A randomised, non-inferiority trial of a new cephalonium dry-cow therapy

AIM: To test the non-inferiority of a novel cephalonium formulation of antibiotic dry-cow therapy (DCT) to a reference formulation, infused at the end of lactation, for cure of existing and prevention of new intramammary infections (IMI). METHODS: Cows with a maximum somatic cell count (SCC) of <= 150,000 cells/ml and with no history of clinical mastitis in the preceding lactation were blocked by herd and age, ranked on maximum SCC, and assigned to be treated with nothing (negative control; n=293 cows), infused in all four quarters with 250 mg of a novel cephalonium formulation (new treatment; n=299 cows), or infused in all four quarters with a reference cephalonium formulation (reference treatment; n=301 cows) at the end of lactation (prophylactic study). Cows with a maximum SCC >150,000 cells/ml and/or with a history of clinical mastitis were blocked as above, and assigned to the new treatment (n=389 cows), or the reference treatment (n=399 cows) in all four quarters (therapeutic study). Quarter-milk samples were collected for bacteriology and measurement of SCC at dryingoff, between 0 and 6 days, and between 3 and 12 days after calving. Non-inferiority was assessed by calculating the difference between the new and reference treatments, and constructing a 95% confidence around this difference. If the upper (or lower) 95% CI was below (or above) the pre-stated margin of non-inferiority the new treatment was declared non-inferior. The pre-stated margins were 3% and 10% for the prophylactic and therapeutic studies, respectively. RESULTS: There was no difference in the proportion of new IMI across the dry period, the hazard of clinical mastitis in the dry period or in the first 21 days of the subsequent lactation, or in the SCC at the quarter or cow level for cows treated with the novel or reference cephalonium formulations in the prophylactic study. Both formulations resulted in fewer new IMI, and lower hazard of clinical mastitis and SCC compared with the negative controls. The new treatment was non-inferior to the reference treatment (p<0.05). In the therapeutic study, the novel formulation resulted in a 2.7% lower percentage cured than the reference formation, but the new treatment was non-inferior to the reference treatment (p<0.05). CONCLUSION: The new treatment was non-inferior to the reference treatment in prevention of new IMI and in curing existing infections over the dry period.