ceftiofur and Mastitis--Bovine

Recurrent subclinical mastitis (RScM) due to resistant bacteria has low clinical and bacteriological cure rates, often requiring the culling of cows. The sequential intra-mammary administration of enrofloxacin hydrochloride-dihydrate (enro-C) followed by ceftiofur HCl may be useful for treating these cases.. This study assessed the bacteriological and clinical cure-efficacies of the sequentially intramammary administration of enro-C, followed by ceftiofur HCl to treat RScM in Holstein/Friesian cows.. Enro-C achieved 65% clinical and bacteriological cure rates, and 100% cure rates were obtained after the rescue treatment with ceftiofur HCl.. Outstanding clinical and bacteriological cure rates in cows affected by RScM were achieved with the consecutive intramammary infusions of enro-C, followed by ceftiofur HCl.

Topics: Animals; Bacterial Infections; Cattle; Cephalosporins; Drug Resistance, Bacterial; Enrofloxacin; Female; Hydrochloric Acid; Mastitis, Bovine; Recurrence

The objective of this study was to compare culture- and algorithm-guided selective dry-cow therapy (SDCT) programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure clinical trial for the following cow-level outcomes: clinical mastitis, removal from the herd, and Dairy Herd Improvement Association (DHIA) test-day milk yield and SCC measures during the first 120 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by only treating quarters from which aseptically collected milk samples tested positive on a rapid culture system after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow met at least one of the following criteria: (1) any DHIA test with a somatic cell count >200,000 cells/mL during the current lactation, and (2) ≥2 clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Clinical mastitis and removal from the herd events (i.e., culling or death) and DHIA test-day data from dry-off to 120 DIM were extracted from herd records. Hazard ratios (HR) for the effect of treatment group on clinical mastitis and removal from the herd during 1 to 120 DIM were determined using Cox proportional hazards regression. The effects of treatment group on test-day log

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Colostrum; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Pregnancy; Proportional Hazards Models

Selective dry-cow therapy (SDCT) could be used to reduce antibiotic use on commercial dairy farms in the United States but is not yet widely adopted, possibly due to concerns about the potential for negative effects on cow health. The objective of this study was to compare culture- and algorithm-guided SDCT programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure, non-inferiority trial for the following quarter-level outcomes: antibiotic use at dry-off, dry period intramammary infection (IMI) cure risk, dry period new IMI risk, and IMI risk at 1 to 13 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by treating only quarters from which aseptically collected milk samples tested positive on the Minnesota Easy 4Cast plate (University of Minnesota, St. Paul, MN) after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow had either a Dairy Herd Improvement Association test somatic cell count >200,000 cells/mL during the current lactation or 2 or more clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Intramammary infection status at enrollment and at 1 to 13 DIM was determined using standard bacteriological methods. The effect of treatment group on dry period IMI cure, dry period new IMI, and IMI risk at 1 to 13 DIM was determined using generalized linear mixed models (logistic), with marginal standardization to derive risk difference (RD) estimates. Quarter-level antibiotic use at dry-off for each group was BDCT (100%), cult-SDCT (45%), and alg-SDCT (45%). The crude dry period IMI cure risk for all quarters was 87.5% (818/935), the crude dry period new IMI risk was 20.1% (764/3,794), and the prevalence of IMI at 1 to 13 DIM was 23% (961/4,173). Non-inferiority analysis indicated that culture- and algorithm-guided SDCT approaches performed at least as well as BDCT for dry period IMI cure risk. In addition, the final models indicated that the risks for each of the 3 IMI measures were similar between all 3 treatment groups (i.e

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Prevalence

A new, extended long-acting tilmicosin (TLAe) preparation was tested against intramammary ceftiofur (CEF) using a non-inferiority trial model during dry-cow therapy (DCT) in a farm with high bovine population density and deficient hygiene application.. To evaluate the possibility that TLAe administered parenterally can achieve non-inferiority status compared to CEF administered intramammary for DCT.. TLAe and CEF had overall cure rates of 57% and 53% (. This study is the first successful report of parenteral DCT showing comparable efficacy as CEF, the gold-standard. The extended long-term pharmacokinetic activity of TLAe explains these results.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Delayed-Action Preparations; Escherichia coli; Escherichia coli Infections; Female; Injections, Subcutaneous; Mastitis, Bovine; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tylosin

The objective of this study was to describe weekly quarter-level somatic cell count (QSCC) after occurrence of nonsevere clinical mastitis (CM) that was diagnosed as culture negative, or caused by Escherichia coli or Klebsiella pneumoniae. All cases occurred in cows enrolled in negatively, controlled randomized clinical trials. We hypothesized that after occurrence of CM, QSCC patterns would vary among etiologies and this effect would not be mitigated by treatment using intramammary (IMM) ceftiofur. Data from two previously published randomized clinical trials performed on 3 Wisconsin dairy farms were used. Only cases confirmed as culture negative (NG) or E. coli or Kleb. pneumoniae (GRAMNEG) were used for analysis. In NG, cows were assigned to no antimicrobial treatment (negative control, n = 44) or 5 d of once daily IMM (n = 41) infusions with an approved product containing ceftiofur hydrochloride. In GRAMNEG, cows were assigned to IMM treatment with the same ceftiofur product for 2 different durations (2 d, n = 36; or 8 d, n = 38) or no antimicrobial treatment (negative control, n = 36). For quarters enrolled in NG, no significant differences were identified for weekly QSCC between quarters in the treated or negative control groups (5.4 log

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Klebsiella Infections; Klebsiella pneumoniae; Longitudinal Studies; Mammary Glands, Animal; Mastitis, Bovine; Milk

The objective of this negatively controlled randomized clinical trial was to compare clinical outcomes of 5-d intramammary treatment using ceftiofur hydrochloride and no antimicrobial treatment of nonsevere culture-negative cases of clinical mastitis (CM). A total of 121 cases of nonsevere (abnormal milk or abnormal milk and udder) culture-negative CM were randomly assigned to either treatment (n = 62) or negative control (n = 59) groups. Quarters assigned to treatment received 1 daily intramammary infusion with an approved commercially available product containing ceftiofur hydrochloride for 5 d. Quarters assigned to the negative control group did not receive any interventions. Enrolled cows were followed for 90 d or until the end of lactation. At enrollment, milk samples from the affected quarter were used for on-farm culture, somatic cell count (SCC) analysis, and further microbiological analysis. During the follow-up period, milk samples were collected for microbiological analysis and SCC analysis. No significant differences between treatment and negative control groups were identified for treatment failure (5% for treatment vs. 10% for negative control, n = 121), quarter-level CM recurrence (8 vs. 5%, n = 91), intramammary infection at 14 or 28 d after enrollment (13 vs. 26%, n = 86), days until clinical cure (4.2 vs. 4.0 d), days to culling (48.3 vs. 36.8 d), daily milk production (43.3 vs. 43.6 kg/cow per day), or weekly quarter SCC (5.5 vs. 5.4 log

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Random Allocation

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Dairying; Escherichia coli; Escherichia coli Infections; Farms; Female; Klebsiella Infections; Klebsiella pneumoniae; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Random Allocation

Ceftiofur (CEF) is a third-generation cephalosporin that is the most widely used antimicrobial in the dairy industry. Currently, violative meat residues in cull dairy cattle are commonly associated with CEF. One potential cause for violative residues is altered pharmacokinetics of the drug due to disease, which could increase the time needed for the residue to deplete. The objectives of this study were (a) to determine the absolute bioavailability of CEF crystalline-free acid (CFA) in healthy versus diseased cows; (b) to compare the plasma and interstitial fluid pharmacokinetics and plasma protein binding of CEF between healthy dairy cows and those with disease; and (c) to determine the CEF residue profile in tissues of diseased cows. For this trial, disease was induced through intramammary Escherichia coli infusion. Following disease induction and CEF CFA administration, for plasma concentrations, there was not a significant effect of treatment (p = 0.068), but the treatment-by-time interaction (p = 0.005) was significant. There was a significantly greater concentration of CEF in the plasma of the DIS cows at T2 hr (p = 0.002), T8 hr (p < 0.001), T12 hr (p = 0.001), and T16 hr (p = 0.002). For PK parameters in plasma, the slope of the terminal phase of the concentration versus time curve was significantly lower (p = 0.007), terminal half-life was significantly longer (p = 0.014), and apparent volume of distribution during the elimination phase was significantly higher (p = 0.028) diseased group. There was no difference in plasma protein binding of CEF and interstitial fluid pharmacokinetics. None of the cows had kidney CEF residues above the US tolerance level following observation of the drug's withdrawal period, but one cow with a larger apparent volume of distribution and longer terminal half-life had tissue residues slightly below the tolerance. Whereas these findings do not support the hypothesis that severely ill cows need longer withdrawal times, alterations in the terminal half-life suggest that it is theoretically possible.

Topics: Animals; Biological Availability; Cattle; Cephalosporins; Escherichia coli Infections; Female; Mastitis, Bovine; Tissue Distribution

The use of antimicrobials in food animals and the emergence of antimicrobial resistance are global concerns. Ceftiofur is the only third-generation cephalosporin labeled for veterinary use in the USA, and it is the drug of choice in the majority of dairy farms for the treatment of mastitis. Here, we use next-generation sequencing to describe longitudinal changes that occur in the milk microbiome before, during, and after infection and treatment with ceftiofur. Twelve animals were intramammary challenged with Escherichia coli in one quarter and randomly allocated to receive intramammary treatment with ceftiofur (5d) or untreated controls. Serial samples were collected from -72 to 216 h relative to challenge from the challenged quarter, an ipsilateral quarter assigned to the same treatment group, and from a third quarter that did not undergo intervention.. Infection with E. coli dramatically impacted microbial diversity. Ceftiofur significantly decreased LogCFUs but had no significant effect on the milk microbiome, rate of pathogen clearance, or somatic cell count. At the end of the study, the microbial profile of infected quarters was indistinguishable from pre-challenge samples in both treated and untreated animals. Intramammary infusion with ceftiofur did not alter the healthy milk (i.e., milk devoid of clots or serous appearance and collected from a mammary gland that shows no clinical signs of mastitis) microbiome.. Our results indicate that the mammary gland harbors a resilient microbiome, capable of reestablishing itself after experimental infection with E. coli independent of antimicrobial treatment.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Mammary Glands, Animal; Mastitis, Bovine; Microbiota; Milk

The study objective was to compare the efficacy of 2 commercial dry cow mastitis formulations containing cloxacillin benzathine or ceftiofur hydrochloride. Quarter-level outcomes included prevalence of intramammary infection (IMI) postcalving, risk for cure of preexisting infections, risk for acquiring a new IMI during the dry period, and risk for clinical mastitis between dry off and 100 d in milk (DIM). Cow-level outcomes included the risk for clinical mastitis and the risk for removal from the herd between dry off and 100 DIM, as well as Dairy Herd Improvement Association (DHIA) test-day milk component and production measures between calving and 100 DIM. A total of 799 cows from 4 Wisconsin dairy herds were enrolled at dry off and randomized to 1 of the 2 commercial dry cow therapy (DCT) treatments: cloxacillin benzathine (DC; n=401) or ceftiofur hydrochloride (SM; n=398). Aseptic quarter milk samples were collected for routine bacteriological culture before DCT at dry off and again at 0 to 10 DIM. Data describing clinical mastitis cases and DHIA test-day results were retrieved from on-farm electronic records. The overall crude quarter-level prevalence of IMI at dry off was 34.7% and was not different between treatment groups. Ninety-six percent of infections at dry off were of gram-positive organisms, with coagulase-negative Staphylococcus and Aerococcus spp. isolated most frequently. Mixed logistic regression analysis showed no difference between treatments as to the risk for presence of IMI at 0 to 10 DIM (DC=22.4%, SM=19.9%) or on the risk for acquiring a new IMI between dry off and 0 to 10 DIM (DC=16.6%, SM=14.1%). Noninferiority analysis and mixed logistic regression analysis both showed no treatment difference in risk for a cure between dry off and 0 to 10 DIM (DC=84.8%, SM=85.7%). Cox proportional hazards regression showed no difference between treatments in quarter-level risk for clinical mastitis (DC=1.99%, SM=2.96%), cow-level risk for clinical mastitis (DC=17.0%, SM=15.3%), or on risk for removal from the herd (DC=10.7%, SM=10.3%) between dry off and 100 DIM. Finally, multivariable linear regression with repeated measures showed no overall no difference between treatments in DHIA test-day somatic cell count linear score (DC=2.19, SM=2.22), butterfat test (DC=3.84%, SM=3.86%), protein test (DC=3.02%, SM=3.02%), or 305-d mature-equivalent milk production (DC=11,817 kg, SM=11,932 kg) between calving and 100 DIM. In conclusion, DC was noninferi

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Cloxacillin; Drug Compounding; Female; Mastitis, Bovine; Prevalence; Risk; Wisconsin

The objective of this study was to compare ceftiofur hydrochloride with a positive control protocol for intramammary treatment of nonsevere clinical mastitis in dairy cows. A total of 264 clinical mastitis cases on 11 commercial dairy farms were treated with intramammary infusions, once a day for 4 d using 1 of 2 treatments: (1) ceftiofur hydrochloride 125mg; or (2) control: tetracycline 200mg + neomycin 250mg + bacitracin 28mg + prednisolone 10mg. Streptococcus agalactiae was the most frequently isolated gram-positive pathogen from clinical mastitis, followed by Staphylococcus aureus. Klebsiella spp. and Escherichia coli were the most isolated gram-negative bacteria from clinical mastitis. No significant differences were observed between treatments regarding the overall clinical cure, bacteriological cure, and new infection. No effect of treatment regimen was observed when the bacterial group (gram-positive vs. gram-negative) was evaluated. The overall clinical cure was 0.79 for ceftiofur-treated cows and 0.74 for control-treated cows, whereas the overall bacteriological cure was 0.79 for ceftiofur-treated cows and 0.76 for control-treated cows. Furthermore, the new intramammary infection was 0.10 for cows treated with ceftiofur and 0.11 for cows treated with control. In conclusion, the use of intramammary ceftiofur hydrochloride for treatment of nonsevere clinical mastitis has similar efficacy as a treatment regimen with a combination of antimicrobial agents (tetracycline + neomycin + bacitracin).

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Female; Klebsiella; Mastitis, Bovine; Staphylococcus aureus

OBJECTIVE To determine the concentration of tilmicosin in mammary gland secretions of dairy cows following administration of an experimental preparation once or twice during the dry period (45-day period immediately prior to calving during which cows are not milked) and to evaluate its efficacy for the treatment of cows with intramammary infections (IMIs) caused by Staphylococcus aureus at dry off (cessation of milking; first day of dry period), compared with that of an intramammary infusion of ceftiofur. ANIMALS 172 cows. PROCEDURES Milk samples were collected for microbiological culture 5 days before dry off and at calving and 15 and 30 days after calving. Cows with Staphylococcus IMIs were randomly assigned to receive an experimental preparation of tilmicosin (20 mg/kg, SC) once at dry off (n = 58) or at dry off and again 20 days later (56) or receive a long-acting intramammary preparation of ceftiofur (500 mg/mammary gland; 56) at dry off. Mammary gland secretions were collected from 5 cows in the tilmicosin-treated groups every 5 days after dry off until calving for determination of tilmicosin concentration. RESULTS Mean maximum concentration of tilmicosin in mammary gland secretions ranged from 14.4 to 20.9 μg/mL after the first dose and was 17.1 μg/mL after the second dose. The bacteriologic cure rate was 100% for all 3 treatments. Tilmicosin was detectable for 0 and 18 days after calving in the milk of cows treated with 1 and 2 doses of tilmicosin, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Administration of an experimental preparation of tilmicosin (20 mg/kg, SC) once to dairy cows at dry off might be useful for the treatment of S aureus IMIs.

Topics: Animals; Cattle; Cephalosporins; Female; Humans; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Staphylococcal Infections; Staphylococcus aureus; Tylosin

To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.. Prospective controlled clinical trial.. 20 lactating Holstein cows.. Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection.. For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.. Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cephalosporins; Clonixin; Female; Mastitis, Bovine; Milk

Few studies have investigated the efficacy of extended ceftiofur therapy and none have focused on extended therapy for naturally occurring clinical mastitis. The objective of this study was to compare the efficacy of extended intramammary ceftiofur therapy of 8 d duration with a standard 2-day regimen for the treatment of naturally occurring mild to moderate clinical mastitis in lactating dairy cows. Holstein cows from 22 dairy herds (n = 241) were randomly allocated to the 2 treatment groups. For each case of mastitis, 125 mg of ceftiofur hydrochloride was administered intramammary once a day for 2 or 8 d. Clinical cure, 21 d after the last treatment, was 89% (98/110) in each group. Bacteriological cure 21 d after the last treatment for the 2- and 8-day regimens were 32% (15/47) and 61% (25/41), respectively, for all bacteria (P = 0.007), 64% (9/14) and 82% (9/11), respectively, for streptococci (P = 0.50), and 0% (0/20) and 47% (9/19), respectively, for Staphylococcus aureus (P = 0.0004). There were no statistical differences between groups for new intramammary infections. Overall, ceftiofur extended therapy increased cure when compared to a 2-day regimen for the treatment of naturally occurring mild to moderate clinical mastitis in lactating dairy cows.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cattle; Cephalosporins; Drug Administration Schedule; Female; Mastitis, Bovine

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 aforementi

Topics: Animals; Anti-Bacterial Agents; California; Cattle; Cephalosporins; Cephapirin; Dihydrostreptomycin Sulfate; Escherichia coli Infections; Female; Lactation; Mastitis, Bovine; Milk; Minnesota; New York; Penicillin G; Staphylococcal Infections; Streptococcal Infections; Wisconsin

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.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Cattle; Cephalosporins; Cephapirin; Female; Mastitis, Bovine

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.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Cephapirin; Dihydrostreptomycin Sulfate; Female; Lactation; Mastitis, Bovine; Milk; Minnesota; Penicillin G Procaine; Pregnancy; Risk

The objective of this study was to evaluate the efficacy of intramammary treatment with ceftiofur hydrochloride of nonsevere, clinical coliform mastitis. One hundred four cases on 5 farms met the enrollment criteria for the study. Escherichia coli was the most common coliform species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Klebsiella spp. and Enterobacter spp. At enrollment, a milk sample from the affected quarter was taken and used for on-farm culture or submitted to the laboratory. For cows in the treatment group, treatment was initiated with ceftiofur hydrochloride via intramammary infusion at 24-h intervals for 5 d according to label standards. Cows in the control group did not receive treatment. Culture results were available on the day after enrollment and only cows with coliform mastitis continued in the treatment and untreated control groups. Bacteriological cure was defined based on 2 posttreatment milk samples. Molecular typing was used for final definition of bacteriological cure. Treatment of nonsevere clinical gram-negative mastitis with ceftiofur hydrochloride resulted in a significant increase in bacteriological cure compared with nontreated controls in animals infected with E. coli or Klebsiella spp. Treated animals clinically improved significantly more compared with control cows. No significant differences were observed between treated and control animals in milk production or linear score before or after clinical mastitis. Treated animals left the study less frequently compared with control animals.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Klebsiella Infections; Mammary Glands, Animal; Mastitis, Bovine

This study evaluated the efficacy of intramammary infusion of ceftiofur hydrochloride for the treatment of intramammary infections present at the last milking of lactation and for prevention of new intramammary infections during the nonlactating period. Cows were randomly assigned to five treatments (untreated negative control, 125, 250, and 500 mg of ceftiofur, and a positive control group receiving 300 mg cephapirin benzathine). A dose of 125 mg of ceftiofur per mammary quarter was effective for treatment of existing infections present at the time of milk cessation, but only the 500-mg dose of ceftiofur per mammary quarter was effective for both treatment of existing intramammary infections at the time of milk cessation and for prevention of new intramammary infections during the nonlactating period.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Administration Schedule; Female; Injections; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Treatment Outcome

The objective of this study was to evaluate the effect of intramuscular (i.m.) ceftiofur (2.2 mg/kg) on important outcomes of systemically mild clinical mastitis episodes in lactating dairy cattle. Cows with clinical mastitis were randomly assigned to a treatment group: pirlimycin intramammary (i.m.m.) (n = 35), pirlimycin i.m.m. and ceftiofur i.m.m. (n = 36), cephapirin i.m.m. (n = 40), cephapirin i.m. and ceftiofur i.m. (n = 33). Sixty-nine, 22, and 9% of initial cultures were gram-negative, gram-positive, and mixed, respectively. Logistic regression analysis showed no significant associations between treatment groups and loss of quarter, recurrence, or culling. Mixed infections, positive milk culture at 7 d after leaving hospital pen, decreased rumen motility, and absence of udder firmness were associated with increased odds of mastitis recurrence. The results suggest that i.m. ceftiofur treatment has no beneficial effects on the outcome of systemically mild clinical mastitis.

Topics: Animals; Cattle; Cephalosporins; Cephapirin; Clindamycin; Female; Injections, Intramuscular; Lactation; Logistic Models; Mammary Glands, Animal; Mastitis, Bovine; Recurrence

Little research has focused on treatment of cows with subclinical mastitis during lactation. Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use that inhibits bacterial cell wall synthesis by interfering with enzymes essential for peptidoglycan synthesis. Ceftiofur should be effective against a wide range of contagious and environmental mastitis pathogens. Objectives of the present study were to evaluate the efficacy of ceftiofur for treatment of subclinical mastitis in lactating dairy cows, and to determine if extended therapy regimens enhanced efficacy of ceftiofur. Holstein and Jersey dairy cows (n = 88) from 3 dairy research herds were used. Cows were enrolled in the study based on milk somatic cell counts >400,000/mL and isolation of the same mastitis pathogen in 2 samples obtained 1 wk apart. Cows with one or more intramammary infections (IMI) were blocked by parity and DIM and allocated randomly to 1 of 3 different ceftiofur treatment regimens: 2-d (n = 49 IMI), 5-d (n = 41 IMI), and 8-d (n = 38 IMI) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. Eighteen cows with 38 IMI were included as an untreated negative control group. A bacteriological cure was defined as a treated infected mammary quarter that was bacteriologically negative for the presence of previously identified bacteria at 14 and 28 d after the last treatment. Efficacy of ceftiofur therapy against all subclinical IMI was 38.8, 53.7, and 65.8% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Four of 38 (10.5%) IMI in control cows were cured spontaneously without treatment. All 3 ceftiofur treatment regimens were significantly better than the negative control, and the 8-d extended ceftiofur treatment regimen treatment group was significantly better than the standard 2-d treatment group. Pathogen groups had significantly different cure rates from one another. The cure rate for the 8-d extended ceftiofur treatment regimen was 70% for Corynebacterium bovis, 86% for coagulase-negative Staphylococcus species, 36% for Staph. aureus, 80% for Streptococcus dysgalactiae ssp. dysgalactiae, and 67% for Strep. uberis.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Corynebacterium Infections; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Staphylococcal Infections; Streptococcal Infections

The objectives of this study were to determine the efficacy of intramuscular administration of ceftiofur to reduce the incidence of case-related death and culling following severe clinical mastitis in lactating dairy cattle. A total of 104 cows with severe clinical mastitis (systemic signs) were enrolled in the study and randomly assigned to one of two treatment groups. Immediately after detection of the case, one group was administered 2.2 mg/kg of ceftiofur intramuscularly, and the dose repeated at 24-h intervals for a total of five doses. The second group of cows did not receive systemic antibacterial therapy. Additionally, all cows in both treatment groups received intramammary pirlimycin (Pirsue) in the affected quarter every 24 h for a total of up to three doses. Also at the onset of the case, all cows on the trial were administered a supportive therapeutic regimen of fluids and anti-inflammatory agents that varied from farm to farm, but was standard within each herd at the discretion of the herd manager and veterinarian. Of all cases 14/104 (13.5%) resulted in a lost cow (died or culled). The proportion of cases that resulted in a lost cow and were treated with ceftiofur (4/51; 7.8%) did not statistically differ from cows that were not treated with ceftiofur (10/53; 18.9%). However, the proportion of cases that resulted in lost cows was higher for those cases that yielded a coliform organism on culture (14/56; 25.0%) than cases that did not yield coliforms (0/48; 0.0%; P < 0.001). Thus, among coliform cases, cows that were not treated with ceftiofur were more likely to be culled or die (10/27, 37.0%; P < 0.05) than cows treated with ceftiofur (4/29, 13.8%). We conclude that intramuscular administration of ceftiofur did not affect the outcome of severe clinical mastitis when all etiologic agents are included in the analysis. However, for severe clinical mastitis cases caused by coliform organisms, ceftiofur therapy reduced the proportion of cases that resulted in cow death or culling. This benefit may be realized because of the amelioration of bacteremic-related pathogenesis.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Clindamycin; Escherichia coli; Escherichia coli Infections; Female; Injections, Intramuscular; Klebsiella; Klebsiella Infections; Mastitis, Bovine; Milk

To determine the efficacy of intramuscular administration of ceftiofur sodium as treatment for intramammary infections attributable to Streptococcus agalactiae, compared with that for a standard treatment of intramammary infusion of penicillin/novobiocin.. Prospective, randomized, controlled trial.. 72 lactating Holstein cows with intramammary infections caused by S agalactiae from 5 commercial dairies in Michigan.. In 36 of 72 infected cows, ceftiofur was administered (2.2 mg/kg of body weight, IM, q 24 h) for 5 days; 150 mg of novobiocin and 100,000 U of procaine penicillin G was infused daily into each mammary gland of the other 36 cows for 2 days. Milk samples were collected aseptically at approximately 4 and 8 weeks after initial treatment. If cows were determined to be infected at 4 weeks after initial treatment, the treatment was repeated.. The cure rate at 4 weeks (91.7%) and at 8 weeks (96.8%) after initial treatment for the penicillin/novobiocin-treated cows was significantly (P < 0.0001) higher, compared with that of the ceftiofur-treated cows (2.8 and 9.1%, respectively). Somatic cell counts were significantly (P < 0.0001) lower in the penicillin/novobiocin-treated group after treatment.. Intramuscular administration of ceftiofur is not efficacious as a treatment to eliminate intramammary infections caused by S agalactiae and should not be used to reduce the prevalence of this organism in dairy herds.

Topics: Animals; Cattle; Cell Count; Cephalosporins; Drug Therapy, Combination; Female; Infusions, Parenteral; Injections, Intramuscular; Logistic Models; Mammary Glands, Animal; Mastitis, Bovine; Milk; Novobiocin; Penicillin G Procaine; Penicillins; Streptococcal Infections; Streptococcus agalactiae; Treatment Outcome

The objective of this study was to describe diversity of Klebsiella pneumoniae isolated from milk collected at detection of nonsevere (abnormal milk or abnormal udder) clinical mastitis (CM) and during a follow-up period. Cases were detected in cows enrolled in a randomized clinical trial (n = 168) conducted using 2 related Wisconsin dairy farms. Cases were randomly assigned to receive 2 d (n = 18) or 8 d (n = 18) of intramammary infusions with an approved product containing ceftiofur hydrochloride or assigned to a negative control group (n = 17). Milk samples were collected from affected quarters at detection and during a 28-d follow-up period. Sufficient DNA was recovered from 53 of 54 Kleb. pneumoniae cultured from quarter milk samples collected at detection of the incident case. Additional Kleb. pneumoniae were recovered from milk samples collected from the same quarters at 14, 21, and 28 d after case detection (n = 35), at detection of recurrent cases in the same quarter (n = 14), and from new cases of CM (n = 3) occurring in enrolled quarters. All Kleb. pneumoniae were used for molecular typing by pulsed-field gel electrophoresis and 90% similarity was used to define homology. Of Kleb. pneumoniae recovered from incident cases, unique strains (n = 41) were identified in milk samples collected from cows on farm A (n = 19) and farm B (n = 22), whereas 12 clonal strains were identified with 8 found only in milk collected from farm A and 4 found in milk samples collected from cows on both farms. Heterogeneous strains of Kleb. pneumoniae genotypes were isolated from incident cases of CM. However, when intramammary infection persisted or when recurrence of CM occurred, clonal strains were isolated at 14, 21, or 28 d. Similar strains of Kleb. pneumoniae genotypes caused persistent CM. In conclusion, initial cases of CM were caused by a wide genetic diversity of Kleb. pneumoniae, but when IMI persisted, the same strain often persisted within the mammary gland up to 28 d.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Electrophoresis, Gel, Pulsed-Field; Farms; Female; Klebsiella Infections; Klebsiella pneumoniae; Mastitis, Bovine; Milk; Molecular Epidemiology; Wisconsin

Mastitis affects cows in all regions of the world and Escherichia coli (E. coli) is by far the most common reason of mastitis. Now antibiotic therapy is still the preferred approach of treating mastitis. However, antibiotic usage is easy to lead to antibiotic resistance. There is an urgent need for developing efficacious alternative antimicrobials. Pheromonicin-NM (PMC-NM) is a new engineered bactericidal peptide consisting of colicin Ia and an anti-porin A antibody mimetic. It can lead to the dissipation of cellular energy and therefore kill the bacteria rapidly. The aim of the present study was to investigate the comparative effects of PMC-NM and antibiotic ceftiofur on antibacterial and innate immune responses of bovine mammary epithelial cells (BMEC) to E. coli infection. We found that E. coli growth was inhibited by PMC-NM from 0.5 h after treatment and was completely inhibited at 3 h, indicating a rapid antibacterial activity for PMC-NM. The mRNA expression of TLR2, IL-1β, IL-8, lactoferrin, LAP, TAP and DEFB1 was increased by PMC-NM treatment at 2 h after E. coli infection, suggesting the enhanced inflammatory responses induced by PMC-NM contribute to pathogens clearance at early phase. By contrast, in E. coli-infected BMECs, ceftiofur treatment upregulated TLR2 and NOD2 levels at 12 h, and extremely elevated transcription levels of TNF-α, IL-1β, IL-8, lactoferrin, LAP, TAP, BNBD5, DEFB1 at 6 h. The excessive expression of these genes at later phase can induce uncontrolled inflammatory responses and finally cause damage. Taken together, PMC-NM might be used as an ideal antibacterial agent against E. coli mastitis.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cells, Cultured; Cephalosporins; Cytokines; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Female; Immunologic Factors; Mammary Glands, Animal; Mastitis, Bovine; Mucin-1

Ceftiofur (CEF) and flunixin meglumine (FLU) are two drugs approved for use in beef and dairy cattle that are frequently used in combination for many diseases. These two drugs are the most commonly used drugs in dairy cattle in their respective drug classes. Two research groups have recently published manuscripts demonstrating altered pharmacokinetics of FLU and CEF in cows affected with naturally occurring mastitis. The objective of this study was to determine whether pharmacokinetics of flunixin meglumine administered intravenously or intramuscularly administered ceftiofur hydrochloride would be altered when co-administered versus individual administration to healthy dairy cattle. Ten cows were utilized in a three-period, three-treatment crossover design, with all cows receiving each treatment one time with a 10-day washout period between treatments. Following treatment, plasma and interstitial fluid samples were collected and stored for later analysis. Additionally, plasma ultrafiltrate was collected using microcentrifugation to determine plasma protein binding of each drug. Drug concentrations in plasma, plasma ultrafiltrate, and interstitial fluid were determined using high-pressure liquid chromatography coupled with mass spectrometry. The results of this trial indicate that drug interactions between FLU and CEF do not occur when the two drugs are administered simultaneously in healthy cattle. Further work is needed to determine whether this relationship is maintained in the presence of severe disease.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Clonixin; Extracellular Fluid; Female; Injections, Intramuscular; Injections, Intravenous; Mastitis, Bovine

Preventive infusion of antibiotics in the mammary gland of cows consumes 11 tons/year of medically relevant antimicrobials, yet, this practice might not be critical to prevent new infections in the healthy mammary gland of cows. Here, we used next-generation sequencing and quantitative real-time PCR to determine the impact of dry cow therapy without antibiotics on milk microbiome and bacterial load, respectively. Cows diagnosed as negative for mastitis at dry off were randomly allocated to receive antibiotic (intramammary ceftiofur hydrochloride) and teat sealant or just teat sealant. Firmicutes was the most abundant phylum, and Corynebacterium, Acinetobacter, and Staphylococcus, often involved in mastitis cases, were the most abundant genera across treatments and time. However, there were no effects of antimicrobial on milk microbiome and bacterial load. Bacterial load was greater at seven days postpartum than at dry off. Dry cow therapy based on teat sealant without antibiotics can be used with no detrimental impacts on milk microbiome and bacterial load in cows with a healthy mammary gland.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Cattle; Cephalosporins; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Microbiota; Milk; Postpartum Period

Ceftiofur hydrochloride (CEF) is occasionally used for the intramammary (IMM) treatment of mastitis. This extralabel manner could result in a drug-residue violation of the milk. The objective of this study was to determine the elimination kinetics of IMM CEF in lactating dairy cattle. The pharmacokinetic profile of CEF after repeated IMM administration in nine healthy cows and nine Staphylococcus aureus infected cows was investigated, alongside determining the MICs of Staph. aureus field strains. The MIC 90 value for CEF in Staph. aureus field strains (n = 31) was 0.25 μg/mL. The t >MIC CEF values for low- production quarters were longer than those for high- and mid- production quarters. The results showed that ceftiofur was detected in milk up to 108 h after the last infusion in both healthy and infected cows. Cows with low milk production eliminate IMM drugs more slowly than cows with higher production. Our findings suggest that this extralabel use is not encouraged and a prudent use is recommended for mastitis therapy. The use of CEF should be reserved for infections where susceptibility tests indicate its efficacy and when alternatives are not available.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cattle; Cephalosporins; Female; Mammary Glands, Animal; Mastitis, Bovine; Microbial Sensitivity Tests; Milk; Staphylococcal Infections; Staphylococcus aureus

Mastitis is a frequent problem among dairy cows, reducing milk yield and increasing cull rates. Systemic therapy with the cephalosporin antimicrobial ceftiofur hydrochloride (CEF) may improve therapeutic outcomes, but the incidence of CEF violative residues has increased annually since 2011. One potential explanation is that disease status may alter the pharmacokinetics (PK) of CEF. To test this hypothesis, we compared the plasma PK of CEF in healthy cows with those with severe endotoxic mastitis. Eight cows with naturally occurring mastitis and 8 clinically healthy cows were treated with 2.2 mg of CEF per kilogram of body weight once daily for 5d via the intramuscular route. Blood was collected at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 8, 16, and 24h after the first CEF administration and every 8h thereafter until 120 h after the final dose. Plasma samples were analyzed for CEF concentrations using liquid chromatography coupled with mass spectrometry. With the exception of time 0, CEF was detected at all time points. The disease group had a significantly higher plasma CEF concentration at t=3h after the first injection and a significantly lower plasma concentration from 40 to 152 h following the first injection, with the exception of the t=64 h time point. Data following the first injection (time 0-24 h) were fit to a single-dose, noncompartmental PK model. This model indicated that the disease group had a shorter plasma half-life. A multidose, noncompartmental model was used to determine steady-state PK. Compared with control cows, the disease group had an initially higher peak concentration and a higher volume of distribution and drug clearance rates. The disease group also had a lower area under the curve per dosing interval, steady-state concentration maximum, and dose-adjusted peak steady-state concentration. All other PK parameters were not different between the 2 groups. Altered PK, as suggested by this trial, may contribute to an increased risk for the development of a violative residue in meat. Further research is needed to more completely characterize drug distribution in diseased cattle and to study the effect of coadministration of other drugs on drug distribution.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Female; Injections, Intramuscular; Mastitis, Bovine; Milk

Antimicrobial usage in food animals has a direct impact on human health, and approximately 80% of the antibiotics prescribed in the dairy industry are used to treat bovine mastitis. Here we provide a longitudinal description of the changes in the microbiome of milk that are associated with mastitis and antimicrobial therapy. Next-generation sequencing, 16 S rRNA gene quantitative real-time PCR, and aerobic culturing were applied to assess the effect of disease and antibiotic therapy on the milk microbiome. Cows diagnosed with clinical mastitis associated with Gram-negative pathogens or negative aerobic culture were randomly allocated into 5 days of Ceftiofur intramammary treatment or remained as untreated controls. Serial milk samples were collected from the affected quarter and the ipsilateral healthy quarter of the same animal. Milk from the mastitic quarter had a higher bacterial load and reduced microbial diversity compared to healthy milk. Resolution of the disease was accompanied by increases in diversity indexes and a decrease in pathogen relative abundance. Escherichia coli-associated mastitic milk samples had a remarkably distinct bacterial profile, dominated by Enterobacteriaceae, when compared to healthy milk. However, no differences were observed in culture-negative mastitis samples when compared to healthy milk. Antimicrobial treatment had no significant effect on clinical cure, bacteriological cure, pathogen clearance rate or bacterial load.

Topics: Animals; Bacteria; Cattle; Cephalosporins; Female; Mastitis, Bovine; Metagenomics; Microbiota; Milk; RNA, Ribosomal, 16S

Development and use of on-farm assays to detect antimicrobial residues in milk is important to reduce the risk of violative residues in marketed milk. The objective of this study was to evaluate the effectiveness of a lateral-flow immunodiagnostic assay (BetaStar Plus, Neogen Corp., Lansing, MI) in detecting ceftiofur residues in milk from individual cows treated for mastitis. This assay is currently approved by the US Federal Drug Administration (FDA) for detecting β-lactam residues in commingled milk. Forty-five dairy cows with clinical mastitis from 4 dairy farms were enrolled and treated intramammary with 125 mg of ceftiofur hydrochloride (Spectramast LC, Zoetis, Madison, NJ) according to the manufacturer's label recommendation. Composite milk samples were collected (A) before first intramammary antimicrobial treatment, (B) before the last intramammary antimicrobial treatment, (C) the last milking of the product-labeled milk withhold, (D) the first milking after the product-labeled milk withhold had been met, and (E) 72 h after the product-labeled milk withhold had been met. Samples were tested using the BetaStar Plus assay within 48 h of collection. Parallel samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and for somatic cell count and milk components. The BetaStar Plus assay identified 6.7, 60.0, 46.7, 22.2, and 6.7% positive samples at each of the respective time points. The assay had sensitivity and specificity of 100 and 84.7%, respectively, compared with liquid chromatography-tandem mass spectrometry analysis using FDA published residue tolerance levels for ceftiofur (or ceftiofur metabolites) as a threshold. The BetaStar Plus assay could be useful for detecting ceftiofur residues in milk from individual cows following intramammary treatment for mastitis before the milk is shipped for processing.

Topics: Animals; Anti-Bacterial Agents; Biological Assay; Cattle; Cell Count; Cephalosporins; Chromatography, Liquid; Drug Residues; Female; Mastitis, Bovine; Milk; Tandem Mass Spectrometry

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.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Cephapirin; Clindamycin; Escherichia coli; Female; Klebsiella; Logistic Models; Mammary Glands, Animal; Mastitis, Bovine; Oxytetracycline; Pasteurella; Penicillins; Staphylococcus; Streptococcus; Wisconsin

Antimicrobials are often used for treatment of bovine mastitis and the possibility of selection for resistant bacteria must be considered. The objectives of this study were to determine the minimum inhibitory concentration of Staphylococcus aureus recovered from cases of clinical and subclinical bovine mastitis, and to determine the prevalence of multidrug resistance in this population. Milk samples were collected from cows on commercial dairy herds (n=13), including quarters (n=1,574) of cows with subclinical mastitis cases, and cows experiencing clinical mastitis cases (n=608). Selected Staph. aureus isolates, obtained from clinical (n=58) and subclinical (n=58) mastitis cases, were used to determine minimum inhibitory concentrations of 12 selected antimicrobials. Of Staph. aureus isolates tested, 87 (75%) did not exhibit resistance to any antimicrobial, 28 (24.1%) exhibited resistance to 1 (n=21) or 2 (n=7) classes of antimicrobials, and 1 (0.9%) exhibited multidrug resistance. All Staph. aureus (clinical and subclinical cases) were inhibited by the range of concentrations tested for ceftiofur and oxacillin. Moreover, no isolates obtained from clinical mastitis cases exhibited resistance to cephalothin, penicillin-novobiocin, or sulfadimethoxine. Of isolates, 3 exhibited resistance to enrofloxacin. Of isolates exhibiting resistance to more than 1 antimicrobial, independent of antimicrobial class, the combination of erythromycin and tetracycline, and ampicillin and penicillin accounted for the majority of resistance. Of isolates tested, 19% were resistant to tetracycline and 14% were resistant to penicillin. Survival curves of Staph. aureus relative to minimum inhibitory concentration demonstrated heterogeneity among case types for ceftiofur, cephalothin, and erythromycin. Multidrug resistance was identified in only 1 isolate obtained from a single farm.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Resistance, Bacterial; Enrofloxacin; Female; Fluoroquinolones; Mastitis, Bovine; Microbial Sensitivity Tests; Milk; Oxacillin; Staphylococcal Infections; Staphylococcus aureus

The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur hydrochloride had lower odds of having clinical and subclinical mastitis in the subsequent early lactation compared with cows treated with penicillin dihydrostreptomycin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Dihydrostreptomycin Sulfate; Drug Combinations; Female; Lactation; Mastitis, Bovine; Milk; Penicillins; Peripartum Period; Pregnancy; Risk Factors

The objectives of this study were to characterize 60-d outcomes after treatment of mild (abnormal milk) and moderate (abnormal milk and abnormal udder) cases of clinical mastitis (CM) occurring in a single quarter of cows on Wisconsin farms (n=4) and to determine risk factors associated with those outcomes. Duplicate milk samples were collected from the affected quarter of each cow for microbiological analysis at the onset of CM (PRE) and 21 d later (POST). Cows were treated only in the affected quarter using an intramammary product containing 125 mg of ceftiofur. Bacteriological cure was defined as absence of pathogens in the POST sample obtained from the enrolled quarter. Recurrence was defined for the cow when CM occurred after the milk-withholding period for the enrolled case of CM. Retention in the herd was defined when a cow was retained within the herd for the 60-d follow-up period. Somatic cell count reduction (SCCR) was defined at the cow level as somatic cell count (SCC) below 200,000 cells/mL at the Dairy Herd Improvement Association test day occurring between 21 to 55 d post-treatment. The effects of farm, days in milk, parity, severity, microbiological diagnosis at PRE, previous milk yield, previous SCC, previous occurrence of CM and treatment duration on selected post-treatment outcomes were assessed using Chi-squared analysis and logistic regression. Microbiological results at PRE were distributed as: Escherichia coli (n=14), Klebsiella spp. (n=11), Enterobacter spp. (n=8), Serratia spp. (n=7), other gram-negative species (n=3), Streptococcus spp. (n=25), coagulase-negative staphylococci (n=4); Staphylococcus aureus (n=1); Streptococcus agalactiae (n=1), other gram-positive species (n=9), and culture negative (n=60). Treated quarters were more likely to experience bacteriological cure when the cow experienced CM for the first time in the lactation and when no pathogen was recovered from PRE milk samples obtained from the enrolled quarter. Parity and bacteriological cure were associated with the probability of recurrence. Greater milk yield at previous Dairy Herd Improvement test was the most important predictor for retention within the herd. When SCC before CM was >200,000 cells/mL the probability of having SCCR after treatment was decreased. When the case experienced bacteriological cure, the cow was less likely to experience recurrent cases and was more likely to have SCCR below 200,000 cells/mL. Post-treatment outcomes, such as recurrenc

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Female; Mammary Glands, Animal; Mastitis, Bovine; Milk; Recurrence; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Wisconsin

The aims of this study were to describe antibiotic use and biosecurity practices among Washington State dairy producers and to evaluate the effectiveness of a collaborative approach to promoting judicious antibiotic use on dairy farms. In collaboration with a statewide industry group, Washington State dairy producers participated in a written, self-administered survey in 2003. They were then provided several educational interventions followed by a second written survey in 2005. Sixty-five percent (381) of dairy producers completed the 2003 survey. The most commonly cited drugs used for disease treatment were penicillin, ceftiofur, and oxytetracycline. Participants also indicated significant preventive uses with 28% using medicated milk replacer. Most producers appeared to consider intramammary infusion at dry-off to be a treatment rather than a preventative practice. Twenty-three percent of initial respondents indicated at least one extra-label use of antibiotics, yet only half routinely consulted with a veterinarian when doing so. Most agreed that using written protocols for disease treatment could reduce errors, but less than one-third had protocols. After the educational intervention there was a tendency toward reduced use of antibiotic medicated milk replacer: 51% of producers who originally reported using medicated milk replacer discontinued this practice, whereas 12% of producers began using medicated milk replacer between the 2003 and 2005 surveys. Most reported that the resources and educational materials were useful. Areas where additional work is needed include reducing the use of medicated milk replacer, increasing veterinary involvement in antibiotic use decisions, implementing treatment protocols, enhancing biosecurity, and ensuring optimal cow and calf immunity.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Colostrum; Dairying; Drug Resistance, Microbial; Female; Health Education; Health Knowledge, Attitudes, Practice; Mastitis, Bovine; Milk Substitutes; Oxytetracycline; Penicillins; Surveys and Questionnaires; Washington

To determine the elimination kinetics of ceftiofur hydrochloride in milk after intramammary administration in lactating dairy cows.. Prospective study.. 5 lactating dairy cows.. After collection of baseline milk samples, 300 mg (6 mL) of ceftiofur was infused into the left front and right rear mammary gland quarters of each cow. Approximately 12 hours later, an additional 300 mg of ceftiofur was administered into the same mammary gland quarters after milking. Milk samples were collected from each mammary gland quarter every 12 hours for 10 days. Concentrations of ceftiofur and its metabolites in each milk sample were determined to assess the rate of ceftiofur elimination.. Although there were considerable variations among mammary gland quarters and individual cows, ceftiofur concentrations in milk from all treated mammary gland quarters were less than the tolerance (0.1 microg/mL) set by the FDA by 168 hours (7 days) after the last intramammary administration of ceftiofur. No drug concentrations were detected in milk samples beyond this period. Ceftiofur was not detected in any milk samples from nontreated mammary gland quarters throughout the study.. Ceftiofur administered by the intramammary route as an extra-label treatment for mastitis in dairy cows reaches concentrations in milk greater than the tolerance set by the FDA. Results indicated that milk from treated mammary gland quarters should be discarded for a minimum of 7 days after intramammary administration of ceftiofur. Elimination of ceftiofur may be correlated with milk production, and cows producing smaller volumes of milk may have prolonged withdrawal times.

Topics: Animals; Anti-Infective Agents, Local; Cattle; Cephalosporins; Chromatography, High Pressure Liquid; Drug Residues; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Prospective Studies; Reagent Kits, Diagnostic

Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, the period around calving, and during early lactation. Strategies for controlling Strep. uberis mastitis are poorly defined and are currently inadequate. Objectives of the present study were to evaluate efficacy of ceftiofur, a new broad-spectrum cephalosporin antibiotic, for treatment of experimentally induced Strep. uberis intramammary infections (IMI) in lactating dairy cows during early lactation and to determine whether extended therapy regimens enhanced efficacy of ceftiofur. Efficacy of extended ceftiofur intramammary therapy regimens was investigated in 37 mammary quarters of 23 dairy cows that developed clinical mastitis following experimental infection with Strep. uberis during early lactation. Cows that developed clinical mastitis during the challenge period were allocated randomly to 3 groups representing 3 different ceftiofur treatment regimens: 2-d (n = 7 mammary quarters), 5-d (n = 16 mammary quarters), and 8-d (n = 14 mammary quarters) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. A bacteriological cure was defined as an experimentally infected quarter that was treated and was bacteriologically negative for the presence of Strep. uberis at 7, 14, 21, and 28 d posttreatment. Percentage of Strep. uberis IMI eliminated was 43, 88, and 100% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Both the 5- and 8-d ceftiofur extended therapy treatment regimens had significantly higher bacterial cure rates than the standard 2-d ceftiofur treatment regimen. The bacterial cure rate of the 8-d ceftiofur extended therapy group was marginally better (P = 0.052) than the 5-d ceftiofur extended therapy group. Results of this study indicate that ceftiofur therapy was effective for eliminating Strep. uberis experimental IMI, and 5- and 8-d extended ceftiofur therapy regimens were more effective than the standard 2-d treatment.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Female; Lactation; Mastitis, Bovine; Milk; Streptococcal Infections

Two antibiotic preparations, tilmicosin and ceftiofur, were tested intramammarily and parenterally against Staphylococcus aureus mastitis in lactating cows. Neither product was effective as a lactating cow treatment at the doses and durations of treatment tested. Injection or infusion of tilmicosin and infusion of ceftiofur resulted in reductions of bacteria present in milk; however, only one quarter treated with infusion of tilmicosin was cured, and no cures were observed for the other treatments. Somatic cell counts were transiently reduced by infusion of ceftiofur and by infusion and injection of tilmicosin; however, they returned to pretreatment values by 28 d posttreatment.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Female; Infusions, Intravenous; Injections, Subcutaneous; Lactation; Macrolides; Mammary Glands, Animal; Mastitis, Bovine; Milk; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Tylosin

The activity of selected antimicrobial agents was determined against strains of Staphylococcus aureus that were isolated from bovine intramammary infections and that were positive or negative for beta-lactamase. A total of 107 S. aureus strains (70 that were positive for beta-lactamase and 37 that were negative for beta-lactamase) were used in the study. Production of beta-lactamase was determined using a chromogenic cephalosporin disk method. Minimum inhibitory concentrations (MIC) for each test strain were determined using a commercially available microdilution panel. The following compounds were tested: penicillin, ampicillin, oxacillin, cephapirin, ceftiofur, penicillin plus novobiocin, erythromycin, and pirlimycin. Of the five beta-lactam compounds tested, penicillin and ampicillin were most affected by beta-lactamase activity, but oxacillin, cephapirin, and ceftiofur were not affected. Penicillin plus novobiocin also demonstrated excellent activity against strains of S. aureus that were both positive and negative for beta-lactamase. Erythromycin and pirlimycin demonstrated good activity against the S. aureus strains that were negative for beta-lactamase; 90% of the isolates had an MIC of < or = 0.5 microgram/ml (MIC90). The MIC90 for erythromycin and pirlimycin for strains that were positive for beta-lactamase was > 64.0 micrograms/ml. However, 8 strains, in addition to producing beta-lactamase, were also resistant to macrolides and lincosaminides. Recalculation of the MIC90 without these 8 strains yielded equivalent values for both erythromycin and pirlimycin with strains that were positive or negative for beta-lactamase (MIC90 < or = 0.5 microgram/ml).

Topics: Ampicillin; Animals; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cattle; Cephalosporins; Cephapirin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Erythromycin; Female; Mammary Glands, Animal; Mastitis, Bovine; Novobiocin; Oxacillin; Penicillins; Staphylococcal Infections; Staphylococcus aureus

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/- SEM peak log10 bacterial concentration in milk of 5.03 +/- 0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 microgram/ml, and was 0.20 microgram/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 microgram/ml and 0.7 +/- 0.1 microgram/ml for infected and noninfected cows, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Temperature; Cattle; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Mammary Glands, Animal; Mastitis, Bovine; Metabolic Clearance Rate; Milk; Reference Values

Twenty-five Staphylococcus aureus strains isolated from bovine mastitis were tested for their susceptibility to ceftiofur. Zone diameter for 30 micrograms disks averaged 39 mm, and minimum inhibitory concentrations ranged from .5 to 1 microgram/ml. Tissue and milk concentrations were determined from biopsy and quarter milk samples collected from eight cows treated with either intramammary infusion of 100 or 200 mg of ceftiofur, one or two intramuscular injections of 500 mg of ceftiofur, or combination therapy of intramammary infusion coupled with intramuscular injection. Three additional cows received two intramammary infusions of 200 mg of cephapirin at 24-h intervals. Intramuscular injections of ceftiofur resulted in tissue and milk concentrations below detectable limits. Staphylococcus aureus was not eliminated from infected mammary glands by infusion of 100 mg of ceftiofur or by injection of 500 mg of ceftiofur by 48 h after treatment. Combination therapy of 100 mg of ceftiofur infused and 500 mg injected reduced S. aureus numbers in milk and tissue markedly, as did infusion of 200 mg of ceftiofur. Cows receiving intramammary infusion of 200 mg of ceftiofur (two doses at 24-h intervals) had highest concentrations in milk (450 micrograms/ml at 4 and 6 h) and in tissue (.08 microgram/mg at 30 h). These concentrations are similar to those obtained with two 200-mg doses of cephapirin at 24-h intervals. Histologic analysis of mammary parenchymal tissues showed that combination therapy resulted in higher percentages of alveolar luminal area and lower percentages of interalveolar stroma compared with infusion or injection alone. Histology of quarters receiving combination therapy was not different from that of quarters receiving cephapirin infusion alone.

Topics: Animals; Cattle; Cephalosporins; Cephapirin; Female; Infusions, Parenteral; Injections, Intramuscular; Mammary Glands, Animal; Mastitis, Bovine; Microbial Sensitivity Tests; Milk; Staphylococcal Infections; Staphylococcus aureus