Background: A new, extended long-acting tilmicosin (TLAe) preparation was tested against intramammary ceftiofur (CEF) using a non-inferiority trial model during dry-cow therapy (DCT) in a farm with high bovine population density and deficient hygiene application. Objectives: To evaluate the possibility that TLAe administered parenterally can achieve noninferiority status compared to CEF administered intramammary for DCT. Methods: Cows were randomly assigned to TLAe (20 mg/kg subcutaneous; n = 53) or CEF (CEF-HCl, 125 mg/quarter; n = 38 cows) treatment groups. California mastitis testing, colonyforming unit assessment (CFU/mL), and number of cases positive for Staphylococcus aureus were quantified before DCT and 7 d after calving. A complete cure was defined as no bacteria isolated; partial cure when CFU/mL ranged from 150 to 700, and cure-failure when CFU/mL was above 700. Results: TLAe and CEF had overall cure rates of 57% and 53% (p > 0.05) and S. aureus cure rates of 77.7% and 25%, respectively (p < 0.05). The pathogens detected at DCT and 7 days after calving were S. aureus (62.71% and 35.55%), Staphylococcus spp. (22.03% and 35.55%), Streptococcus uberis (10.16% and 13.33%), and Escherichia coli (5.08% and 15.55%). Noninferiority and binary logistic regression analyses revealed a lack of difference in overall efficacies of TLAe and CEF. Apart from S. aureus, S. uberis was the predominant pathogen found in both groups. Conclusions This study is the first successful report of parenteral DCT showing comparable efficacy as CEF, the gold-standard. The extended long-term pharmacokinetic activity of TLAe explains these results.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD. Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixinmeglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg). Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC) 0-72 /MIC ratio with enro-R, and enro-C/Al exhibited an AUC 0-72 /MIC smaller, but Cmax/ MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R. Conclusions and Relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount of enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD. Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixinmeglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg). Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC) 0-72 /MIC ratio with enro-R, and enro-C/Al exhibited an AUC 0-72 /MIC smaller, but Cmax/ MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R. Conclusions and Relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount of enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD. Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixinmeglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg). Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC) 0-72 /MIC ratio with enro-R, and enro-C/Al exhibited an AUC 0-72 /MIC smaller, but Cmax/ MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R. Conclusions and Relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount of enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD. Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixinmeglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg). Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC) 0-72 /MIC ratio with enro-R, and enro-C/Al exhibited an AUC 0-72 /MIC smaller, but Cmax/ MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R. Conclusions and Relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount of enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.