Randomized noninferiority trial comparing 2 commercial intramammary antibiotics for the treatment of nonsevere clinical mastitis in dairy cows

Abstract

The purpose was to evaluate 2 intramammary treatments for mild-to-moderate cases of clinical mastitis in a noninferiority comparison. Noninferiority trials are intended to show whether a given treatment, hetacillin potassium, has at least comparable efficacy as the reference treatment, ceftiofur hydrochloride. Treatments can be deemed inferior to the reference treatment by an amount less than the margin of noninferiority, or inconclusive if the confidence interval crosses the margin of noninferiority. Cows with clinical mastitis from 6 farms were considered for enrollment. Using a randomized design, cows with mild or moderate mastitis in 1 quarter were assigned to on-label treatment with either ceftiofur or hetacillin. A total of 596 cows met the criteria needed for continued enrollment. Treatment distribution resulted in 309 cows in the ceftiofur group and 287 cows in the hetacillin group. Mixed regression analysis was performed for the following outcomes: bacteriological cure, pathogen cure, clinical cure, postevent milk production and linear score, and survival to d 30 and 60. Cox proportional hazards analysis was used to describe treatment effect on survival and mastitis risks. Bacteriological cure, defined as absence of causative organism in samples retrieved at d 14 and 21 postmastitis, was similar between groups. No significant statistical differences were found in cure risk, and noninferiority of hetacillin relative to ceftiofur for bacteriological cure was conclusive (hetacillin=67%, ceftiofur=72%). Absence of a pathogen on both follow-up samples designated a cow as a pathogen cure. Pathogen cure was similar between treatment groups and noninferiority of hetacillin relative to ceftiofur was shown (hetacillin=35%, ceftiofur=32%). Clinical cure (hetacillin=68%, ceftiofur=64%), postevent milk production (hetacillin=37.0kg, ceftiofur=38.2kg), and linear scores (hetacillin=3.4, ceftiofur=3.1) were also not statistically different between treatment groups. Noninferiority of hetacillin relative to ceftiofur was shown for survival to d 30 and survival to d 60, whereas hetacillin was more likely to have a clinical cure than ceftiofur by d 4. No differences were seen between groups when Cox proportional hazards were performed, neither for exit from the herd in the 60 d following the event nor in the risk for a subsequent mastitis event. These findings can be used to develop farm-specific protocols for clinical mastitis treatment.

Efficacy assessment of an intramammary treatment with a new recrystallized enrofloxacin vs ceftiofur and parenteral enrofloxacin in dairy cows with nonsevere clinical mastitis

“…A statistically significant difference in clinical cure in favor of treatments with enro‐C as compared to treatments with ceftiofur HCl or parenteral enrofloxacin was obtained ( p < .05). Clinical cure achieved with ceftiofur in this study is similar to previously reported ones, that is, 64%–65% (Schukken et al., ; Vasquez et al., ), and they also use ceftiofur as gold standard. However, clinical cure of IMI treated with parenteral administration of enrofloxacin (5 mg/kg) has been reported as low (8%–21%) recorded on the third day after treatment (Persson, Katholm, Landin, & Mörk, ; Suojala et al., ).…”

“…It is important to emphasize that the lack of statistical significance when comparing bacteriological cure among groups was due to a reduced number of samples with clearly characterized pathogen isolation. This event is not unique to this trial as many other studies reveal that this situation is a trend (Lago, Godden, Bey, Ruegg, & Leslie, ; Pinzón‐Sánchez & Ruegg, ; Vasquez et al., ). Thus, although no significant differences were found in the probability of bacteriological cure between treatments ( p > .05), a clear trend can be distinguished in favor of both groups treated with enro‐C.…”

“…Exclusion of severe cases of mastitis in this trial aimed at evaluating the efficacy of the drug itself, eliminating the effects of other drugs, also recommended as support therapy for severe cases of mastitis (Erskine et al., ). Other authors testing efficacy of a given treatment against mastitis avoid inclusion of severe cases of this disease (Schukken et al., ; Vasquez et al., ). Also, this article was not designed to assess the environmental impact of using enrofloxacin through the intramammary route.…”

“…As a 1.5% suspension, enro‐C displays a pH of 6‐6.2, and it does not irritate the mammary gland when intramammary administered, and it achieves high concentrations in milk (Martínez‐Cortés, Gutierrez, Tapia, Ocampo, & Sumano, ). These features were the impetus to carry out a clinical trial to compare the efficacy of an intramammary treatment with enro‐C vs. a gold standard intramammary treatment in USA, that is, ceftiofur HCL (Schukken et al., ; Vasquez et al., ), and also compared with the administration of enrofloxacin after its intramuscular (IM) administration. This was thought to minimize the biological variability that accompanies more complicated cases of bovine mastitis.…”

Imidazolidinones and Imidazolidine‐2,4‐diones as Antiviral Agents

“…In addition, organic chemists appreciate them for their use as chiral catalysts. [13,14] Drug molecules featuring a4 -imidazolidinone ring ( Figure 3) include hetacillin( antibacterial), [15,16] spiperone (antipsychotic), [17,18] and spiroxatrine (for the treatment of neurologicald isorders). inhibitors, [7] or b 3 adrenergic receptor agonists.…”