Noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows

Abstract

The objective of this study was to evaluate the noninferiority of 2 intramammary treatments for nonsevere clinical mastitis. The 2 treatments were a first-generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third-generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d). A total of 296 cases on 7 farms met the enrollment criteria for the study. Streptococcus dysgalactiae was the most common bacterial species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or ceftiofur hydrochloride via intramammary infusion according to label standards. Bacteriological cure was defined based on 2 posttreatment milk samples taken at 10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur was shown for bacteriological cure of gram-positive cases and for clinical cure of all cases. Ceftiofur showed a significantly higher bacteriological cure in gram-negative cases. Treatments showed no significant difference in bacteriological cure of all cases and in time to exit from the study, where the absence of a difference does not imply noninferiority. Based on the findings from this study, farm-specific treatment protocols that differ for gram-positive and gram-negative cased may be developed.

Diversity and health status specific fluctuations of intrauterine microbial communities in postpartum dairy cows

“…S1). S. uberis, the major causative agent of bovine mastitis (Schukken et al, 2013), was found to be the most prevalent member of the genus Streptococcus and, interestingly, more than half of the Bacillus spp. isolates belonged to the species B. pumilus and 23% to B. licheniformis.…”

Treatment of Mastitis in Cattle

“…Similar results were obtained during a clinical trial in New York conducted in 2010 and 2011, which enrolled 296 cases of mastitis from 7 farms milking 357 to 1578 cows. 11 In that study, the most commonly isolated pathogen was Streptococcus dysgalactiae, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella species.…”

“…36 The drug was evaluated at 2 dose levels; data for the approved tube dose of 125 mg cephapirin are reported here. Ceftiofur was also a treatment in the 2013 study 11 described in the section about cephapirin and in an earlier study that focused on Gram-negative pathogens:…”

“…"Noninferiority Trial Comparing a First-Generation Cephalosporin with a ThirdGeneration Cephalosporin in the Treatment of Nonsevere Clinical Mastitis in Dairy Cows" by Schukken and colleagues11 Case definition: abnormal milk with or without signs of inflammation in the udder…”

Longitudinal metagenomic profiling of bovine milk to assess the impact of intramammary treatment using a third-generation cephalosporin

“…. Although current guidelines do not recommend the use of intramammary antibiotics for cows diagnosed with Gram-negative mastitis314, improved bacteriological and clinical outcomes have been shown in mastitic cows treated with third-generation cephalosporins compared with other antimicrobials or untreated controls1516. However, the impact of these broad-spectrum antibiotics on the milk microbiota (other than major pathogens) remains unknown.…”