Veterinary drug supply to subsistence and emerging farming communities in the Madikwe District, North West Province, South Africa

Veterinary Needs Appraisals have indicated that there is a need for improved supply of veterinary medicinal products to subsistence and emerging farmers in South Africa. No studies have been conducted to describe and assess the adequacy of the current routes and methods of supply of veterinary medicinal products to these farmers. A combination of focus groups, self-administered questionnaires and direct observations was used to collect information for the purpose of describing and understanding the situation regarding the supply of veterinary medicinal products to the farmers of the Madikwe district. A combination of semi-structured interviews, questionnaires and direct observation was used to gather information. The results indicated that the routes and methods of supply of veterinary medicinal products to the farmers of the Madikwe district were inadequate. The annual sales from outlets within the Madikwe district were poor, with a total of 396 units sold over a period of one year, although there were approximately 2000 farmers in the Madikwe district who were potential clients for these outlets. The majority of products sold by these outlets were ectoparasiticides, followed by Tetracycline antibiotics. The outlets within the Madikwe district were unable to supply vaccines, as they did not have adequate facilities for the storage of these thermolabile products. Farmers had to travel an average of 70 km if they wished to purchase veterinary medicinal products from farmers' co-operatives and pharmacies in larger towns outside the Madikwe district. The routes and methods of supply did not ensure correct storage, and safe and effective use of veterinary medicinal products. Several examples of misuse and incorrect storage and handling of veterinary medicinal products were discovered. Inadequate information transfer, inaccessibility of outlets, poor reliability and quality of outlets and poor service were discovered as reasons for the inadequacy of the routes and methods of supply. Wider distribution of veterinary medicinal products is required but a higher level of control is needed to ensure that products of an acceptable quality are sold. Information and advice must be disseminated together with products.Dissertation (MMedVet (Pharmacology))--University of Pretoria, 2001.Paraclinical Sciencesunrestricte

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

Limitations of MIC as sole metric of pharmacodynamic response across the range of antimicrobial susceptibilities within a single bacterial species

Citation: Wen, X. S., Gehring, R., Stallbaumer, A., Riviere, J. E., & Volkova, V. V. (2016). Limitations of MIC as sole metric of pharmacodynamic response across the range of antimicrobial susceptibilities within a single bacterial species. Scientific Reports, 6, 8. https://doi.org/10.1038/srep37907The minimum inhibitory concentration (MIC) of an antimicrobial drug for a bacterial pathogen is used as a measure of the bacterial susceptibility to the drug. However, relationships between the antimicrobial concentration, bacterial susceptibility, and the pharmacodynamic (PD) inhibitory effect on the bacterial population are more complex. The relationships can be captured by multi-parameter models such as the E-max model. In this study, time-kill experiments were conducted with a zoonotic pathogen Pasteurella multocida and the fluoroquinolone enrofloxacin. Pasteurella multocida isolates with enrofloxacin MIC of 0.01 mu g/mL, 1.5 mu g/mL, and 2.0 mu g/mL were used. An additive inhibitory E-max model was fitted to the data on bacterial population growth inhibition at different enrofloxacin concentrations. The values of PD parameters such as maximal growth inhibition, concentration achieving a half of the maximal inhibition, and Hill coefficient that captures steepness of the relationships between the concentration and effect, varied between the isolate with low MIC and less susceptible isolates. While enrofloxacin PD against the isolate with low MIC exhibited the expected concentration-dependent characteristics, the PD against the less susceptible isolates demonstrated time-dependent characteristics. The results demonstrate that bacterial antimicrobial susceptibility may need to be described by a combination of parameters rather than a single parameter of the MIC

Prednisolone in Dogs—Plasma Exposure and White Blood Cell Response

Glucocorticoids such as prednisolone are commonly used in dogs but there is sparse quantitative pharmacokinetic and pharmacodynamic information of this drug in this species. The objective of this study was to quantitatively characterize the concentration-effect relationship for prednisolone in dogs on neutrophil and lymphocyte trafficking and cortisol suppression. Nine beagles, 2–12 years old and part of a group for teaching/research were used in a 4-way crossover experiment including two treatments, active or placebo, administered either per os (PO) or intravenously (IV). Plasma was analyzed for prednisolone and cortisol using ultra-high performance liquid chromatography – tandem mass spectrometry. Leucocyte counts were performed in whole blood. Data was then analyzed by non-linear mixed effect modeling to estimate pharmacokinetic and pharmacodynamic parameters. After administration of prednisolone sodium succinate IV, the typical value (between subject variation) for total body prednisolone clearance was 1,370 ml/h·kg (13.4%). The volumes of the central and peripheral compartment were 2,300 ml/kg (10.7%) and 600 ml/kg (16.0%), respectively. The terminal plasma half-life was 1.7 h. The prednisolone plasma concentration producing 50% of the maximum response was 10 ng/mL (90.3%), 22.5 ng/ml (52.3%) and 0.04 ng/mL (197.3%) for neutrophil, lymphocyte and cortisol response, respectively. The administered dose (1 mg/kg) increased neutrophil and decreased lymphocyte numbers but not over the entire dosage interval of 24 h, due to the short half-life. However, glucocorticoids have a wide range of responses. An anti-inflammatory response due to altered gene transcription might have a longer duration. Future studies on the anti-inflammatory potency together with data presented are needed to optimize future dosage recommendations in dogs

Plasma atropine concentrations associated with decreased intestinal motility in horses

IntroductionAtropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methodsEight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. ResultsAtropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg center dot h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 mu g/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. ConclusionThe IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 mu l of 1% atropine sulfate per drop or less may be used to lower the risk further

A study to examine the relationship between uterine pathology and depletion of oxytetracycline in plasma and milk after intrauterine infusion

Citation: Gorden, P. J., Ydstie, J., Kleinhenz, M. D., Wulf, L. W., Gehring, R., Wang, C., & Coetzee, J. F. (2016). A study to examine the relationship between uterine pathology and depletion of oxytetracycline in plasma and milk after intrauterine infusion. Journal of Animal Science, 94, 30-30. doi:10.2527/msasas2016-065Metritis is a frequent problem in postpartum dairy cows. Intrauterine therapy with oxytetracycline (OTC) is often used to improve therapeutic outcomes, although efficacy data supporting this therapy are ambiguous. Several manuscripts describe the depletion of OTC from milk following intrauterine therapy. However, none of these studies have correlated uterine severity scores with milk OTC concentrations using highly sensitive detection systems. Our objective was to do this to test the hypothesis that cows with more severe uterine severity would have higher OTC residues in milk following intrauterine therapy. Thirty-two cows received a single treatment of 4 g of OTC via intrauterine infusion. Blood and milk samples were collected before intrauterine therapy and throughout the trial period of 96 h after infusion. Uterine severity scores were assigned at initiation of therapy and every 24 h throughout the remainder of the trial. Plasma and milk samples were analyzed for OTC concentrations using liquid chromatography coupled with mass spectrometry. Following treatment, OTC rapidly diffused from the uterus to plasma and from plasma to milk. Maximum concentration in plasma and milk occurred within 24 h following intrauterine infusion and 18 of the cows still had detectable levels of OTC in milk 4 d after intrauterine infusion. Greater uterine severity score at the initiation of treatment showed a significant positively correlation with higher milk OTC concentration at the second milking following treatment (R2 = 0.46, P = 0.01) but there was no correlation between initial uterine severity score and OTC concentration at the conclusion of the study (R2 = ?0.06, P = 0.75). In the United States, intrauterine administration of OTC is considered to be an extra-label therapy. The use of uterine severity score can be used to predict OTC concentration in the first day following therapy but should not be used as a predictor of OTC concentrations 96 h after treatment. Dairy producers should consult with their veterinarian to develop strategies that will prevent the presence of violative residues of OTC in bulk tank milk following intrauterine therapy