Tulathromycin: an overview of a new triamilide antibiotic for livestock respiratory disease.

Tulathromycin is a novel triamilide antimicrobial that has been approved for use in the treatment and prevention of bovine respiratory disease and the treatment of swine respiratory disease in the European Union and the United States. The agent penetrates gram-negative bacteria well, and it exhibits mixed bacteriostatic and bactericidal activity. Tulathromycin is formulated as a ready-to-use, sterile aqueous solution, and the packaged concentration of 100 mg tulathromycin/ml allows low-volume dosing. This agent is characterized by rapid absorption from the injection site, extensive distribution to tissue, and slow elimination, thereby providing high, prolonged drug concentration in the lungs. Studies show that a single dose of tulathromycin is effective in treating cattle and swine with respiratory disease and in preventing high-risk cattle from developing respiratory disease.

Efficacy of tulathromycin in the treatment and prevention of natural outbreaks of bovine respiratory disease in European cattle.

The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2) of bovine respiratory disease (BRD) was evaluated on commercial farms in France, Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar percentages of animals showed sustained clinical improvement at day 14 (tulathromycin 83.3% versus florfenicol 81.0%) and had not relapsed by day 60 (tulathromycin 63.3% versus florfenicol 58.4%). In phase 2, healthy in-contact cattle were treated with tulathromycin (n = 492), tilmicosin (n = 494), or saline (n = 265) on day 0. Significantly more (P = .0001) tulathromycin-treated cattle remained healthy to day 14 (92.4%) than tilmicosin-treated (83.7%) or saline-treated (63.7%) cattle, and this was maintained through day 60 (tulathromycin 85.4% versus tilmicosin 75.1% and saline 56.2%). Tulathromycin was highly effective in the treatment and prevention of BRD.

In vitro microbiological characterization of a novel azalide, two triamilides and an azalide ketal against bovine and porcine respiratory pathogens.

Several novel 15-membered-ring macrolide agents (azalide 1, triamilides 2 and 3, and the azalide 3,6-ketal 4) were identified as potential antibacterial agents against Mannheimia (formerly named as Pasteurella) haemolytica, Pasteurella multocida, Haemophilus somnus and Actinobacillus pleuropneumoniae, important etiological agents of bovine and porcine respiratory disease. Compound 3 is the major component of the antibiotic tulathromycin. Antibacterial activity against tilmicosin-resistant P. multocida field isolates was also tested. In vitro MIC 50/90 analysis revealed that the four newly synthesized compounds were more potent than tilmicosin against M. haemolytica (4 to approximately 8x), P. multocida (8 to approximately 16x), A. pleuropneumoniae (4x), H. somnus (2x and 16x), and tilmicosin-resistant P. multocida (32x). In time-kill kinetic studies, all four novel compounds and tilmicosin showed bactericidal activity against M. haemolytica, P. multocida and A. pleuropneumoniae at both 4x and 8x MIC. A functional assay using genetically defined mutants revealed that all four novel compounds were poorer substrates for the efflux pump, AcrA/B system, than tilmicosin. A pH study using LPS mutants indicated that the enhanced in vitro potency of the triamilides, particularly compound 3 was mainly due to better penetration of the molecule through the outer membrane. The third amine group at the C-4'' position of the triamilde molecules contributed to this increased membrane penetration by increasing overall basicity. These studies indicate that the four novel compounds have potential as antibacterial agents against bovine and porcine respiratory disease.

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas.

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.