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Warnham, United Kingdom

Potter T.,Royal Veterinary College | Potter T.,Westpoint Veterinary Group | Illambas J.,Royal Veterinary College | Illambas J.,European Service Center | And 3 more authors.
Veterinary Journal | Year: 2013

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration-time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller-Hinton broth (MHB) and calf serum.Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK-PD data established Cmax/MIC ratios of 45.0 and AUC24h/MIC values of 174.7h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK-PD modelling established three levels of growth inhibition: AUC24h/MIC ratios for no reduction, 3 log10 and 4 log10 reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0h for M. haemolytica and 48.6, 64.9 and 74.8h for P. multocida, on average respectively. Inter-strain variability for 3 log10 and 4 log10 reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC90 values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition. © 2012 Elsevier Ltd. Source


Bartram D.J.,Fort Dodge Animal Health | Heasman L.,Westpoint Veterinary Group | Batten C.A.,Institute for Animal Health | Oura C.A.L.,Institute for Animal Health | And 3 more authors.
Cattle Practice | Year: 2010

Groups of cattle and sheep that had received a primary course of vaccination with an inactivated bluetongue virus serotype 8 (BTV-8) vaccine were booster vaccinated 6 or 12 months later with the homologous vaccine or an alternative inactivated BTV-8 vaccine. The neutralising antibody responses in these animals were compared. Antibody titres to the alternative vaccine were significantly higher than to the homologous vaccine (P=0.008) in cattle and there was no significant difference between the antibody responses to alternative and homologous vaccines in sheep (P=0.973). These data indicate that cattle and sheep primed with one inactivated BTV-8 vaccine may be effectively boostered with an alternative commercial inactivated BTV-8 vaccine. Source


Lees P.,The Royal Veterinary College | Pelligand L.,The Royal Veterinary College | Illambas J.,The Royal Veterinary College | Illambas J.,Zoetis Inc. | And 5 more authors.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2015

The antimicrobial properties of amoxicillin were determined for the bovine respiratory tract pathogens, Mannheima haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves were established. Pharmacokinetic (PK)/pharmacodynamic (PD) modelling of the time-kill data, based on the sigmoidal Emax equation, generated parameters for three levels of efficacy, namely bacteriostatic, bactericidal (3log10 reduction) and 4log10 reduction in bacterial counts. For these levels, mean AUC(0-24 h)/MIC serum values for M. haemolytica were 29.1, 57.3 and 71.5 h, respectively, and corresponding values for P. multocida were 28.1, 44.9 and 59.5 h. Amoxicillin PK was determined in calf serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids, after intramuscular administration of a depot formulation at a dosage of 15 mg/kg. Mean residence times were 16.5 (serum), 29.6 (exudate) and 29.0 h (transudate). Based on serum MICs, integration of in vivo PK and in vitro PD data established maximum concentration (Cmax)/MIC ratios of 13.9:1 and 25.2:1, area under concentration-time curve (AUC0-∞)/MIC ratios of 179 and 325 h and T>MIC of 40.3 and 57.6 h for P. multocida and M. haemolytica, respectively. Monte Carlo simulations for a 90% target attainment rate predicted single dose to achieve bacteriostatic and bactericidal actions over 48 h of 17.7 and 28.3 mg/kg (M. haemolytica) and 17.7 and 34.9 mg/kg (P. multocida). © 2015 John Wiley & Sons. Source


Bartram D.J.,Fort Dodge Animal Health | Heasman L.,Westpoint Veterinary Group | Batten C.A.,Institute for Animal Health | Oura C.A.L.,Institute for Animal Health | And 3 more authors.
Veterinary Journal | Year: 2011

Cattle and sheep that had received a primary course of vaccination with an inactivated bluetongue virus serotype 8 (BTV-8) vaccine were booster vaccinated 6 or 12. months later with the homologous vaccine or an alternative inactivated BTV-8 vaccine and neutralising antibody responses were determined. Antibody titres to the alternative vaccine were significantly higher than to the homologous vaccine (P= 0.013) in cattle. There was no significant difference between the antibody responses to alternative and homologous vaccines in sheep. These data indicate that cattle and sheep primed with one inactivated BTV-8 vaccine may be effectively boosted with an alternative commercial inactivated BTV-8 vaccine. © 2010 Elsevier Ltd. Source


Sidhu P.,The Royal Veterinary College | Sidhu P.,Guru Angad Dev Veterinary and Animal Sciences University | Rassouli A.,The Royal Veterinary College | Rassouli A.,University of Tehran | And 7 more authors.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

Florfenicol was administered subcutaneously to 10 calves at a dose of 40 mg/kg. Pharmacokinetic-pharmacodynamic (PK-PD) integration and modelling of the data were undertaken using a tissue cage model, which allowed comparison of microbial growth inhibition profiles in three fluids, serum, exudate and transudate. Terminal half-lives were relatively long, so that florfenicol concentrations were well maintained in all three fluids. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined in vitro for six strains each of the calf pneumonia pathogens, Mannhemia haemolytica and Pasteurella multocida. An PK-PD integration for three serum indices provided mean values for P. multocida and M. haemolytica, respectively, of 12.6 and 10.4 for Cmax/MIC, 183 and 152 h for AUC0-24 h/MIC and 78 and 76 h for T>MIC. Average florfenicol concentrations in serum exceeded 4 × MIC and 1.5 × MIC for the periods 0-24 and 48-72 h, respectively. Ex vivo growth inhibition curves for M. haemolytica and P. multocida demonstrated a rapid (with 8 h of exposure) and marked (6 log10 reduction in bacterial count or greater) killing response, suggesting a concentration-dependent killing action. During 24-h incubation periods, inhibition of growth to a bacteriostatic level or greater was maintained in serum samples collected up to 96 h and in transudate and exudate samples harvested up to 120 h. Based on the sigmoidal Emax relationship, PK-PD modelling of the ex vivo time-kill data provided AUC0-24 h/MIC serum values for three levels of growth inhibition, bacteriostatic, bactericidal and 4 log10 decrease in bacterial count; mean values were, respectively, 8.2, 26.6 and 39.0 h for M. haemolytica and 7.6, 18.1 and 25.0 h for P. multocida. Similar values were obtained for transudate and exudate. Based on pharmacokinetic and PK-PD modelled data obtained in this study and scientific literature values for MIC distributions, Monte Carlo simulations over 100 000 trials were undertaken to predict once daily dosages of florfenicol required to provide 50% and 90% target attainment rates for three levels of growth inhibition, namely, bacteriostasis, bactericidal action and 4 log10 reduction in bacterial count. © 2013 John Wiley & Sons Ltd. Source

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