Efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for the treatment of acute postpartum metritis in dairy cows

OBJECTIVE: To evaluate the efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for treatment of acute postpartum metritis (APM) in dairy cows. DESIGN: Multilocation, randomized block, field trial. ANIMALS: 406 cows in the first 14 days postpartum. PROCEDURE: Cows with rectal temperatures > or = 39.5 degrees C (103.1 degrees F) without clinical signs of respiratory or gastrointestinal tract disease and with a fetid vaginal discharge were allocated randomly in blocks of 3 to 3 treatment groups: sterile saline (0.9% NaCl) solution administered at a dosage of 2 mL/45.4 kg (2 mL/100 lb), SC or IM, once daily for 5 days (control); or ceftiofur hydrochloride administered at a dosage of 1.1 or 2.2 mg of ceftiofur equivalents (CE)/kg (0.5 or 1 mg/lb, respectively), SC or IM, once daily for 5 days. Cows were evaluated on days 6, 10, and 14, and clinical cure or failure to cure was determined. Clinical cure was defined as no additional antimicrobial treatment administered, rectal temperature < 39.5 degrees C, and absence of a fetid vaginal discharge. RESULTS: On day 14, clinical cure rates were 77%, 65%, and 62% for the 2.2 mg of CE/kg, 1.1 mg of CE/kg, and control groups, respectively. No significant differences were detected in clinical cure rates between control and treatment groups on day 10 or 6. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur hydrochloride administered at a dosage of 2.2 mg of CE/kg, SC or IM, once daily for 5 days was efficacious for treatment of APM in dairy cows.     

Dose determination and confirmation for ceftiofur crystalline-free acid administered in the posterior aspect of the ear for control and treatment of bovine respiratory disease

Three studies were conducted to determine and confirm the effective dosage rate of ceftiofur crystalline-free acid sterile suspension (CCFA-SS, 200 mg ceftiofur equivalents [CE]/ml), a long-acting ceftiofur formulation, for control and treatment of bovine respiratory disease (BRD). In each study, CCFA-SS was administered once by subcutaneous (SC) injection in the middle third of the posterior aspect of the ear. Study 1 was conducted using an intratracheal challenge with Mannheimia (formerly Pasteurella) haemolytica and dosages ranging from 0 to 8.8 mg CE/kg to select a dosage for further field testing. In Study 2, a single dose of CCFA-SS at 0.0, 4.4, or 6.6 mg CE/kg was administered when uniform clinical signs of BRD were present in feedlot cattle. Study 3 was conducted in several feedlots to evaluate the efficacy, practicality, and safety of CCFA-SS at 4.4 or 6.6 mg CE/kg compared with a placebo control or tilmicosin for preemptive control of BRD. In Study 1, the effective dose was determined to be 5.35 mg CE/kg; therefore, 4.4 and 6.6 mg CE/kg were selected as the dosages for further field testing. Administration of CCFA-SS at 4.4 or 6.6 mg CE/kg improved treatment success compared with negative controls (P < or =.05 for both doses) in Study 2. In Study 3, a single administration of 4.4 or 6.6 mg CE/kg was comparable to tilmicosin (P <.001) and was significantly better than placebo (P <.001) for the control of BRD. Using the ear as an administration site was acceptable under field conditions and was well tolerated by all animals. These studies demonstrated that a single administration of CCFA-SS by SC injection in the middle third of the posterior aspect of the ear at 4.4 or 6.6 mg CE/kg is effective, safe, and practical for preemptive control and treatment of the bacterial component of BRD in feedlot cattle. Administration in an inedible tissue results in a short withdrawal time and no injection-site trimming at slaughter.     

Efficacy of sustained release needle-less ceftiofur sodium implants in treating calves with bovine respiratory disease

Three experiments were conducted to determine preliminary efficacy of sustained release needle-less implants in effecting cure in calves with bovine respiratory disease. One hundred and twenty beef calves with a rectal temperature > or = 40 degrees C and shallow or labored respiration and coughing were used in these experiments. Four groups (1-ceftiofur sodium injections [days 1, 2, and 3], 2-ceftiofur sodium needle-less implants [days 1, 2, and 3], 3-ceftiofur sodium needle-less implants [days 1 and 3], and 4-ceftiofur sodium needle-less implants [day 1] were included. All treatments contained 250 mg of ceftiofur sodium and were administered intramuscularly in the neck after diagnosis of bovine respiratory disease. Experiment 1 included 20 calves (group 1-10 calves and group 3-10 calves; 213 to 255 kg) and calves were monitored for clinical efficacy. Experiment 2 included five calves per group (all four groups; 164 to 192 kg) and calves were bled frequently after treatment for desfuroylceftiofur (the primary ceftiofur metabolite) concentrations. Experiment 3 included 20 calves per group (all four groups; 160 to 205 kg) and calves were monitored for clinical efficacy. Blood desfuroylceftiofur concentrations remained above the minimum inhibitory concentration for Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus for 24 hours after injection and 72 hours after implantation (P < 0.05). Mortalities and the number of calves with a positive response and relapse response were similar (P < 0.25) among the four groups. In summary, the administration of one-250 mg ceftiofur sodium needle-less sustained release implant was as efficacious in treating bovine respiratory disease as three daily 250 mg injections of ceftiofur sodium.     

Evaluation of antibiotics for treatment of cattle infected with Leptospira borgpetersenii serovar hardjo

OBJECTIVE: To evaluate antibiotics for treatment of cattle with leptospirosis caused by Leptospira borgpetersenii serovar hardjo. DESIGN: Randomized controlled trial. ANIMALS: 42 healthy mixed-breed cattle. PROCEDURE: Cattle were inoculated via conjunctival instillation with L. borgpetersenii serovar hardjo. After infection and urinary shedding of L. borgpetersenii were confirmed, cattle were treated with various antibiotics. To determine effectiveness of antibiotic treatment, urinary shedding of L. borgpetersenii was monitored for 4 to 6 weeks after administration of antibiotics, using darkfield microscopic examination, microbial culture, immunofluorescence testing, and a polymerase chain reaction assay. RESULTS: All inoculated cattle developed leptospirosis and shed leptospires in their urine. The following antibiotic treatments resulted in elimination of urinary shedding of leptospires: a single injection of oxytetracycline (20 mg/kg 19 mg/lb] of body weight, IM), tilmicosin (10 mg/kg [4.5 mg/lb], SC), or a combination product that contained dihydrostreptomycin-penicillin G (25 mg/kg [11.4 mg/lb], IM) or multiple injections of ceftiofur sodium (2.2 or 5 mg/kg [1 or 2.3 mg/lb], IM, once daily for 5 days, or 20 mg/kg, IM, once daily for 3 days). CONCLUSIONS AND CLINICAL RELEVANCE: Successful resolution of leptospirosis in cattle by administration of dihydrostreptomycin-penicillin G confirms results obtained by other investigators. Three other antibiotics (oxytetracycline, tilmicosin, and ceftiofur) also were effective for resolving leptospirosis and may be useful substitutes for dihydrostreptomycin, an antibiotic that is no longer available for use in food-producing animals in the United States. Cost, safety, and withdrawal times of these various treatment options need to be considered.     

Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.     

A field evaluation of the efficacy of tolfenamic acid and oxytetracycline in the treatment of bovine respiratory disease

Deleforge, J., Thomas, E., Davot, J.L., Boisrame, B. A field evaluation of the efficacy of tolfenamic acid and oxytetracycline in the treatment of bovine respiratory disease. J. vet. Pharmacol Therap. 17,43–47.
In ablinded multicentre trial 313 cattle showing clinical signs of respiratory disease were allocated randomly into three groups, treated intramuscularly with a long-acting oxytetracycline formulation at a dose rate of 20 mg/kg bodyweight in combination with vehicle alone (placebo) or with tolfenamic acid at 2mg/kg, bodyweight once or on two occasions with a 48-h interdosing interval. The clinical status of the animals was monitored for 5 days using a specific scoring system and weight gain was calculated between day 0 and day 21. Relapses were monitored from day 5 until day 21. When oxytetracycline was combined with two injections of tolfenamic acid, there was a significant (P < 0.04) improvement in the clinical resolution. This regimen also produced non-significant improvements in cure rate, reduced frequency of relapses and improved weight gain.     

Comparison of enrofloxacin and ceftiofur sodium for the treatment of relapse of undifferentiated fever/bovine respiratory disease in feedlot cattle

This commercial field trial compared the efficacy of enrofloxacin and ceftiofur sodium in beef cattle at high risk of developing undifferentiated fever (UF), also known as bovine respiratory disease (BRD) that received tilmicosin at feedlot arrival, were diagnosed and initially treated for UF with tilmicosin, and subsequently required a second UF treatment (first relapse). Feedlot cattle (n = 463) were randomly assigned to 2 experimental groups: ENRO or CEF. Second UF relapse, 3rd UF relapse, overall case fatality and BRD case fatality rates were lower in the ENRO group than in the CEF group (P < 0.05). There were no differences in average daily gain (allocation to re-implant date), chronicity, histophilosis case fatality or miscellaneous case fatality rates between the groups (P ≥ 0.05). A per-animal economic advantage of Can$57.08 was calculated for the ENRO group versus the CEF group. In feedlot cattle in western Canada at high risk of developing UF, it was more cost effective to administer enrofloxacin than ceftiofur sodium for treatment of UF relapse.     

Efficacy evaluation of the use of oral tilmicosin in pneumonic calves

A trial was carried out on a beef cattle farm to obtain efficacy data for the treatment of naturally occurring bronchopneumonia in calves under commercial production conditions. The treatment was administered by medicating milk with three different tilmicosin doses mixed in the first 80% of the daily milk ration. According to the clinical results, all three treatment regimens proved to be effective. The efficacies of the reduced dose of 12.5 mg tilmicosin/kg body weight daily for 5 days and of the reduced treatment duration with 25 mg/kg b.w. daily for 3 days were equivalent to a previously proven dose of 25 mg/kg b.w. daily for 5 days.     

The effects on the pharmacokinetics of intravenous ceftiofur sodium in dairy cattle of simultaneous intravenous acetyl salicylate (aspirin) or probenecid

Ceftiofur sodium is a third-generation cephalosporin antibiotic. It is possible that non-steroidal anti-inflammatory drugs such as acetyl salicylate (aspirin) may be used concomitantly with ceftiofur sodium in dairy cattle. Therefore this study evaluated potential pharmacokinetic interactions between ceftiofur sodium and aspirin. In addition, this study evaluated the potential for interaction between ceftiofur and its active metabolites and the organic anion transporter. The organic anion transporter substrate used in this evaluation was probenecid. Ten healthy, non-pregnant, non-lactating dairy cows were used in a randomized complete three-way crossover design. In repeated experiments all cows were administered: (1) 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (2) 10 mg of probenecid per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (3) 26 mg of aspirin per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus. For treatment with ceftiofur sodium alone, the mean volume of distribution at steady-state V_d(33) was 0.2 ± 0.06 L/kg, the mean volume of distribution by the area method V_d(area) was 0.38 ± 0.22 L/kg, mean residence time (MRT) was 6.5 ± 1.8 h, mean residence time in peripheral tissues (MRT_p) was 2.6 ± 1.0 h, total body clearance (Cf) was 0.032 ± 0.013 L/kg/h and elimination rate constant (P) was 0.097 ± 0.044 h^-1(mean ± standard deviation). No statistically significant changes were detected as a result of preceding treatment with aspirin. Preceding treatment with probenecid resulted in a decrease in both Cl (0.007 ± 0.005 L/kg/h) and MRT_p (0.89 ± 0.45 h). These results suggest that ceftiofur or its metabolites may interact with the organic anion transporter, but that consideration of alterations to dose and dose interval may not be necessary when ceftiofur sodium is administered to the cow concomitantly with a single dose of aspirin.     

The pharmacokinetics of salicylate in dairy cattle are not altered by simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate (Aspirin)

This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a crossover using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (IV) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin IV. Plasma samples were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected ( P <0.05). Using 90% confidence intervals, and testing for changes of > 20%. control values, elimination half-life ( t ₁/₂), apparent volume of distribution ( V _d), area under the plasma concentration versus time curve ( AUC ) and mean residence time ( MRT ) were not altered. For control animals the elimination rate constant ( k _el) and total body clearance ( Cl ) were 1.35/pm0.43 h⁻¹ and 20.2/pm6.1 ml/h.kg respectively (mean/pmSD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.     

Efficacy of a long-acting formulation of ceftiofur crystalline-free acid for the treatment of naturally occurring infectious bovine keratoconjunctivitis

OBJECTIVE: To evaluate the efficacy of ceftiofur crystalline-free acid (CCFA) administered into the posterior aspect of an ear for treatment of corneal ulceration associated with naturally occurring infectious bovine keratoconjunctivitis (IBK). ANIMALS: 78 beef calves located at Sierra Foothills Field Station (SFS) and 52 calves located at a commercial dairy (CD). All calves were from 3 to 9 months old. PROCEDURE: At each site, calves were randomly allocated to 1 of 2 treatment groups by use of a block design determined by corneal ulcer size. A single dose of CCFA (6.6 mg of ceftiofur equivalents/kg, s.c.) was administered into the posterior aspect of a pinna. A second group of calves received a single dose of vehicle (0.03 mL/kg, s.c.; controls). Corneal ulcers were photographed, and clinical signs were assessed in calves every 3 to 4 days for 21 days. RESULTS: A positive treatment effect was detected at SFS. Results at the CD were inconclusive because ulcer healing occurred rapidly in control and CCFA-treated calves. At SFS, treatment with CCFA resulted in shorter mean healing times, smaller corneal ulcer surface area measurements, amelioration of ocular discharge and photophobia, and a 50% increase in the percentage of calves healed by day 14. After adjustment for initial corneal ulcer size, treatment with CCFA resulted in a 4-fold increase in the odds of corneal ulcer healing by day 14, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of CCFA administered into the posterior aspect of a pinna had a positive treatment effect against naturally occurring IBK in calves with corneal ulcerations.     

Comparison of the use of regulatory assays and high-performance liquid chromatography for detection of residues of ceftiofur sodium metabolites in tissue specimens of culled dairy cattle

OBJECTIVE: To compare the results of regulatory screening and confirmation assays with those of high-performance liquid chromatography (HPLC) in the detection of ceftiofur metabolites in the tissues of culled dairy cattle. ANIMALS: 17 lactating Holstein dairy cows. PROCEDURE: Daily IM injections of ceftiofur sodium were administered at a dose of 2.2 mg of ceftiofur equivalents/kg (n = 6) or 1.0 mg of ceftiofur equivalents/kg (10) for 5 days. Following withdrawal times of 12 hours (high-dose ceftiofur) and either 5 or 10 days (low-dose ceftiofur), cows were slaughtered and liver, kidney, and diaphragmatic muscle specimens were harvested and analyzed by HPLC and standard regulatory methods that included the following assays: the swab test on premises, the fast antimicrobial screen test, the calf antibiotic and sulfa test, and the 7-plate bioassay confirmation test. RESULTS: In all tissue specimens, residues of ceftiofur and desfuroylceftiofur-related metabolites, as measured by HPLC, were less than regulatory tolerance, as defined by the FDA. False-positive screening assay results were more likely for tissue specimens that had been frozen for shipment to a federal laboratory, compared with fresh tissue specimens that were assayed at the slaughter establishment (23% vs 3% false-positive results, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The observation that fresh tissues had negative results on screening assays, whereas subsets of the same tissue specimens had false-positive results on screening assays following freezing, suggests that freezing and thawing interferes with microbial inhibition-based regulatory screening assays.     

Effects of age on the pharmacokinetics of single dose ceftiofur sodium administered intramuscularly or intravenously to cattle

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughage/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. C_max values were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 μg ceftiofur free acid equivalents/mL for 72 h in 7-day-old calves, but were less than 0.150 μg/mL within 48 h following IV or IM injection for 6- and 9-month-old calves. Intramuscular bioavailability, assessed by comparing the model-derived area under the curve (AUC_mod) from IM and IV injection at each age, appeared to be complete. After IV administration, the AUC_mod in 7-day-old and 1-month-old calves (126.92±21.1 μg-h/mL and 135.0±21.6 μg.h/mL, respectively) was significantly larger than in 3-, 6- and 9-month-old calves (74.0±10.7 μg.h/mL, 61.0±17.7 μg.h/mL and 68.5±12.8 μg.h/mL, respectively; P< 0.0001). The V_d(ss) decreased linearly within the first 3 months of life in cattle (0.345±0.0616 L/kg, 0.335±0.919 L/kg and 0.284±0.0490 L/kg, respectively; P= 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. The Cl_b was significantly smaller in 7-day-old and 1-month-old calves (0.0178±0.00325 L/h.kg and 0.0167±0.00310 L/h.kg, respectively) than in 3-, 6- and 9-month-old calves (0.0303±0.0046 L/h.kg, 0.0398±0.0149 L/h.kg and 0.0330±0.00552 L/h.kg, respectively; P≦0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above the MIC for bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that peak tissue concentrations would be no higher in neonatal calves than in more mature cattle.     

头孢噻呋混悬剂治疗人工复制仔猪黄白痢的效果观察

将头孢噻呋混悬剂以高、中、低(10、52、.5 mg/kg)3个剂量组,分别肌肉注射治疗仔猪黄白痢,每24 h用药1次,连用3次,同时设对照组。结果表明,头孢噻呋混悬剂3个剂量组和头孢噻呋钠注射液对照组对仔猪黄白痢均有明显的治疗效果,成活率可达80%~100%,极显著的高于感染对照组(P<0.01)。头孢噻呋混悬剂中、高剂量组成活率显著高于头孢噻呋混悬剂低剂量组及头孢噻呋钠注射液组(P<0.01)。表明头孢噻呋混悬剂能减少大肠埃希菌人工感染引起的临床症状,降低病死率。作为注射剂治疗仔猪黄白痢,剂量以5 mg/kg~10 mg/kg为佳。     

Feedlot performance of steers treated concurrently with ceftiofur crystalline-free acid subcutaneously in the posterior aspect of the ear and a growth-promoting implant

Ceftiofur crystalline-free acid sterile suspension (CCFA-SS), a long-acting formulation of ceftiofur formulated for subcutaneous injection in the middle third of the posterior aspect of the ear, is being developed for the control and treatment of bovine respiratory disease. A study was designed to evaluate average daily gain (ADG) and feed efficiency (FE) for cattle through 140 days in the feedlot after CCFA-SS was administered concurrently in the same ear with a growth-promoting implant. On Day 0, steers (n = 207) averaging 189 kg in weight were randomly assigned to the following treatments: Revalor -S implant (120 mg trenbolone acetate and 24 mg estradiol per implant; Hoechst-Roussel Agri-Vet Company) (n = 64); CCFA-SS at 6.6 mg ceftiofur equivalents/kg and a Revalor -S implant (n = 64); untreated control (no CCFA-SS or implant) (n = 63); or CCFA-SS only (n = 16). On Day 56, an Implus-S implant (200 mg progesterone USP plus 20 mg estradiol benzoate; Pharmacia and Upjohn Animal Health) was administered to all cattle. Tolerance of administration of all materials was observed visually and by palpation of the treated ears. Average daily gain and FE from Day 0 through Day 56 were significantly (P <.001) better for steers of both groups with an implanted growth-promotant than for untreated controls. From Day 0 through Day 140, ADG was significantly (P <.05) better for cattle given an implant or an implant plus CCFA-SS than for untreated controls and FE was significantly (P <.05) better for cattle given an implant plus CCFA-SS than for controls. Mild or moderate, transient swelling of the treated ear was observed in two cattle (CCFA-SS plus implant) on Day 52. On Day 56, 88 % of cattle treated with CCFA-SS, 84 % of the cattle treated with an implant plus CCFA-SS, and 100 % of cattle in other groups were normal. Administration of CCFA-SS in the middle third of the posterior aspect of the ear at the same time as growth-promoting implants did not affect performance of cattle in the feedlot and was well tolerated by the animals.     

Comparison of three oxytetracycline regimes for the treatment of persistent Anaplasma marginale infections in beef cattle

Anaplasmosis, caused by the tick-borne rickettsia, Anaplasma marginale, is an economically important disease of cattle in the United States and worldwide. Cattle that recover from acute infection become carriers in which low or microscopically undetectable A. marginale rickettsemia persists. Tetracycline antimicrobials are currently the only drug used in the US for treatment of acute anaplasmosis. There are currently no drugs specifically licensed for elimination of persistent infections. This study tested the efficacy of three oxytetracycline treatment regimens to clear A. marginale from cattle that were persistently infected. Forty Angus x Simmental steers, aged 6-12 months were experimentally infected with A. marginale. After the steers recovered from acute infection, seroconverted, and were confirmed infected using nested PCR followed by DNA hybridization, the carrier status of each animal was ascertained by sub-inoculation of blood into a separate, splenectomized Holstein calf. The steers were then blocked by bodyweight and randomly assigned as follows to four treatment groups: Treatment A, 300 mg/ml solution of oxytetracycline (Tetradure LA-300, Merial Canada Inc.) administered at 30 mg/kg, by intramuscular (i.m.) injection on day 0; Treatment B, the same 300 mg/ml solution of oxytetracycline administered at 30 mg/kg, i.m. on day 0 and again on day 5; Treatment C, a 200 mg/ml solution of oxytetracycline (Liquamycin LA-200, Pfizer Animal Health) administered at 22 mg/kg, intravenously (i.v.), q 24 h for 5 days (a treatment dose that corresponds with current Office International des Epizooties (OIE) recommendations for treatment prior to export). The fourth group consisted of untreated infected control cattle. All steers were still nested PCR and cELISA positive at 60 days after treatment. Infection was confirmed by subinoculation of blood into a splenectomized Holstein calf. These results demonstrated that the treatment regimens tested failed to clear A. marginale infections in carrier cattle.     

Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats

Twelve (12) lactating dairy goats (46–71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC _0–∞ was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC _0–∞ was dose-proportional from 1.1–2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by C _max, and serum concentrations were dose-proportional after the multiple dosing regimen.     

Comparison of plasma pharmacokinetics and bioequivalence of ceftiofur sodium in cattle after a single intramuscular or subcutaneous injection

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. This study was designed to compare the bioequivalence of the sodium salt in cattle after a single intramuscular (i.m.) or subcutaneous dose (s.c.) of 2.2 mg ceftiofur equivalents/kg body weight. The criteria used to evaluate bioequivalence were (1) the area under the curve from time of injection to the limit of quantitation (LOQ) of the assay (AUC0-LOQ), and (2) time concentrations remained above 0.2 microg/mL (t>0.2). Twelve crossbred beef cattle were enrolled in a three-period, two-treatment crossover trial, with a minimum 2-week washout period between doses of 2.2 mg ceftiofur equivalents/kg. Blood samples were collected serially for up to 72 h post-injection. Plasma samples were then analyzed using a validated assay that measures ceftiofur, and all desfuroylceftiofur-related metabolites, by high-performance liquid chromatography (HPLC) as the stable derivative, desfuroylceftiofur acetamide. A maximum plasma concentration (Cmax) of 13.9+/-3.55 microg/mL was observed from 0. 67-2.0 h after i.m. administration, whereas a Cmax of 13.6+/-3.85 microg/mL was observed from 0.67-3.0 h after s.c. administration. The AUC0-LOQ was 108+/-35.0 microg. h/mL after i.m. dosing, compared with 105+/-29.8 microg. h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC0-LOQ for the i.m. and s.c. routes of administration was satisfied. The t>0.2 was 49.2+/-8.55 h after i.m. administration, compared with 47.0+/-9.40 h after s.c. administration. The pre-established criterion for equivalence of the t>0.2 for i.m. and s.c. administration was satisfied. The equivalence of AUC0-LOQ and t>0.2 for i.m. and s.c. administration of 2.2 mg ceftiofur equivalents (CE)/kg doses of ceftiofur sodium suggest similar therapeutic efficacy and systemic safety for the two routes of administration.     

Treatment of respiratory infections in horses with ceftiofur sodium.

Ceftiofur sodium was evaluated as a therapy for respiratory infections in horses. This cephalosporin antimicrobial was administered intramuscularly every 24 h and at a dose of 2.2 mg/kg (1.0 mg/lb) of body weight. The efficacy of ceftiofur sodium was compared with that of a positive control drug, ampicillin sodium (recommended dose of 6.6 mg/kg [3 mg/lb], given every 12 h). Both treatments were continued for 48 h after clinical symptoms were no longer evident (maximum of 10 days). Fifty-five (55) horses with naturally acquired respiratory infections were included in the study; 28 were treated with ceftiofur and 27 with ampicillin. Clinical improvement was recorded for 92.9% of the patients treated with ceftiofur and 92.6% of the animals receiving ampicillin. Both therapies reduced body temperatures to an afebrile level after 2 days of treatment. Complete recovery/cure was noted for 78.6% of the ceftiofur patients and 59.3% of the horses treated with ampicillin. Supporting variables (depression/malaise, respiration/dyspnoea, nasal discharge) were assessed and these also substantiated the effectiveness of the treatments. Both antibiotics were well tolerated. Neither pain nor swelling were noted at the ceftiofur injection site(s). None of the animals developed diarrhoea. Data from this study indicated that ceftiofur sodium is an effective and safe treatment for respiratory infections in horses.