ceftiofur and tilmicosin

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

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

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.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Cost-Benefit Analysis; Enrofloxacin; Fluoroquinolones; Male; Recurrence; Respiratory Tract Diseases; Treatment Outcome; Tylosin; Weight Gain

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.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Dose-Response Relationship, Drug; Ear, External; Haemophilus; Injections, Subcutaneous; Macrolides; Mannheimia haemolytica; Pasteurella multocida; Pasteurellosis, Pneumonic; Suspensions; Treatment Outcome; Tylosin

To evaluate antibiotics for treatment of cattle with leptospirosis caused by Leptospira borgpetersenii serovar hardjo.. Randomized controlled trial.. 42 healthy mixed-breed cattle.. 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.. 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).. 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.

Topics: Animals; Anti-Bacterial Agents; Bacteriuria; Cattle; Cattle Diseases; Cephalosporins; Dihydrostreptomycin Sulfate; Drug Therapy, Combination; Female; Fluorescent Antibody Technique; Leptospira; Leptospirosis; Macrolides; Male; Oxytetracycline; Penicillin G; Polymerase Chain Reaction; Treatment Outcome; Tylosin

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. This survey was conducted to determine the association between antimicrobial class selection for treatment and retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. Furthermore, the frequency of resistant BRD bacterial isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug were associated with a higher frequency of resistant BRD pathogen isolation. In particular, first treatment with tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant M. haemolytica among all antimicrobial combinations. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. However, prospective studies are needed to determine the clinical relevance to antimicrobial stewardship programs in livestock production systems.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Drug Resistance, Microbial; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Pasteurellaceae; Prospective Studies; Recurrence; Respiratory Tract Diseases; Serogroup; Tylosin

Actinobacillus pleuropneumoniae, Pasteurella multocida and Streptococcus suis are prevalent bacterial causes of swine infections. Morbidity, mortality and positively impacting the financial burden of infection occurs with appropriate antimicrobial therapy. Increasing antimicrobial resistance complicates drug therapy and resistance prevention is now a necessity to optimize therapy and prolong drug life. Mutant bacterial cells are said to arise spontaneously in bacterial densities of 107-109 or greater colony forming units/ml. Antibiotic drug concentration inhibiting growth of the least susceptible cell in these high density populations has been termed the mutant prevention concentration (MPC). In this study MPC and minimum inhibitory concentration (MIC) values of ceftiofur, enrofloxacin, florfenicol, tilmicosin and tulathromycin were determined against the swine pathogens A. pleuropneumoniae, P.multocida and S. suis. The following MIC90/MPC90 values (mg/L) for 67 A. pleuropneumoniae and 73 P. multocida strains respectively were as follows: A. pleuropneumoniae 0.031/0.5, ≤0.016/0.5, 0.5/2, 4/32, 2/32; P. multocida 0.004/0.25, 0.016/0.125, 0.5/0.5, 8/16, 0.5/1. For 33 S. suis strains, MIC90 values (mg/L) respectively were as follows: 1, 0.25, 4, ≥8 and ≥8. A total of 16 S. suis strains with MIC values of 0.063-0.5 mg/L to ceftiofur and 0.25-0.5 mg/L to enrofloxacin were tested by MPC; MPC values respectively were 0.5 and 1 mg/L respectively. MPC concentrations provide a dosing target which may serve to reduce amplification of bacterial subpopulations with reduced antimicrobial susceptibility. Drug potency based on MIC90 values was ceftiofur > enrofloxacin >florfenicol = tulathromycin > tilmicosin; based on MPC90 values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Actinobacillus pleuropneumoniae; Animal Husbandry; Animals; Anti-Bacterial Agents; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Heterocyclic Compounds; Microbial Sensitivity Tests; Pasteurella multocida; Streptococcus suis; Swine; Swine Diseases; Thiamphenicol; Tylosin

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Disaccharides; Drug Resistance, Multiple, Bacterial; Enrofloxacin; Fluoroquinolones; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Thiamphenicol; Tylosin; United States

The relative effect of metaphylactic ceftiofur crystalline free acid (CCFA) versus metaphylactic tilmicosin was evaluated in beef calves under commercial feedlot conditions in Nebraska. At feedlot arrival, 11,605 animals at ultrahigh risk of developing bovine respiratory disease (BRD) were allocated to one of three experimental groups: CCFA-3 (6.6 mg/kg SC), CCFA-7 (6.6 mg/kg), or TILM-3 (tilmicosin, 10 mg/kg SC). Animals were eligible for subsequent BRD treatment 3 (CCFA-3 and TILM-3 groups) or 7 (CCFA-7 group) days later. Compared with the TILM-3 group, overall chronicity, overall mortality, BRD mortality, and metabolic mortality rates were significantly (P < .05) lower in the CCFA-3 and CCFA-7 groups; average daily gain was significantly (P < .05) higher in the CCFA-3 group; the proportion of quality grade No Roll carcasses was significantly (P < .05) lower in the CCFA-3 and CCFA-7 groups; and there were per-animal advantages of 22.05 dollars and 18.98 dollars in the CCFA-3 and CCFA-7 groups, respectively. In beef calves at ultrahigh risk of developing BRD, it is more cost effective to administer metaphylactic CCFA than tilmicosin at feedlot arrival.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Dose-Response Relationship, Drug; Injections, Subcutaneous; Macrolides; Male; Random Allocation; Risk Factors; Treatment Outcome; Tylosin

To correlate serum concentrations of fibrinogen (Fib), haptoglobin (Hap), serum amyloid-A (SAA), and alpha-1 acid glycoprotein (AGP) with clinical respiratory tract disease and response to treatment in transport-stressed feedlot cattle fed vitamin E-supplemented diets.. 387 heifer calves (mean initial weight, 197 kg).. Calves purchased from an order buyer were delivered to a feedlot to study the effects of dietary supplementation with 2,000 IU of vitamin E for 0, 7, 14, or 28 days after arrival. Serum or plasma Fib, Hap, SAA, and AGP concentrations were measured on days 0, 7, and 28 after arrival as well as at the time of treatment for respiratory tract disease with antimicrobial drugs and after completion of treatment.. Vitamin E supplementation was associated with decreased treatment costs. In cattle that were not recognized as sick or responded positively to 1 antimicrobial treatment, serum Hap concentrations were significantly lower on days 0 and 7 than concentrations for cattle that required > 1 treatment. Serum Hap concentrations and ratios of Hap to SAA on day 0 significantly correlated with the number of antimicrobial treatments required. Serum Hap concentrations at the time of initial treatment were significantly lower for cattle that required only 1 treatment, compared with those that required > 1 treatment.. Serum Hap concentrations are of potential value for use in assessing feedlot cattle that may become ill as a result of respiratory tract disease and for use in monitoring treatment efficacy.

Topics: Acute-Phase Proteins; Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Female; Macrolides; Random Allocation; Respiratory Tract Diseases; Thiamphenicol; Tylosin; Vitamin E

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 antimicrobial susceptibility of 55 isolates of Moraxella bovis to seven antibiotics was evaluated by broth microdilution procedures. The isolates had an MIC90 of < or = 1 mg/l to erythromycin, ceftiofur, and ampicillin; 4 mg/l to tilmicosin; 16 mg/l to tylosin and gentamicin; and had MIC90s of > or = 32 mg/l for oxytetracycline. The modal MIC values for these antibiotics were as follows: ampicillin, < 0.25 mg/l; ceftiofur, < or = 0.125 mg/l; tilmicosin, 2 mg/l; tylosin, 8 mg/l; erythromycin 1 mg/l; oxytetracycline, < or = 0.5 mg/l; and gentamicin, < or = 0.5 mg/l. This in vitro data showed most antibiotics have low MICs that are suggestive of clinical efficacy.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Erythromycin; Gentamicins; Keratoconjunctivitis, Infectious; Macrolides; Microbial Sensitivity Tests; Moraxella bovis; Neisseriaceae Infections; Oxytetracycline; Tylosin

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Injections, Subcutaneous; Lung; Macrolides; Male; Mice; Perfusion; Tissue Distribution; Tylosin