tulathromycin and Actinobacillus-Infections

A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)-infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The mean maximum plasma concentration (Cmax ) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for Cmax of tulathromycin in infected pigs was 386 ± 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 ± 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 ± 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half-life t1/2el  = 126 h in plasma and t1/2el  = 165 h in lung, as well as longer drug persistent in infected pigs, was found.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Disaccharides; Heterocyclic Compounds; Lung; Lung Diseases; Swine; Swine Diseases; Tissue Distribution

The aim of this study was the comparison of the tissue pharmacokinetics of tulathromycin in healthy pigs and pigs experimentally infected with Actinobacillus pleuropneumoniae (App). Tulathromycin was given to 24 healthy and 24 infected pigs by intramuscular injection at a single dosage of 2.5 mg kg(-1) body weight (b.w.). Pigs were euthanised at each group and then samples of liver, kidney, muscle, injection site and skin with fat were taken at scheduled time points. Drug concentrations were determined by LC-MS/MS. In this study, higher values of the area under the concentration-time curves (AUC) were calculated in all tissue samples taken from infected than healthy pigs. In pigs with App the AUCs of liver, kidney, muscle, skin with fat and injection site were 1111, 1973, 235, 181 and 2931 mg kg(-1) h, while in pigs without inflammation they were 509, 1295, 151, 111 and 1587 mg kg(-1) h, respectively. Maximum drug tissue concentrations (Cmax) in infected animals were 2370, 6650, 2016, 666 and 83,870 µg kg(-1), while in healthy pigs they were 1483, 6677, 1733, 509 and 55,006 µg kg(-1), respectively. The eliminations half-times (T1/2) were respectively longer in all tissue samples taken from infected animals (from 157.3 to 187.3 h) than in healthy ones (from 138.6 to 161.2 h). The tulathromycin tissue concentrations were significantly higher (p < 0.05) in all tissue samples of the infected pigs compared with the healthy animals at 360 h (from 0.0014 to 0.0280) and at 792 h (from 0.0007 to 0.0242) after drug administration. The results suggest that the tissue pharmacokinetic properties and residue depletion of tulathromycin can be influenced by the disease state of animals.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Case-Control Studies; Disaccharides; Food Analysis; Heterocyclic Compounds; Injections, Intramuscular; Swine; Tissue Distribution

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

To investigate the anti-inflammatory and immunomodulatory properties of tulathromycin in vitro and in experimental models of Actinobacillus pleuropneumoniae-induced pleuropneumonia and zymosan-induced pulmonary inflammation in pigs.. Blood samples from six 8- to 30-week-old healthy male pigs for the in vitro experiment and sixty-five 3-week-old specific pathogen-free pigs.. Neutrophils and monocyte-derived macrophages were isolated from blood samples. Isolated cells were exposed to tulathromycin (0.02 to 2.0 mg/mL) for various durations and assessed for markers of apoptosis and efferocytosis. For in vivo experiments, pigs were inoculated intratracheally with A pleuropneumoniae, zymosan, or PBS solution (control group) with or without tulathromycin pretreatment (2.5 mg/kg, IM). Bronchoalveolar lavage fluid was collected 3 and 24 hours after inoculation and analyzed for proinflammatory mediators, leukocyte apoptosis, and efferocytosis.. In vitro, tulathromycin induced time- and concentration-dependent apoptosis in neutrophils, which enhanced their subsequent clearance by macrophages. In the lungs of both A pleuropneumoniae- and zymosan-challenged pigs, tulathromycin promoted leukocyte apoptosis and efferocytosis and inhibited proinflammatory leukotriene B4 production, with a concurrent reduction in leukocyte necrosis relative to that of control pigs. Tulathromycin also attenuated the degree of lung damage and lesion progression in A pleuropneumoniae-inoculated pigs.. Tulathromycin had immunomodulatory effects in leukocytes in vitro and anti-inflammatory effects in pigs in experimental models of A pleuropneumoniae infection and nonmicrobial-induced pulmonary inflammation. These data suggested that in addition to its antimicrobial properties, tulathromycin may dampen severe proinflammatory responses and drive resolution of inflammation in pigs with microbial pulmonary infections.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Inflammatory Agents; Apoptosis; Disaccharides; Heterocyclic Compounds; Leukocytes; Leukotriene B4; Male; Phagocytosis; Pneumonia, Bacterial; Specific Pathogen-Free Organisms; Swine; Swine Diseases; Zymosan

The effect of a single or double dose of tulathromycin was evaluated in pigs carrying Actinobacillus pleuropneumoniae serotype 2 in their tonsils. Twenty-nine pigs from a reinfected specific pathogen-free-herd were selected from animals testing positive in an A pleuropneumoniae serotype 2-specific pcr test on tonsil scrapings and they were divided into three groups. The pigs in group 1 were treated subcutaneously with 2.5 mg/kg tulathromycin on day 0, the pigs in group 2 were treated with 2.5 mg/kg tulathromycin on days 0 and 4, and the pigs in group 3 were left untreated as controls. The pigs were tested by pcr on tonsil scrapings on days 0, 4, 11 and 33, and on day 33 all the animals were euthanased. There were no significant differences between the numbers of PCR-positive animals in the three groups on any of the sampling dates.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Carrier State; Denmark; Disaccharides; Heterocyclic Compounds; Microbial Sensitivity Tests; Palatine Tonsil; Polymerase Chain Reaction; Swine; Swine Diseases