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.

2015-03-01·Journal of Dairy Science1区 · 农林科学

Short communication: Pharmacokinetics of intramammary hetacillin in dairy cattle milked 3 times per day

1区 · 农林科学

Article

作者: Lindquist, Danielle A ; Baynes, Ronald E ; Smith, Geof W

Mastitis remains a critical disease in the dairy industry and the use of intramammary antibiotics plays a critical role in mastitis treatment. Hetacillin is currently approved as an intramammary antibiotic that is used to treat mastitis in dairy cows. It is approved for once a day administration and can be used for a total of 3 d. An increasing number of dairy farms are milking 3 times per day (instead of the traditional 2 times per day) and very little pharmacokinetic data exists on the use of intramammary drugs in a 3×system. The primary purpose of this study was to determine if once a day intramammary infusion of hetacillin is sufficient to maintain therapeutic drug concentrations in cattle milked 3 times per day. Eight Holstein cattle milked 3 times per day were used in this study. After collecting a baseline milk sample, each cow received intramammary infusions of hetacillin in the left front and right rear quarters once a day for 3 d. Milk samples from each of the treated quarters were collected at each milking and frozen until analysis. Milk samples were analyzed for ampicillin concentrations using an ultra-performance liquid chromatography method. All treated quarters had antibiotic concentrations well above the minimum inhibitory concentration (MIC) for gram-positive mastitis pathogens at 8 and 16 h postinfusion. Milk concentrations had fallen well below the MIC by the 24-h period (before the next infusion). All 8 cows in this study consistently had individual quarter milk ampicillin concentrations below the FDA tolerance of 0.01 μg/mL (10 ppb) within 48 h of the last infusion. Based on this study, milk ampicillin concentrations exceed the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC90) for at least 65% of the dosing interval, which is sufficient for once-daily dosing with most cases of gram-positive mastitis. Therefore, intramammary hetacillin should be an effective treatment for the vast majority of gram-positive mastitis pathogens when used according to label (once per day) in cows milked 3 times per day.

2014-09-01·Journal of Dairy Science1区 · 农林科学

Treatments of clinical mastitis occurring in cows on 51 large dairy herds in Wisconsin

1区 · 农林科学

Article

作者: Ruegg, P L ; Oliveira, L

Antimicrobials are frequently used for treatment of bovine mastitis and few studies have examined modern treatment strategies on large US dairy farms. The objective of this study was to describe treatment practices for clinical mastitis occurring in cows on large dairy herds in Wisconsin. Treatments performed on 747 cows experiencing cases of mild, moderate, or severe symptoms of clinical mastitis were recorded on 51 Wisconsin dairy farms. Duplicate milk samples were collected from the affected quarter for microbiological analysis at the onset of clinical mastitis and 14 to 21 d after treatment ended. Cows were treated according to individual farm protocol. Drugs and doses used for treatments were recorded for each case. Among all herds, 5 intramammary (IMM) antimicrobials (amoxicillin, hetacillin, pirlimycin, ceftiofur, and cephapirin) were used to treat cows for clinical mastitis. Of 712 cows with complete treatment data, 71.6% were treated with IMM ceftiofur either solely or combined with other antimicrobials (administered either IMM or systemically). Of cows experiencing severe symptoms of clinical mastitis, 43.8% received IMM treatment concurrent with systemic antimicrobials. Of all cows treated, 23.1% received an additional secondary treatment (either IMM, systemic, or both) because of perceived lack of response to the initial treatment. The majority of IMM treatments were administered to cows with a microbiological diagnosis of no growth (34.9%) or Escherichia coli (27.2%). Half of the cows experiencing cases caused by E. coli were treated using systemic antimicrobials in contrast to only 6.8% of cows experiencing cases caused by coagulase-negative staphylococci. In conflict with FDA regulations, which do not allow extra-label treatments using sulfonamides, a total of 22 cows from 8 farms were treated with systemic sulfadimethoxine either solely or in combination with oxytetracycline. Antimicrobial drugs were used on all herds and many cows received extra-label treatments. Great opportunity exists to improve mastitis therapy on large dairy herds, but use of more diagnostic methodologies is necessary to guide treatments. Farmers and veterinarians should work together to create protocols based on the herd needs considering reduced inappropriate and excessive use of antimicrobials.

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