Negatively controlled, randomized clinical trial comparing different antimicrobial interventions for treatment of clinical mastitis caused by gram-positive pathogens

Abstract

The general objective of this study was to evaluate the effect of 3 intramammary antibiotic interventions using 2 commercially available antibiotics with narrowor broad-spectrum activity on cure rates of clinical mastitis (CM) caused by gram-positive bacteria. We also compared the efficacy of treatment protocols, including a negative control, on outcomes at the cow and mammary quarter level. Before the onset of the study, 5,987 animals more than 12 mo old were randomly preassigned to 1 of 4 protocols in the event of grampositive CM (except for Staphylococcus aureus and Trueperella pyogenes) during lactation: 3 infusions with 62.5 mg of amoxicillin performed 12 h apart (AMOX-L); 5 infusions once a day with 62.5 mg of amoxicillin (AMOX-EL); 5 infusions once a day with 125 mg of ceftiofur hydrochloride (CEFT-L); or negative control, no treatment performed until 5 d after diagnosis (NEG-CTR). Randomization was performed to preassign 90% of cows to one of the antibiotic protocols (30% in each group) and 10% to the negative control. A total of 696 quarter cases of CM met the inclusion criteria and were evaluated in the study. Quarter-level outcomes were assessed based on 5 milk samples collected up to 14 ± 3 d following enrollment (i.e., first day of treatment), whereas variables at the cow level [composite somatic cell count (SCC), milk production, and survival in the herd] were assessed up to 90 d after CM diagnosis. Streptococcus uberis, followed by Streptococcus dysgalactiae, were the main causes of gram-positive CM. Overall, clinical cure was higher for CEFT-L than for AMOX-EL, and no difference was observed between CEFT-L and AMOX-L. Likewise, no significant differences were detected on overall bacteriological cure, although some treatment effects were observed at the species level. Compared with antibiotic-treated groups, quarters assigned to NEG-CTR had higher counts of colony-forming units (cfu), 16S rRNA gene copy numbers, and Streptococcus relative abundance (RA) until d 5 after enrollment. Quarters treated with AMOX-L had higher cfu counts on d 5, 8, and 14 after enrollment compared with the other antibiotic protocols. In addition, the RA of Streptococcus spp. was higher on d 14 after enrollment for AMOX-treated quarters compared with the CEFT-L group. Linear score of SCC was higher for AMOX-treated cows than for CEFT-L in the first test day after CM. However, cows assigned to AMOX-L had higher milk production than those submitted to the AMOX-EL and CEFT-L protocols. In conclusion, the 2-d protocol with 3 intramammary infusions of amoxicillin (narrow-spectrum antimicrobial) had similar overall clinical and bacteriological cures as 5 administrations (once a day) with ceftiofur hydrochloride (wide spectrum). No significant difference was observed on CM recurrence and cow survival. However, quarters treated with 5-d protocols were more effective at reducing milk cfu counts than quarters in the AMOX-L protocol. In addition, lower Streptococcus spp. RA was observed in ceftiofur-treated quarters compared with the...

Therapy of Subclinical Mastitis during Lactation

“…However, a more recent study found no difference in bacterial cure rate between clinical mastitis cases assigned to three intramammary infusions at 12-hourly intervals compared with five infusions at 12-hourly intervals with amoxicillin clavulanic acid [17]. Similarly, similar bacteriological cure rates and similar survival rates were found following 3 × 12 hourly amoxicillin, 5 × 24 hourly amoxicillin or 5 × 24 hourly ceftiofur intramammary treatments of Gram-positive clinical mastitis cases [18].…”

Whole-genome sequencing reveals high genetic diversity of Streptococcus uberis isolated from cows with mastitis

“…Strains were identified in a contemporary clinical trial evaluating the efficacy of four protocols for treatment of clinical mastitis caused by Gram-positive pathogens [ 46 ]. Briefly, all clinical mastitis cases identified on the farm had two milk samples collected using aseptic methods.…”

“…In this step, analysis of total Gram-positive bacteria count was performed using the technique of Agar droplets [ 47 ] using a selective and differential culture medium (Accutreat®, FERA Diagnostics and Biologicals,, Ithaca, NY). Results of bacterial counts are published elsewhere [ 46 ]. A single colony was selected from the aforementioned culture plate and streaked onto a CHROMagar Streptococcus base (CHROMagar, France) plate followed by incubation overnight at 37 °C.…”

“…The cows were treated with antibiotics within 48 h after CM identification. As our study was performed contemporarily with another study [ 48 ], cows identified with Gram-positive mastitis were randomly allocated to three treatment groups: amoxicillin (label use), 3 infusions with 62.5 mg of amoxicillin (Amoxi-Mast, Merck Animal Health, Millsboro, DE) performed at 12 ± 2 h apart; amoxicillin (extra-label), 5 infusions once a day with 62.5 mg of amoxicillin (Amoxi-Mast, Merck Animal Health); or ceftiofur (label use), 5 infusions once a day with 125 mg of ceftiofur hydrochloride (Spectramast, Zoetis, Kalamazoo, MI) [ 46 ].…”

“…A quarter loss was defined as the loss of mammary quarter physiological function due to the damage caused by the mastitis case. And the culling or death of cows was based on the farm records up to 90 days of CM diagnosis [ 46 ].…”