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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-04292008-114152 |
| Date | 29 April 2008 |
| Creators | Clark, Christopher Robert |
| Contributors | Singh, Baljit, Dowling, Patricia M., Chirino-Trejo, Manuel, Boison, Joe O., Townsend, Hugh |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-04292008-114152/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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