Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes

Abstract

The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93.3%, SP=92.6%, and TM=94.0%] and secondary analysis showed no effect of treatment on risk for presence of an IMI at 0 to 6 DIM (LSM: QT=16.5%, SP=14.1%, and TM=16.0%), risk for development of a new IMI between dry-off and 0 to 6 DIM (LSM: QT=14.8%, SP=12.3%, and TM=14.2%), or risk of experiencing a clinical mastitis event between calving and 100 DIM (LSM: QT=5.3%, SP=3.8%, and TM=4.1%). In conclusion, no difference was observed in efficacy among the 3 products evaluated when assessing the aforementioned quarter-level outcomes.

Treatment of Mastitis in Cattle

“…The FDA-approved dosing regimen is 1 tube containing 500 mg ceftiofur Check treatment information and milk and meat withdrawal times with drug manufacturer before prescribing based on this information. 42,44,45,[47][48][49][53][54][55][57][58][59][78][79][80][81][82][83] into each affected quarter at the time of dry off, no later than 30 days before calving. 43 Spectramast DC was approved for use in 2005, and thus the few studies that include ceftiofur hydrochloride as a treatment are more current and may be more generalizable to modern dairy farms in North America.…”

“…The most recent study conducted by Arruda and colleagues reported a cure risk of 89% and a new IMI risk of 14.1%. 42 Some of the available studies compared blanket ADCT to selective ADCT with this formulation, which may provide some insight into expected cure rates but does not allow calculation of NNT. The NNT calculated (2.1) for the 1 negative controlled study would only apply to minor pathogens, including coagulase-negative staphylococci and C bovis.…”

Effect of dry cow therapy on incidence of clinical mastitis, milk yield and composition in crossbred cows

“…All this foregoing discussion indicates that use of DCT either as preventive or curative measure downsized the incidence of mastitis. Further the antibiotic used in the study has been reported to be comparatively more efficient (Pinedo et al, 2012;Arruda et al, 2013) for prevention and control of udder infection. The decreased incidence of clinical mastitis in DCT group might be due to elimination of infections from udder during the dry period, and higher incidence of clinical mastitis in untreated group may be due to some cows acted as a reservoir of pathogen for re-infection in subsequent lactation (Schukken et al, 2003).…”

“…Further Scherpenzeel et al (2014) reported 1.7 times higher incidence of clinical mastitis at quarter level in cows dried off without antibiotic than control. Previous studies reported lower incidence of clinical mastitis (3-6% at quarter level and 10.1-14.2% at cow level) during early lactation in dairy cows treated with DCT (Godden et al, 2003;Gundelach et al, 2011;Arruda et al, 2013;Johnson et al, 2016). Further, meta-analysis study on dry cow therapy indicated that quarters infused with DCT have higher cure risk and lower new IMI risk over the dry period than untreated quarters (Halasa et al, 2009).…”

<b>Impact of subclinical mastitis on milk yield and economic return of dairy cows</b>

“…Mammary quarters were considered to have an intramammary infection (IMI) when quarter milk samples showed isolation of significant bacterial colony numbers as described by ARRUDA et al (2013), with slight modification. Since we plated 0.1 mL of milk, we considered presence of IMI as detection of any pathogen at any level, similar to what was described by DOHOO et al (2011).…”