Master of Science / Department of Clinical Sciences / Daniel U. Thomson / Bovine Respiratory Disease (BRD) continues to be one of the largest animal health concerns in the cattle industry. BRD is a multifaceted group of pathogens, both viral and bacterial, that take advantage of an immune compromised calf to cause disease. This study took aim at comparing metaphylactic treatments for BRD in both the feedlot and pasture setting. In the feedlot study, heifers (n=579, 403.7 ± 27.4 lbs) from Southwest Texas were identified as being high risk for BRD and shipped to the Clayton Livestock Research Center in Clayton, NM. Cattle were randomly allocated within truck load lots into 18 to 20 head treatment pens (30 pens; 3 treatments; 10 reps). Cattle were given one of three metaphylactic treatments based on the randomly assigned treatment for their pen within a replicate. The three antibiotic treatments administered at initial processing were: 1) Tulathromycin (2.5 mg/kg), 2) Tilmicosin (13.3 mg/kg), and 3) Gamithromycin (6.0 mg/kg). Cattle were fed a typical commercial starter diet for the first 56-60 d with a step-up ration change at day 28. At the end of the feeding period, pens were weighed and body weights recorded. Dry Matter Intake, morbidity, and mortality were recorded by CLRC personnel daily. Cattle administered tulathromycin had higher daily gains than cattle administered gamithromycin by 0.29 lbs/d (P<.01) and tended (P=0.09) have higher daily gains than cattle that received tilmicosin by 0.18 lbs/d. Tulathromycin treated cattle tended (P = 0.12) to have improved feed efficiency compared to gamithromycin treated cattle. Cattle that received tulathromycin (5.2%) had lower morbidity rates (P < .02) than tilmicosin (14.6%) and gamithromycin (12.79%) treated cattle. There were no treatment differences in dry matter intake or mortality in cattle. For the wheat pasture study, heifers (n=120, 393.2 ± 28.6 lbs) from the same origin and risk were shipped to the CLRC and processed before being trailed to a nearby wheat pasture. Cattle were randomly assigned into three treatment groups (3 treatments, 40 reps), and were given one of three metaphylactic treatments. The three antibiotic treatments administered at initial processing were: 1) Tulathromycin (2.5 mg/kg), 2) Tilmicosin (13.3 mg/kg), and 3) Gamithromycin (6.0 mg/kg). Cattle were allowed to graze on wheat for 54 days with free-choice Hi-Pro mineral mixed with Lasalocid, an ionophore. After 54 days on wheat pasture, the cattle were trailed back to the CLRC facilities and final individual weights were recorded. Morbidity and mortality were recorded daily by CLRC personnel. No differences were identified for ADG (P=0.98), morbidity (P=0.46) or mortality (P=0.36) among the three treatment groups.

Doctor of Philosophy / Diagnostic Medicine/Pathobiology / Michael D. Apley / Bovine respiratory disease (BRD) remains a major disease in beef production systems. The administration of antimicrobials for both the control and treatment of acute BRD is common. According to most published accounts, antimicrobial resistance among BRD pathogens is increasing; therefore, judicious antimicrobial usage is vital for continued efficacy. The introduction of a novel antimicrobial class has not occurred for well over a decade, therefore it is paramount to maximize efficacy of the antimicrobials currently available. The challenge is targeting the perfect scenario: maximizing clinical efficacy while minimizing antimicrobial resistance. The host-pathogen-drug interaction is very complex and despite current sophisticated technology, this interaction is still not well understood for many infectious diseases. This dissertation work sought to investigate the effects of the administration of a macrolide for both control and treatment of acute BRD on the prevalence of resistance among isolated Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Whole genome sequencing of M. haemolytica was utilized to investigate the presence/absence of macrolide resistance genes and their relationship to the observed minimum inhibitory concentration. Cattle were sampled (plasma and pulmonary epithelial lining fluid) after administration of gamithromycin for drug concentration analysis. A non-linear mixed effects approach was used to fit a compartmental model to the resulting sparse pharmacokinetic data so that a complete time concentration curve could be simulated. From these curves, the CMAX and AUC were measured and used to calculate standard PKPD indices using the MIC values of the isolated bacteria. Clear associations between the use of gamithromycin for control and treatment of BRD and a statistically significantly increased likelihood of macrolide resistance were not found, possibly due to sample size limitations. The calculation of pharmacokinetic-pharmacodynamic indices found that a longer drug exposure was more closely associated with a successful treatment outcome, but there was not a statistically significant correlation. However, there were few clinical failures in this study giving further credence to the complexity of the in vivo system. There are many factors beyond pharmacokinetics/pharmacodynamics and MICs that contribute to the success of a treatment regimen for cattle suffering from BRD.