Background: Recurrent subclinical mastitis (RScM) due to resistant bacteria has low clinical and bacteriological cure rates, often requiring the culling of cows. The sequential intramammary administration of enrofloxacin hydrochloride-dihydrate (enro-C) followed by ceftiofur HCl may be useful for treating these cases. Objectives: This study assessed the bacteriological and clinical cure-efficacies of the sequentially intramammary administration of enro-C, followed by ceftiofur HCl to treat RScM in Holstein/Friesian cows. Methods: This trial was conducted in a herd with a high prevalence of RScM, and 20 Holstein/Friesian cows were included: 45% suffering subclinical mastitis and 38.9% of the mammary quarters affected. Twenty-nine bacterial isolates in vitro resistant to enro-C were obtained (coagulase-negative Staphylococcus spp, 55.2%; Staphylococcus aureus, 27.6%;Escherichia coli, 6.9%; Streptococcus uberis, 6.9%; Corynebacterium bovis, 3.4%). Polymerase chain reaction-isolated the following genes linked to enro-C resistance: chromosomal (gyrA) and plasmid (aac(6')-lb-cr). The treatments were as follows: twice-daily intramammary infusions of enro-C (300 mg/10 mL) for 5 days. Cows clinically considered treatment failures were also treated with intramammary ceftiofur (125 mg/10 mL, twice daily for 5 days. The clinical and bacteriological cure rates were carried out when completing each treatment phase and at 14 and 21 days, aided by a California mastitis test, somatic cell count, and failure to identify the initially causative bacteria. Results: Enro-C achieved 65% clinical and bacteriological cure rates, and 100% cure rates were obtained after the rescue treatment with ceftiofur HCl. Conclusions Outstanding clinical and bacteriological cure rates in cows affected by RScM were achieved with the consecutive intramammary infusions of enro-C, followed by ceftiofur HCl.

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.

Background: Chronic bovine mastitis is linked to biofilm-producing Staphylococcus aureus (bpSa) or Staphylococcus coagulase-negative (bp-Scn). Objectives: Bp-Sa and bp-Scn were treated with intramammary preparations of either enrofloxacin HCl·2H2O-dimethyl-sulfoxide-chitosan (enro-C/DMSO/chitosan) or enro-C alone. Their potential to inhibit and degrade biofilm formation in vitro was also assessed. Methods: Milk samples were obtained from the affected quarters in a herd. Phenotypical and genotypical identifications as biofilm-producing Staphylococcus species were carried out.Enro-C/DMSO/chitosan and enro-C alone were assessed to determine their in vitro efficacy in interfering with biofilm formation and their bactericidal effects. A prolonged eight-day treatment with a twice-daily intramammary insertion of 10 mL of enro-C/DMSO/chitosan or enro-C alone was set to evaluate the clinical and bacteriological cures on day 10 in 15 cows per group and the biofilm-inhibiting ability. Results: Fifty-seven percent of the isolates were identified as Staphylococcus spp., of which 50% were bp-Sa, 46% bp-Scn, and 4% Staphylococcus pseudintermedius. One hundred percent of the S. aureus isolated and 77% of Staphylococcus coagulase-negative were biofilm producers. In both groups, the icaA and icaD biofilm-producing genes were identified. The experimental preparation could inhibit biofilm formation, degrade mature biofilms, and have well-defined microbicidal effects on planktonic and biofilm bacteria. The respective clinical and bacteriological cure rates were 100% and 80% for enro-C/DMSO/chitosan and 41.7% and 25% for enro-C alone. Conclusions Enro-C/DMSO/chitosan eliminates bp-Sa and bp-Scn from cases of chronic bovine mastitis.