the documentation of the usage of veterinary medicinal products in food producing animals is mandatory. In the German monitoring system antibiotic use in calves under the age of eight months is recorded irrespective of the production type and only some basic measures (50 % and 75 % percentiles of the entire distributions of the treatment frequencies) are published regularly. Within this study 57 farms were included contributing data of 169 veal calf groups with a total of 91,196 individual calves. To assess the drug use the treatment frequency (TF) was calculated. Most treatments were applied in the first weeks after arrival at the farm against respiratory and gastrointestinal disorders, accounting for 65.2 % and 28.6 % of the TF, respectively. Antibiotics account for 91 % of the TF. The antibiotics used most frequently were tetracyclines (35.6 %), beta-lactams (21.9 %), macrolides (12.7 %), sulphonamides (6.0 %) and trimethoprimes (5.3 %). Tetracyclines and polypeptides were administered as group treatments in more than half of the recorded applications. The number of antibiotic group treatments decreased considerably from the first to the second half of the fattening period. Logistic regression analyses revealed no statistically significant association between TF and groups size or mortality. Nevertheless, the results indicate a negative associated between TF and mortality. Concerning non-antibiotics mainly iron compounds, arylpropionic acids, mucolytics and avermectines were applied, accounting for about 5 % of the total TF. The present study provides basic data on antibiotic and non-antibiotic use in German veal calf production.

The Veterinary Immunological Toolbox: Past, Present, and Future.

It is well-recognized that research capability in veterinary species is restricted by a lack of immunological reagents relative to the extensive toolboxes for small rodent biomedical model species and humans. This creates a barrier to the strategic development of disease control solutions for livestock, companion animals and wildlife that not only affects animal health but can affect human health by increasing the risk of transmission of zoonotic pathogens. There have been a number of projects aimed at reducing the capability gaps in the veterinary immunological toolbox, the majority of these focusing on livestock species. Various approaches have been taken to veterinary immunological reagent development across the globe and technological advances in molecular biology and protein biochemistry have accelerated toolbox development. While short-term funding initiatives can address specific gaps in capability, they do not account for long-term sustainability of reagents and databases that requires a different funding model. We review the past, present and future of the veterinary immunological toolbox with specific reference to recent developments discussed at the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) Immune Toolkit Workshop at the 12th International Veterinary Immunology Symposium (IVIS) in Seattle, USA, 16-19 August 2019. The future availability of these reagents is critical to research for improving animal health, responses to infectious pathogens and vaccine design as well as for important analyses of zoonotic pathogens and the animal /human interface for One Health initiatives.