The potential use of the macrolide antimicrobial tilmicosin in the horse was assessed by initially reviewing bacterial isolates from equine infections. This demonstrated that respiratory disease due to Gram positive organisms was the most common bacterial infection documented at WCVM. Furthermore, 45% of Streptococcus zooepidemicus isolates were resistant to the commonly used potentiated sulphonamides. <p>It was necessary to first develop and validate a robust HPLC analytical technique to detect tilmicosin in a variety of equine tissues. The methodology was fully validated in plasma and lung with LODs of 13 ng/mL and 181 ng/g respectively.<p>In a preliminary trial, we administered tilmicosin to recently weaned foals at a dose of 4 mg/kg PO sid or 10 mg/kg SC q 72 hrs. The oral dose did not result in detectable tissue concentrations of tilmicosin. The pharmacokinetics of the injectable dose were similar to previous reports in other species. The injectable preparation resulted in severe swelling at the site of injection associated with edema and tissue necrosis. Otherwise, tilmicosin was well tolerated by the foals and no foals developed severe colitis. However, a semi-quantitative fecal bacteriological technique demonstrated marked changes in the normal fecal flora, with profound overgrowth of the Enterbacteriacae and almost complete removal of the normal â-hemolytic streptococci population. No known pathogens were isolated from the feces.<p>In a subsequent study, we investigated the administration of higher doses of oral tilmicosin to unweaned foals to simulate treatment of R. equi. A dose of 40 mg/kg PO sid resulted in detectable plasma concentrations of tilmicosin. Foals were treated at this dose regimen for 2 weeks and sequentially euthanized. Tissue analysis demonstrated concentrations of tilmicosin in tissues similar to those seen with the 10 mg/kg sc dose with a Cmax of 4 µg/g in lung and a MRT which was shorter at 8.8 hrs. The MIC50 of R. equi to tilmicosin was 4 µg/g. Based on pharmacodynamic studies it appears that oral tilmicosin has the potential to be of use in the treatment of R. equi pneumonia in foals. No adverse clinical effects were noted in the foals; however, the fecal flora was again changed by tilmicosin administration. <p>The fecal flora of the unweaned foals was different from that of the older animals with almost no â-haemolytic streptococci and a predominantly Gram negative flora. Disruption of the fecal flora did result in overgrowth of Cl. perfringens which was not associated with disease.<p>In a final study, we compared the effects of tilmicosin and ceftiofur on the fecal flora of adult horses. The fecal flora of the horses receiving tilmicosin was severely disrupted in the same manner as the weaned foals with the added effect of overgrowth of Cl. perfringens. Ceftiofur which is widely regarded as being associated with antimicrobial associated diarrhea had very little effect on the fecal flora.<p>It is concluded that oral tilmicosin shows potential for the treatment of R. equi pneumonia in young foals. However, care should be taken due to possibility of developing colitis. The drugs use should be avoided in older horses due to the very real risk of developing acute bacterial colitis. The injectable preparation should not be used in horses due to the severity of the reaction at the injection site.

The potential use of the macrolide antimicrobial tilmicosin in the horse was assessed by initially reviewing bacterial isolates from equine infections. This demonstrated that respiratory disease due to Gram positive organisms was the most common bacterial infection documented at WCVM. Furthermore, 45% of Streptococcus zooepidemicus isolates were resistant to the commonly used potentiated sulphonamides. <p>It was necessary to first develop and validate a robust HPLC analytical technique to detect tilmicosin in a variety of equine tissues. The methodology was fully validated in plasma and lung with LODs of 13 ng/mL and 181 ng/g respectively.<p>In a preliminary trial, we administered tilmicosin to recently weaned foals at a dose of 4 mg/kg PO sid or 10 mg/kg SC q 72 hrs. The oral dose did not result in detectable tissue concentrations of tilmicosin. The pharmacokinetics of the injectable dose were similar to previous reports in other species. The injectable preparation resulted in severe swelling at the site of injection associated with edema and tissue necrosis. Otherwise, tilmicosin was well tolerated by the foals and no foals developed severe colitis. However, a semi-quantitative fecal bacteriological technique demonstrated marked changes in the normal fecal flora, with profound overgrowth of the Enterbacteriacae and almost complete removal of the normal â-hemolytic streptococci population. No known pathogens were isolated from the feces.<p>In a subsequent study, we investigated the administration of higher doses of oral tilmicosin to unweaned foals to simulate treatment of R. equi. A dose of 40 mg/kg PO sid resulted in detectable plasma concentrations of tilmicosin. Foals were treated at this dose regimen for 2 weeks and sequentially euthanized. Tissue analysis demonstrated concentrations of tilmicosin in tissues similar to those seen with the 10 mg/kg sc dose with a Cmax of 4 µg/g in lung and a MRT which was shorter at 8.8 hrs. The MIC50 of R. equi to tilmicosin was 4 µg/g. Based on pharmacodynamic studies it appears that oral tilmicosin has the potential to be of use in the treatment of R. equi pneumonia in foals. No adverse clinical effects were noted in the foals; however, the fecal flora was again changed by tilmicosin administration. <p>The fecal flora of the unweaned foals was different from that of the older animals with almost no â-haemolytic streptococci and a predominantly Gram negative flora. Disruption of the fecal flora did result in overgrowth of Cl. perfringens which was not associated with disease.<p>In a final study, we compared the effects of tilmicosin and ceftiofur on the fecal flora of adult horses. The fecal flora of the horses receiving tilmicosin was severely disrupted in the same manner as the weaned foals with the added effect of overgrowth of Cl. perfringens. Ceftiofur which is widely regarded as being associated with antimicrobial associated diarrhea had very little effect on the fecal flora.<p>It is concluded that oral tilmicosin shows potential for the treatment of R. equi pneumonia in young foals. However, care should be taken due to possibility of developing colitis. The drugs use should be avoided in older horses due to the very real risk of developing acute bacterial colitis. The injectable preparation should not be used in horses due to the severity of the reaction at the injection site.

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.