Comparison between intrauterine application of an antibiotic and an herbal product to treat clinical endometritis in dairy cattle - A randomized multicentre field study.

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis. Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis. In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923). In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis.

Estimation of epidemiological cut-off values for eight antibiotics used for treatment of bovine mastitis caused by Streptococcus uberis and Streptococcus dysgalactiae subsp. dysgalactiae.

Interpretive criteria for antimicrobial susceptibility testing are lacking for most antimicrobials used for bovine streptococcal mastitis. The objectives of this study were to determine (tentative) epidemiological cut-off ((T)ECOFF) values for clinically relevant antibiotics used for treatment of bovine mastitis, and to estimate the proportion of acquired resistance (non-wild-types) in Streptococcus dysgalactiae subsp. dysgalactiae and Streptococcus uberis. A total of 255 S. uberis and 231 S. dysgalactiae subsp. dysgalactiae isolates were obtained in Denmark and Norway from bovine mastitis. The isolates were tested for susceptibility to 10 antibiotics using broth microdilution. In accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard operating procedure, additional published MIC distributions were included for the estimation of ECOFFs for cloxacillin, cephapirin, lincomycin and tylosin, and TECOFFs for amoxicillin, benzylpenicillin, cephapirin and oxytetracycline. The proportion of non-wild-type (NWT) isolates for the beta-lactams was significantly higher in the Danish S. uberis (45-55%) compared to the Norwegian isolates (10-13%). For oxytetracycline, the proportion of NWT was significantly higher in the Danish isolates, both for S. uberis (28% vs. 3%) and S. dysgalactiae (22% vs. 0%). A bridging study testing in parallel MICs in a subset of isolates (n = 83) with the CLSI-specified and the EUCAST-specified broths showed excellent correlation between the MICs obtained with the two methods. The new ECOFFs and TECOFFs proposed in this study can be used for surveillance of antimicrobial resistance, and - for antimicrobials licensed for streptococcal bovine mastitis - as surrogate clinical breakpoints for predicting their clinical efficacy for this indication.

Prevalence of subclinical endometritis in dairy cows that recovered after treatment of clinical endometritis with cephapirin and PGF2α.

The aims of our study were to evaluate (1) the prevalence of subclinical endometritis (SE) in clinically cured cows after treatment of clinical endometritis (CE) with uterine cephapirin infusion or with systemic application of PGF2α and after self-healing, (2) the prevalence of SE in clinically cured cows in relation to the type of vaginal discharge. The study was conducted on 222 Polish Holstein Friesian cows with CE diagnosed by vaginoscopy and ultrasound. The animals were randomly allocated to one of three groups: Group 1 (n = 72): intrauterine cephapirin infusion; Group 2 (n = 73): single intramuscular injection of dinoprost; and Group 3 (n = 77): left untreated as a control. All cows were reexamined two weeks later (Exam 1). If there was still CE at this examination, these cows were treated using the same method as previously and were examined 2 weeks later (Exam 2). Cows still having CE at the second examination were examined two weeks later (Exam 3). Cows without signs of CE at Exams 1, 2 and 3 were considered cured, and endometrial samples from the uteri were collected by cytobrush to diagnose SE using cytological evaluation of PMN percentage. The threshold for SE was set at ≥ 5% PMNs. Two cows each from Groups 1 and 3 and three cows from Group 2 were not clinically recovered at Exam 3 and were excluded from the analysis. In total, SE was diagnosed in an average of 40.9% of clinically cured cows. The prevalence of SE in Group 1, 2 and 3 was 35.0%, 47.1% and 40.0%, respectively (p > 0.05). There were significantly higher (p < 0.05) SE cases after treatment of CE associated with purulent vaginal discharge than with mucopurulent discharge. In relation to the method of treatment, the prevalence of SE was significantly higher (p < 0.05) in cows treated with cephapirin with purulent vaginal discharge than with mucopurulent vaginal discharge. In conclusion, the study showed a high prevalence of SE in cows clinically cured after treatment of clinical endometritis with cephapirin or PGF2α and after self-healing. The prevalence of SE was significantly higher in cows with purulent vaginal discharge than with mucopurulent vaginal discharge. Therefore, in cows clinically recovered from clinical endometritis, the prevalence of SE should always be considered a negative consequence, and the resulting management of this uterine disease should be implemented at the herd level.

Randomized noninferiority field trial evaluating cephapirin sodium for treatment of nonsevere clinical mastitis.

The general objective of this study was to evaluate whether cephapirin sodium is noninferior compared with a positive control broad-spectrum product formulated with a combination of antimicrobials for intramammary treatment of nonsevere clinical mastitis. In addition, we compared the efficacy of treatments on the cure risks of pathogen groups (gram-positive, gram-negative, and cultures with no growth) based on culture results. A total of 346 cows distributed in 31 commercial dairy herds were selected to participate in the study, although only 236 met the criteria for evaluation of microbiological cure. Coagulase-negative staphylococci were the most isolated gram-positive pathogens in pretreatment milk samples, whereas the most common gram-negative bacterium was Escherichia coli. Cows attending the postadmission criteria were treated with 4 intramammary infusions (12 h apart) of one of the following antimicrobials: 300 mg of cephapirin sodium + 20 mg of prednisolone (CS), or the positive control treatment formulated with a combination of antimicrobials (200 mg of tetracycline + 250 mg of neomycin + 28 mg of bacitracin + 10 mg of prednisolone; TNB). Noninferiority analysis and mixed regression models (overall and considering the pathogen groups) were performed for the following outcomes: bacteriological cure (absence of the causative pathogens in cultures performed in milk samples collected at 14 and 21 ± 3 d after enrollment), pathogen cure (absence of any pathogen on both follow-up samples), clinical cure (absence of clinical sign in the milk and mammary gland at 48 h after the last antimicrobial infusion), extended clinical cure (normal milk and normal gland on the second posttreatment sample collection (d 21), and linear score of somatic cell count cure [linear score of somatic cell count recovery (≤4.0) on d 21 ± 3 after enrollment]. No significant differences were observed between treatments regarding any of the evaluated outcomes in both regression models (overall and considering the pathogen groups). Noninferiority of CS relative to TNB was inconclusive for bacteriological cure (CS = 0.68; TNB = 0.73) and clinical cure (CS = 0.88; TNB = 0.94), as the confidence intervals crossed the pre-stated margin of noninferiority (Δ = -0.15). Cephapirin sodium was noninferior compared with TNB for pathogen cure (CS = 0.36; TNB = 0.35), extended clinical cure (CS = 0.93; TNB = 0.92), and linear score of somatic cell count cure (CS = 0.29; TNB = 0.28). In conclusion, the use of intramammary CS for treatment of nonsevere clinical mastitis has similar efficacy as a treatment regimen with a combination of antimicrobial agents (tetracycline + neomycin + bacitracin), although noninferiority analysis showed inconclusive results for bacteriological and clinical cures.

In vitro antibiotic susceptibility and biofilm production of Staphylococcus aureus isolates recovered from bovine intramammary infections that persisted or not following extended therapies with cephapirin, pirlimycin or ceftiofur.

Staphylococcus aureus intramammary infections (IMIs) have low cure rates using standard antibiotic treatment and increasing the duration of treatment usually improves therapeutic success. Chronic IMIs are thought to be caused by bacteria presenting a specific virulence phenotype that includes the capacity to produce greater amounts of biofilm. In this study, antibiotic susceptibility and biofilm production by S. aureus isolates recovered from IMIs that were cured or not following an extended therapy with cephapirin, pirlimycin or ceftiofur for 5, 8 and 8 days, respectively, were compared. An isolate was confirmed as from a persistent case (not cured) if the same S. aureus strain was isolated before and after treatment as revealed by the same VNTR profile (variable number of tandem repeats detected by multiplex PCR). The antibiotic minimal inhibitory concentrations (MICs) were determined for these isolates as well as the capacity of the isolates to produce biofilm. Isolates from persistent cases after extended therapy with cephapirin or ceftiofur had higher MICs for these drugs compared to isolates from non-persistent cases (p < 0.05) even though the antibiotic susceptibility breakpoints were not exceeded. Isolates of the ceftiofur study significantly increased their biofilm production in presence of a sub-MIC of ceftiofur (p < 0.05), whereas isolates from the pirlimycin group produced significantly less biofilm in presence of a sub-MIC of pirlimycin (p < 0.001). Relative antibiotic susceptibility of the isolates as well as biofilm production may play a role in the failure of extended therapies. On the other hand, some antibiotics may counteract biofilm formation and improve cure rates.

Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd.

The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7-3.7) as was odds of survival to 60 d (odds ratio = 1.4; 95% confidence interval: 0.7-2.6). The one significant difference found for the effect of treatment was in hospital days; pathogen-based cows experienced, on average, 3 fewer days than blanket therapy cows. A majority (68.5%) of moderate and mild clinical cases would not have been treated if all cows on this trial were enrolled in a pathogen-based protocol. The use of a strategic treatment protocol based on 24-h postmastitis pathogen results has potential to efficiently reduce antimicrobial use.

Effectiveness of intrauterine treatment with cephapirin in dairy cows with purulent vaginal discharge.

The objective of this study was to assess the efficacy of cephapirin intrauterine treatment preceding a timed artificial insemination protocol in lactating dairy cows with purulent vaginal discharges (PVDs). Holstein dairy cows (n = 1247) from 18 herds were enrolled in a controlled randomized clinical trial. At 34 days in milk (DIM; ±7 days), cows had a genital examination (transrectal palpation, vaginoscopy, and uterine bacteriology). They were randomly assigned to either the control group (CONT, no treatment) or the treatment group (CEPH) consisting of 1 intrauterine infusion of 500-mg cephapirin benzathine (RCL) (Metricure, Merck Animal Health, Montreal, Canada) regardless of the uterine health status. All cows were systematically enrolled in a presynch-ovsynch protocol for the first insemination. A second genital examination was made 2 weeks later. Cows that received any systemic or local antibiotics 10 days prior sampling to the end of the synchronization protocol were excluded from the study. Reproductive data of cows were collected for at least 300 DIM, entered in a databank, and validated (health record management software, DSAHR). Pregnancy diagnosis was done by transrectal palpation at the routinely scheduled veterinarian visits. On the basis of the highest sum of sensibility and specificity for pregnancy status at 120 DIM, the optimal cutoff for vaginal discharge score was determined as the presence of cloudy discharge with or without purulent material (PVD+, score 2). With a prevalence of 21.6% at 34 DIM, PVD+ was detrimental to the first-service conception rate (FSCR; PVD+: 26 ± 5%; PVD-: 40 ± 3%; P = 0.02). The negative effect of PVD+ was indicated by a hazard ratio of 0.72 (chi-square = 8.58; P < 0.01; 95% confidence interval = 0.56-0.91). Treatment with cephapirin was associated with a significant improvement of the FSCR in PVD+ cows (PVD+ CEPH: 36 ± 5%, PVD+ CONT: 23 ± 5%; P < 0.05), although it did not produce a considerable clinical cure based on the second examination. Thus, a longer period of time following treatment may be needed to properly assess the efficacy of intrauterine treatment in PVD+ cows. In conclusion, cephapirin intrauterine treatment in PVD+ cows at 34 DIM considerably improves reproductive performance compared with untreated PVD+ cows.

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

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.

Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.

Clinical mastitis caused by E. coli accounts for significant production losses and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic intervention in mild to moderate cases are incompletely understood. We investigated the effect of intramammary treatment with cefapirin alone or in combination with prednisolone on gene expression profiles in experimentally-induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in another quarter. At 24 h (n = 3) or 48 h (n = 3) post-challenge, tissue samples from control and treated quarters were collected for microarray analysis. Gene expression analysis of challenged, un-treated quarters revealed an up-regulation of transcripts associated with immune response functions compared to un-challenged quarters. Both treatments resulted in down-regulation of these transcripts compared to challenged, un-treated quarters most prominently for genes representing Chemokine and TLR-signaling pathways. Gene expression of Lipopolysaccharide Binding Protein (LBP), CCL2 and CXCL2 were only significantly down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated controls. Down-regulation of chemokines was further confirmed on the basis of protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a significant effect of treatment on cell recruitment with a more pronounced effect in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological clearance, combination therapy may prevent neutrophil-induced tissue damage and promote recovery of the gland.

Pharmacokinetics in foremilk and antimicrobial activity of cephapirin following intramammary administration in healthy and Staphylococcus aureus-infected cows.

AIM: To evaluate the kinetic profile of cephapirin and detect differences in its milk disposition following intramammary administration in healthy, and subclinically Staphylococcus aureus infected, quarters of lactating cows, to assess the minimum inhibitory concentration (MIC) of cephapirin for Staph. aureus field isolates, and to calculate the time during which drug concentrations were above the MIC (T>MIC). METHODS: Five healthy and five Staph. aureus-infected lactating cows received cephapirin at 275 mg/quarter, twice at 12-hour intervals. Foremilk samples were manually collected from individual quarters before treatments and 2, 8, 12 hours after the last drug administration, and then every 12 hours until the tenth milking. Concentrations of cephapirin and desacetyl-cephapirin were measured in milk samples after solid phase extraction and high-performance liquid chromatography analysis. A non-compartmental model was applied to data to obtain pharmacokinetic results. Eleven Staph. aureus isolates from the study-infected quarters and 30 additional isolates from cows in another two farms in the same area were used to determine MIC for cephapirin using the microdilution broth method. RESULTS: Mean maximum drug concentrations were higher in milk from healthy quarters (1334.8 (SD 1322.7) µg/mL) than in the infected ones (234.7 (SD 141.4) µg/mL), but the elimination half-life was longer in the infected (4.8 (SD 1.9) hours) than uninfected (3.3 (SD 0.33) hours) quarters (p<0.05). Mean residence time was comparable in healthy and infected quarters (approximately 8 hours). The amounts of desacetyl-cephapirin recovered in the samples were very low (below 2%). The MIC90 for all field strains of Staph. aureus (n=41) was 0.25 µg/mL. The calculated T>MIC90 was 38 (SD 13), 27 (SD 11) and 35 (SD 8) hours after last treatment in healthy, suspected and infected quarters, respectively. CONCLUSION AND CLINICAL RELEVANCE: The intramammary administration of sodium cephapirin at 275 mg/quarter, twice every 12 hours in lactating cows resulted in higher drug concentrations in milk of quarters with no infection than in the subclinically infected ones. These concentrations were above the MIC90 for 35 hours in infected cows. According to these results intramammary administration of cephapirin at 12-hour intervals during lactation should be potentially effective against Staph. aureus infection, but studies of clinical efficacy are necessary for confirmation.

Noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows.

The objective of this study was to evaluate the noninferiority of 2 intramammary treatments for nonsevere clinical mastitis. The 2 treatments were a first-generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third-generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d). A total of 296 cases on 7 farms met the enrollment criteria for the study. Streptococcus dysgalactiae was the most common bacterial species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or ceftiofur hydrochloride via intramammary infusion according to label standards. Bacteriological cure was defined based on 2 posttreatment milk samples taken at 10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur was shown for bacteriological cure of gram-positive cases and for clinical cure of all cases. Ceftiofur showed a significantly higher bacteriological cure in gram-negative cases. Treatments showed no significant difference in bacteriological cure of all cases and in time to exit from the study, where the absence of a difference does not imply noninferiority. Based on the findings from this study, farm-specific treatment protocols that differ for gram-positive and gram-negative cased may be developed.

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: II. Cow health and performance in early lactation.

The objective of this randomized noninferiority clinical trial was to compare the effect of treatment with 3 different dry cow therapy formulations at dry-off on cow-level health and production parameters in the first 100 d in milk (DIM) in the subsequent lactation, including 305-d mature-equivalent (305 ME) milk production, linear score (LS), risk for the cow experiencing a clinical mastitis event, risk for culling or death, and risk for pregnancy by 100 DIM. A total of 1,091 cows from 6 commercial dairy herds in 4 states (California, Iowa, Minnesota, and Wisconsin) were randomly assigned at dry-off to receive treatment with 1 of 3 commercial products: Quartermaster (QT; Zoetis Animal Health, Madison, NJ), Spectramast DC (SP; Zoetis Animal Health) or ToMorrow Dry Cow (TM; Boehringer Ingelheim Vetmedica Inc., St Joseph, MO). All clinical mastitis, pregnancy, culling, and death events occurring in the first 100 DIM were recorded by farm staff using an on-farm electronic record-keeping system. Dairy Herd Improvement Association test-day records of milk production and milk component testing were retrieved electronically. Mixed linear regression analysis was used to describe the effect of treatment on 305ME milk production and LS recorded on the last Dairy Herd Improvement Association test day before 100 DIM. Cox proportional hazards regression analysis was used to describe the effect of treatment on risk for experiencing a case of clinical mastitis, risk for leaving the herd, and risk for pregnancy between calving and 100 DIM. Results showed no effect of treatment on adjusted mean 305 ME milk production (QT=11,759 kg, SP=11,574 kg, and TM=11,761 kg) or adjusted mean LS (QT=1.8, SP=1.9, and TM=1.6) on the last test day before 100 DIM. Similarly, no effect of treatment was observed on risk for a clinical mastitis event (QT=14.8%, SP=12.7%, and TM=15.0%), risk for leaving the herd (QT=7.5%, SP=9.2%, and TM=10.3%), or risk for pregnancy (QT=31.5%, SP=26.1%, and TM=26.9%) between calving and 100 DIM.

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

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.

A history of acute bacterial meningitis.

Although meningitis was not yet known as such, its symptoms have been conceptualized in different ways and many theories about its causes have been formulated in the course of time. Terms like hydrocephalus and brain fever were used for different clinical manifestations of what today would be recognized as meningitis. Pathological-anatomical findings led to the emergence of the clinical entity from several old concepts of disease. Initially, diagnostic means were limited and therapeutic methods did not differ much from those that had been applied for centuries, even far into the nineteenth century. Discoveries in bacteriology and the introduction of the lumbar puncture provided a new paradigm for knowledge of the pathophysiology and treatment of what then became known with the term meningitis. The development of new therapeutic methods including antiserum, sulfonamides, and penicillin resulted in a decreasing mortality during the past century. Nowadays, with the use of antibiotics, bacterial meningitis can often be cured.

The selective treatment of clinical mastitis based on on-farm culture results: I. Effects on antibiotic use, milk withholding time, and short-term clinical and bacteriological outcomes.

The objective of this multi-state, multi-herd clinical trial was to evaluate the efficacy of using an on-farm culture system to guide strategic treatment decisions in cows with clinical mastitis. The study was conducted in 8 commercial dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and Ontario, Canada. A total of 422 cows affected with mild or moderate clinical mastitis in 449 quarters were randomly assigned to either (1) a positive-control treatment program or (2) an on-farm, culture-based treatment program. Quarter cases assigned to the positive-control group received immediate on-label intramammary treatment with cephapirin sodium. Quarters assigned to the culture-based treatment program were cultured on-farm and treated with cephapirin sodium after 18 to 24h of incubation if they had gram-positive growth or a mixed infection. Quarters with gram-negative or no growth did not receive intramammary therapy. The proportion of quarter cases assigned to positive-control and culture-based treatments that received intramammary antibiotic therapy because of study assignment was 100 and 44%, respectively; the proportion of cases that received secondary antibiotic therapy was 36 and 19%, respectively; and the proportion of cases that received intramammary antibiotic therapy because of study assignment or secondary therapy was 100 and 51%, respectively. A tendency existed for a decrease in the number of days in which milk was discarded from cows assigned to the culture-based treatment program versus cows assigned to the positive-control group (5.9 vs. 5.2 d). No statistically significant differences existed between cases assigned to the positive-control and cases assigned to the culture-based treatment program in days to clinical cure (2.7 vs. 3.2 d), bacteriological cure risk within 21 d of enrollment (71 vs. 60%), new intramammary infection risk within 21 d of enrollment (50 vs. 50%), and treatment failure risk (presence of infection, secondary treatment, clinical mastitis recurrence, or removal from herd within 21 d after enrollment; 81 vs. 78%). In summary, the use of an on-farm culture system to guide the strategic treatment of clinical mastitis reduced intramammary antibiotic use by half and tended to decrease milk withholding time by 1 d, without significant differences in days to clinical cure, bacteriological cure risk, new intramammary infection risk, and treatment failure risk within 21 d after the clinical mastitis event.

The selective treatment of clinical mastitis based on on-farm culture results: II. Effects on lactation performance, including clinical mastitis recurrence, somatic cell count, milk production, and cow survival.

The objective of this multi-state, multi-herd clinical trial was to report on the efficacy of using an on-farm culture system to guide strategic treatment decisions in cows with clinical mastitis. The study was conducted in 8 commercial dairy farms ranging in size from 144 to 1,795 cows from Minnesota, Wisconsin, and Ontario, Canada. A total of 422 cows affected with mild or moderate clinical mastitis in 449 quarters were randomly assigned to either (1) a positive-control treatment program or (2) an on-farm culture-based treatment program. Quarter cases assigned to the positive-control group received immediate on-label intramammary treatment with cephapirin sodium. Quarters assigned to the culture-based treatment program were not treated until the results of on-farm culture were determined after 18 to 24h of incubation. Quarters in the culture-based treatment program that had gram-positive growth or a mixed infection were treated according to label instruction using intramammary cephapirin sodium. Quarters assigned to the culture-based treatment program that had gram-negative or no-growth did not receive intramammary therapy. It was already reported in a companion paper that the selective treatment of clinical mastitis based on on-farm culture results decreases antibiotic use by half and tends to decrease milk withholding time without affecting short-term clinical and bacteriological outcomes. The present article reports on long-term outcomes of the aforementioned study. No statistically significant differences existed between cases assigned to the positive-control program and cases assigned to the culture-based treatment program in risk and days for recurrence of clinical mastitis in the same quarter (35% and 78 d vs. 43% and 82 d), linear somatic cell count (4.2 vs. 4.4), daily milk production (30.0 vs. 30.7 kg), and risk and days for culling or death events (28% and 160 d vs. 32% and 137 d) for the rest of the lactation after enrollment of the clinical mastitis case. In summary, the selective treatment of clinical mastitis based on on-farm culture resulted in no differences in long-term outcomes, such as recurrence of clinical mastitis in the same quarter, somatic cell count, milk production, and cow survival for the rest of the lactation after clinical mastitis.

Partial budgeting assessment of the treatment of pyometra, follicular cysts and ovarian inactivity causing postpartum anoestrus in dairy cattle.

A total of 412 multiparous German Holstein cows were screened for postpartum pyometra, follicular cysts and ovarian inactivity to assess economic and productivity losses in relation to pharmaceutical expenditures. Our results show that cows treated for pyometra with prostaglandin f2 alpha (PGF2α) and oxytetracycline had significantly (P<0.05) greater total and net returns than untreated cows or those treated with PGF2α+cephapirin or PGF2α alone. Milk yields from untreated cows affected by follicular cysts were significantly (P<0.05) lower than the yields from cows treated with gonadotrophin-releasing hormone (GnRH)- and GnRH+PGF2α. In addition, the use of GnRH to treat cows with ovarian inactivity resulted in significantly (P<0.05) lower costs and greater total and net return values compared to untreated controls.

Bacteriological and cytological findings during the late puerperal period after two different treatments of retained placenta followed by acute puerperal metritis.

The aim of the study was to compare the effect of two acute puerperal metritis (APM) treatment protocols on uterine condition during the late puerperal period (5th to 7th week). Late gestation healthy cows (n = 21) were divided randomly in three equal groups. Parturitions were induced. Treatments of APM were started on the third day postpartum (PP). Group A was treated with an oxytocin analogue carbetocin for three days and intrauterine administration of cephapirin between days 15 and 17. Group B was given intramuscular injection of ceftiofur for five days followed by two injections of prostaglandin F2alpha, at an interval of 12 h, on the eighth day PP. Group C served as the control group with no treatment. Body temperature was recorded daily for 14 days PP. Uterine biopsies for bacteriology, and uterobrush samples for cytology, were taken once a week from the 5th to 7th week postpartum. No differences were found in body temperature on day 14 PP, presence of bacteriological infections and disappearance of uterine inflammatory signs diagnosed by cytological examination between experimental groups.