Synovial pharmacokinetics of tulathromycin, gamithromycin and florfenicol after a single subcutaneous dose in cattle

Background: Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle. Results: Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/− 2 hours, mean t½ 64.9 +/− 20.1 hours and mean AUC0-inf 154.0 +/− 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/− 30.0 hours, and AUC0-inf 6.5 +/− 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/− 10 hours, t½ 109 +/− 53.9 hours, and AUC0-inf 57.6 +/− 28.2 ug h/mL. Conclusions: In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

A graph patrol problem with random attack times

This paper presents a patrol problem, where a patroller traverses a graph through edges to detect potential attacks at nodes. To design a patrol policy, the patroller needs to take into account not only the graph structure, but also the different attack time distributions, as well as different costs incurred due to successful attacks, at different nodes. We consider both random attackers and strategic attackers. A random attacker chooses which node to attack according to a probability distribution known to the patroller. A strategic attacker plays a two-person zero-sum game with the patroller. For each case, we give an exact linear program to compute the optimal solution. Because the linear programs quickly become computationally intractable as the problem size grows, we develop index-based heuristics. In the random-attacker case, our heuristic is optimal when there are two nodes, and in a suitably chosen asymptotic regime. In the strategic-attacker case, our heuristic is optimal when there are two nodes if the attack times are deterministic taking integer values. In our numerical experiments, our heuristic typically achieves within 1% of optimality with computation time orders of magnitude less than what is required to compute the optimal policy

Comparison of the pharmacokinetics of plant-based treatments in milk and plasma of USDA organic dairy cattle with and without mastitis

<p>Organic dairy products are the second largest sector of the organic food market. Organic dairy products come from United States Department of Agriculture (USDA) certified organic dairy cattle that meet USDA organic standards. Organic dairy cattle in the US cannot be treated with antibiotics for mastitis, one of the costliest diseases of dairy cattle, and thus effective alternatives are needed. When any compound (medication or other non-food product) is used in a food producing animal, a withhold time for that compound that meets US Food and Drug Administration (FDA) standards for food safety must be applied to the animal and its products (like milk). However, there are no US FDA products approved for mastitis that maintain USDA certified organic dairy cattle’s organic status. Thus, we studied the pharmacokinetics of 3 compounds (garlic, thymol and carvacrol) used on organic both healthy and mastitic organic dairy cattle. We also used this information to estimate a milk withhold time using methods consistent with US FDA requirements. For thymol intra-mammary and carvacrol intra-mammary or topical administration, all compounds were partially absorbed into the body from the milk or skin. Thymol and carvacrol are measurable in plasma (at 0.0183 and 0.0202 µg/mL, respectively) after intramammary administration with similar elimination half lives of 1.7 h. Milk concentrations of thymol and carvacrol are much higher at 2.958 and 4.487 µg/mL in healthy cattle, respectively. Concentrations are not significantly different in cows with mastitis as compared to those in healthy cows. Despite these compounds being natural products, they should have a withhold time for milk of at least 24 h after administration. For garlic, levels remained below the limit of detection in milk and plasma and thus no withdrawal time appears to be needed for milk.</p