|dc.description.abstract||The objectives of the studies presented herein were to investigate the prevalence of bacteremia in dairy cattle with acute puerperal metritis (APM), quantify the expression and activity of Indoleamine-2,3-Dioxygenase (IDO) in cattle with APM, and evaluate the pharmacokinetics of ampicillin trihydrate in healthy post-partum dairy cattle. The overarching goal of these studies was to better assess the systemic effects of APM on dairy cattle, particularly the effect of APM on the expression of pro and anti-inflammatory molecules and how frequently animals with APM become bacteremic. Should cattle with APM exhibit and immunosuppressive phenotype and bacteria regularly colonize the bloodstream in affected cattle, systemic antimicrobials could be better justified. In addition, knowledge of antimicrobial susceptibility of bacteria in the bloodstream would open doors to alternative therapeutic approaches and reduce the use of medically important antimicrobials, such as the cephalosporins, on dairy farms.
First, the prevalence of bacteremia in dairy cattle with APM was investigated in cattle with naturally occurring disease. This study showed that bacteremia was common, occurring in 17 of 32 post-partum dairy cattle, both healthy and with APM. Furthermore, cattle with hyperglobulinemia were 4.7 times more likely to develop bacteremia than cattle with lower serum globulin concentrations. In addition, cattle with basophils in the peripheral circulation were approximately 13 times less likely to be bacteremic than cattle in which basophils were not detected.
Second, the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, and IDO mRNA in cattle with APM were evaluated with RT-qPCR. In addition, the activity of IDO in cattle with APM was evaluated with high performance liquid chromatography (HPLC). These studies showed that cattle with APM had significantly lower expression of IL-1β in PBMCs than healthy controls. Bacteremic cattle tended to have higher levels of expression of both IL-4 and IL-6, a finding consistent with a TH2 polarization.
Lastly, the disposition of ampicillin trihydrate in plasma, milk, endometrial tissue, and lochial fluid using two dosing regimens in healthy post-partum dairy cattle was studied. Intramuscular administration of ampicillin trihydrate did not result in adverse effects in any of the twelve cattle evaluated and showed preferential accumulation in lochial fluid as compared to plasma, milk, and endometrial tissue.||