Treatment of mild to moderate clinical bovine mastitis caused by gram-positive bacteria: A noninferiority randomized trial of local penicillin treatment alone or combined with systemic treatment.


Mastitis worldwide is arguably the most important disease of dairy cattle and thus far only cured with antibiotic administration. With antimicrobial resistance (AMR) the focus has shifted to reduce antibiotic treatment with emphasis being put on optimization at herd level and treatment only through evidence-based cases. Currently, an accepted treatment is through a combination of local intra-udder and systemic treatment with penicillin in terms of the bacteriological cure of mild and moderate clinical mastitis cases caused by gram-positive organisms. The question is whether worse results will be obtained with only local treatment. Therefore, the objective of the study by the authors cited was to investigate whether local treatment alone will provide similar results than combination treatment. If so, apart from cost benefits, the obvious benefit will be reduction of AMR associated with mastitis treatment.

In the trial the non-inferiority margin was set at a relative reduction in bacteriological cure of 15% between the two treatment groups to assess the effect of reducing the total antibiotic use by a factor of 16 for each treatment case. Clinical mastitis cases from 12 farms were enrolled in the study. On-farm selection of gram-positive cases was carried out by the farm personnel in consultation with the veterinarian within the first 24 hours after a clinical mastitis case was detected. These cases were allocated to a treatment group, either local or combination. Bacteriological cure was assessed based on the bacterial species identified in the milk sample from the clinical mastitis case, and two follow-up samples collected approximately two and three weeks after treatment was ended. Identification of bacteria was done by MALDI-TOF and non-inferiority was assessed using unadjusted cure rates from a multivariable mixed logistic regression model. Of the 1972 clinical mastitis cases registered, 345 met all criteria for inclusion in the final database.

Streptococcus uberis was the most commonly isolated pathogen. Non-inferiority was demonstrated for both unadjusted and adjusted cure rates. The unadjusted cure rates were 76.8% and 83.1% for the local and combined treatments, respectively. The pathogen and somatic cell count (SCC) before the clinical case had an effect on the efficacy of treatment; thus efficiency treatment protocols will depend on the herd and specific case. The effect of pathogen and SCC on treatment efficacy was similar irrespective of the treatment protocol.

The authors concluded that bacteriological cure of local penicillin treatment for mild and moderate clinical mastitis cases was not inferior to the combination of local and systemic treatment using a 15% non-inferiority margin. This suggests that a potential 16-fold reduction in antimicrobial use per mastitis treatment can be achieved with no adverse effect on cure rate.