tulathromycin and ceftiofur

Antibiotic use in cattle can select for multidrug-resistant

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Disaccharides; Feces; Heterocyclic Compounds; Lymph Nodes; Population Dynamics; Salmonella enterica; Skin

This study assessed the dynamics of cephalosporin resistant (CR) E. coli populations during the life cycle of pigs treated early in life with ceftiofur or tulathromycin. The study was conducted at eight conventional pig farms; four for each treatment with ceftiofur or tulathromycin. At each farm, 70 7-day-old piglets were divided into two groups: a control group (n = 30) and a treatment group (n = 40). Faecal samples were collected on day 0 and on days 2, 7 and 180 post-treatment. Sows were also sampled on day 0. CR E. coli were selected on MacConkey agar with ceftriaxone. On five farms, 7-day-old piglets excreted CR E. coli before treatment associated with the presence of CR E. coli in sows. The occurrence of CR E. coli positive animals decreased with increasing piglet age. The remaining three farms tested negative for CR E. coli during the study period. Results demonstrated great variability in the frequency of CR E. coli positive animals between farms, independent of treatment. Treatment with ceftiofur resulted in a transitory increase in the counts of CR E. coli after 48 h. However, other risk factors including the presence of CR E. coli in sows and animal age were more important than antimicrobial treatment. Accordingly, intervention strategies targeting sows would likely have a beneficial effect in reducing the occurrence of antimicrobial resistance in primary pig production.

Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; Bacterial Shedding; Cephalosporin Resistance; Cephalosporins; Disaccharides; Escherichia coli; Escherichia coli Infections; Feces; Heterocyclic Compounds; Risk Factors; Spain; Swine; Swine Diseases

In this field trial, a new combination product containing florfenicol and flunixin meglumine (FLOR-FM) was compared with commercially available products that contained only tulathromycin (TULA) or ceftiofur crystalline free acid (CCFA) for the treatment of undifferentiated fever (UF; rectal temperature >/=105.0 degrees F) in beef calves that received long-acting oxytetracycline at feedlot arrival. The overall mortality rate of the FLOR FM group (2.0%) was significantly (P less than .050) lower than the rates in the TULA and CCFA groups (10.0% and 20.0%, respectively; 50 animals/group), even though the first UF relapse rate of the FLOR FM group was significantly (P less than .050) higher than that of the TULA group. In the FLOR FM group, this resulted in per-animal economic advantages of Can$46.23 (versus TULA) and Can$108.77 (versus CCFA) based on equal costs for initial UF therapy. These results demonstrate that it is more cost-effective to administer FLOR FM than TULA or CCFA for initial UF therapy in feedlot calves at high risk for bovine respiratory disease that receive metaphylactic long-acting oxytetracycline at feedlot arrival.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cattle Diseases; Cephalosporins; Clonixin; Disaccharides; Drug Combinations; Fever; Heterocyclic Compounds; Housing, Animal; Thiamphenicol

A total of 894 calves at high risk for bovine respiratory disease were processed at two sites and randomly assigned to receive one of three antimicrobial metaphylactic regimens to determine if a two-drug regimen offered any advantage over the more conventional one-course regimens. On arrival, calves received either a two-course regimen of ceftiofur crystalline free acid (CCFA) followed by tulathromycin 8 days later (Group 1) or a one-course regiment of CCFA (Group 2) or tilmicosin (Group 3). At Site A, morbidity was significantly lower (52%) in Group 1 than in Group 2 (76.3%) and Group 3 (78.4%). At Site B, morbidity was significantly lower in Group 1 (2.6%) than in Group 2 (9.4%) and Group 3 (7.2%).

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Drug Therapy, Combination; Heterocyclic Compounds; Male; Risk Factors; Treatment Outcome

The efficacy of a single dose of tulathromycin, a novel triamilide antimicrobial of the macrolide class, given at 2.5 mg/kg or 5 mg/kg bodyweight, or three daily doses of ceftiofur, given at 3 mg/kg bodyweight, was evaluated in pigs with respiratory disease induced experimentally with Actinobacillus pleuropneumoniae. On day 0, 100 pigs with clinical signs of respiratory disease were randomly assigned to groups of 25 pigs, which were treated with either saline, one of the doses of tulathromycin, or ceftiofur. The pigs' rectal temperatures and clinical scores for respiratory signs and general attitude were recorded daily until day 10. Animals withdrawn from the study for welfare reasons were recorded. On day 10, the animals remaining in the study were weighed, euthanased and examined postmortem. Three of the animals treated with saline and one of those treated with 2.5 mg/kg tulathromycin were withdrawn from the study, but none of those treated with 5 mg/kg tulathromycin or ceftiofur were withdrawn. The least squares mean bodyweight gains of the pigs treated with the antimicrobial agents were significantly (P<0.05) higher than that of the saline-treated group, and the least squares mean percentages of the total lung involvement and incidence of respiratory disease associated with A. pleuropneumoniae were significantly (P<0.05) lower, but there were no significant differences between the three groups of pigs treated with the antimicrobial agents.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Infective Agents; Cephalosporins; Disaccharides; Heterocyclic Compounds; Linear Models; Lung; Male; Swine; Swine Diseases; Treatment Outcome

Tulathromycin, a novel triamilide antimicrobial, was evaluated for treatment of swine respiratory disease (SRD) in field efficacy studies involving 720 pigs in six North American swine herds. In each study, feeder pigs with clinical SRD were randomly assigned in equal numbers to a group treated with tulathromycin given as a single injection at 2.5 mg/kg of body weight or to a saline-treated control group. Four of the studies included a third group treated with ceftiofur sodium for 3 consecutive days at 3 mg/kg of body weight. Pigs were treated on day 0 and evaluated for treatment response on day 7. In each study, 10 or more nontreated pigs and saline-treated pigs that did not respond to treatment underwent necropsies to obtain lung samples that were evaluated for SRD pathogens. The overall cure rate was 46.4% for saline-treated pigs, 71.1% for tulathromycin-treated pigs, and 63.1% for ceftiofur-treated pigs. The cure rate for tulathromycin-treated pigs was significantly higher than for saline-treated pigs (P = .0116). Mortality from SRD occurred in 24 control pigs, seven tulathromycin-treated pigs, and one ceftiofur-treated pig. The mortality rate was significantly lower for both the tulathromycin- and ceftiofur-treated pigs compared with those treated with saline (P = .0148 and P = .0195, respectively). Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Mycoplasma hyopneumoniae, bacteria commonly associated with SRD, were isolated from SRD-affected pigs. Under field conditions, tulathromycin injectable solution given as a single IM dose of 2.5 mg/kg of body weight was safe and effective in the treatment of SRD.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Disaccharides; Female; Gram-Negative Bacteria; Heterocyclic Compounds; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Mycoplasma hyopneumoniae; Pasteurellosis, Pneumonic; Severity of Illness Index; Swine; Swine Diseases; Treatment Outcome; United States

The nasal microbiota plays an important role in animal health and the use of antibiotics is a major factor that influences its composition. Here, we studied the consequences of an intensive antibiotic treatment, applied to sows and/or their offspring, on the piglets' nasal microbiota. Four pregnant sows were treated with crystalline ceftiofur and tulathromycin (CT

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Bacteria; Female; Humans; Lactation; Microbiota; Pregnancy; Swine

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

While antimicrobials are cost-effective tools for prevention and treatment of infectious disease, the impact of their use on potentially beneficent mucosal microbial communities of growing pigs has not been widely explored. The objective of this study was to characterize the impact of parenteral antibiotics administration on the composition and diversity of the resident fecal microbiota in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Oxytetracycline (OTC), Procaine Penicillin G (PPG) and Tulathromycin (TUL) at label dose and route. Individual fecal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. Genomic DNA was extracted, and the V1-V3 hypervariable region of 16S rRNA gene was amplified and sequenced using Illumina Miseq-based sequencing. Across all groups, the most abundant phyla were Firmicutes, Bacteroidetes, and Proteobacteria. Linear discriminant analysis and stacked area graphs, showed a pronounced, antimicrobial-dependent shift in the composition of fecal microbiota over time from day 0. By day 14, the fecal microbial compositions of the groups receiving CHC and TUL had returned to a distribution that closely resembled that observed on day 0, but differences were still evident. In contrast, animals that received PPG, OTC and CCFA, showed a tendency towards a balanced homeostatic microbiota structure on day 7, but appeared to deviate away from the day 0 composition by day 14. Based on our results, the observed changes in fecal microbiota showed antimicrobial-specific variation in both duration and extent. Understanding the impact of these important antimicrobial-induced changes will be a critical step in optimizing the use of antimicrobials in health management programs in the swine industry.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Biodiversity; Cephalosporins; Disaccharides; DNA, Bacterial; Drug Combinations; Feces; Heterocyclic Compounds; Microbial Consortia; Microbiota; Molecular Sequence Data; Oxytetracycline; Penicillin G; Penicillin G Procaine; Phylogeny; RNA, Ribosomal, 16S; Swine; Time Factors

The continuous administration of antimicrobials in swine production has been widely criticized with the increase of antimicrobial-resistant bacteria and dysbiosis of the beneficial microbial communities. While an increasing number of studies investigate the effects of antimicrobial administration on swine gastrointestinal microbiota biodiversity, the impact of their use on the composition and diversity of nasal microbial communities has not been widely explored. The objective of this study was to characterize the short-term impact of different parenteral antibiotics administration on the composition and diversity of nasal microbial communities in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Tulathromycin (TUL), Oxytetracycline (OTC), and Procaine Penicillin G (PPG) at label dose and route. Individual deep nasal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. The nasal microbiota across all the samples were dominated by Firmicutes, proteobacteria and Bacteroidetes. While, the predominant bacterial genera were Moraxella, Clostridium and Streptococcus. Linear discriminant analysis, showed a pronounced, antimicrobial-dependent microbial shift in the composition of nasal microbiota and over time from day 0. By day 14, the nasal microbial compositions of the groups receiving CCFA and OTC had returned to a distribution that closely resembled that observed on day 0. In contrast, pigs that received CHC, TUL and PPG appeared to deviate away from the day 0 composition by day 14. Based on our results, it appears that the impact of parenteral antibiotics on the swine nasal microbiota is variable and has a considerable impact in modulating the nasal microbiota structure. Our results will aid in developing alternative strategies for antibiotics to improve swine health and consequently production.

Topics: Animals; Animals, Newborn; Anti-Infective Agents; Bacteroidetes; Cephalosporins; Clostridium; Disaccharides; Discriminant Analysis; DNA, Bacterial; Dose-Response Relationship, Drug; Firmicutes; Heterocyclic Compounds; Microbiota; Moraxella; Nose; Oxytetracycline; Penicillin G Procaine; Proteobacteria; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Streptococcus; Swine

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points.

Topics: Animals; Anti-Bacterial Agents; Biological Availability; Cattle; Cephalosporins; Cross-Over Studies; Disaccharides; Enrofloxacin; Epithelial Cells; Extracellular Fluid; Fluoroquinolones; Heterocyclic Compounds; Lung; Male; Mannheimia haemolytica; Microbial Sensitivity Tests; Respiratory Mucosa; Thiamphenicol; Veterinary Drugs

It addition to their antimicrobial properties, antibiotics can influence the host immune system (modulation of cytokine secretion, antibody production and T-cell proliferation). In the present study, the authors studied the effects of therapeutic doses of amoxicillin (AMX), ceftiofur (CEF), doxycycline (DOXY), tiamulin (TIAM) and tulathromycin (TUL) on the postvaccinal immune response after pigs had been vaccinated against erysipelas. Because humoral immunity is considered as the most important in the protection against swine erysipelas, the present study focused on the interactions between antibiotics and postvaccinal humoral immunity. One hundred and five, eight-week-old pigs of both sexes were used. Specific antibodies to the Erysipelothrix rhusiopathiae antigen were determined using a commercial ELISA test. In pigs treated with DOXY or CEF or TIAM, a significant reduction in the number of positive pigs was observed four and six weeks after the second dose of vaccine, compared with the remaining vaccinated groups. In pigs treated with CEF, the ELISA score was significantly lower than in non-treated vaccinated pigs. While in vaccinated pigs treated with AMX or TUL, the ELISA score was significantly higher than in pigs treated with the remaining antibiotics and than in non-treated vaccinated controls. The results of the present study indicate that vaccination of pigs against erysipelas in the presence of antibiotics may result in a decrease (CEF, DOXY, TIAM) or enhancement (AMX, TUL) in the production of specific antibodies.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Bacterial Vaccines; Cephalosporins; Disaccharides; Diterpenes; Doxycycline; Female; Heterocyclic Compounds; Immunity, Humoral; Male; Swine; Swine Erysipelas

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 purpose of this study was to determine the activities of two antibacterial agents used in the treatment of bovine respiratory infections-tulathromycin, a macrolide, and ceftiofur, a third-generation cephalosporin-alone, in combination with each other, and in combination with each of seven additional antibiotics (tilmicosin, florfenicol, enrofloxacin, danofloxacin, ampicillin, tetracycline, and penicillin G) against bovine Pasteurella multocida (n = 60) and Mannheimia haemolytica (n = 10) isolates for determination of synergy, antagonism, or indifference. Of 458 organism-drug combinations, 160 combinations of tulathromycin and 209 combinations of ceftiofur with eight antimicrobial drugs were indifferent. One combination was antagonistic (ceftiofur + florfenicol against one isolate of P. multocida). Time-kill studies showed loss of cidality for ceftiofur when combined with florfenicol at 1x the minimal inhibitory concentration. Overall, the in vitro data demonstrated that tulathromycin and ceftiofur, in combination with each other or seven other antimicrobial agents, primarily produce an indifferent response with no occurrences of synergism and rare occurrences of antagonism.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Cephalosporins; Disaccharides; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Heterocyclic Compounds; Mannheimia haemolytica; Microbial Sensitivity Tests; Pasteurella multocida; Time Factors; Treatment Outcome

This study demonstrated the ability of the antimicrobials tulathromycin (Draxxin) and ceftiofur crystalline free acid sterile suspension (Excede) to clear the spirochete Leptospira borgpetersenii serovar hardjo type hardjo-bovis (L. hardjo-bovis) from experimentally infected cattle. Treatment with tulathromycin resulted in clearance of L. hardjo-bovis organisms from the urine and kidney tissue of all animals (9 of 9), and treatment with ceftiofur crystalline free acid resulted in clearance of the organisms from the urine of 8 of 10 heifers and the kidney tissue of all 10 animals. In contrast, 10 of 10 placebo-treated cattle had L. hardjo-bovis organisms in their urine and 8 of 10 had the organisms in kidney tissue.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Cephalosporins; Disaccharides; Female; Heterocyclic Compounds; Leptospira; Leptospirosis; Random Allocation; Treatment Outcome