TREATMENT OF EXPERIMENTALLY-INDUCED PNEUMONIC PASTEURELLOSIS OF YOUNGCALVES WITH TILMICOSIN

Twenty four (24) healthy male Holstein calves (< 70 kg) were each expe rimentally infected by intrabronchial inoculation of 4.0 x 10(9) viabl e cells of Pasteurella haemolytica-A1 (B122) at Time = 0 h. At 1 h fol lowing inoculation animals received either: 1) Sham treatment with ste rile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmi cosin per kg body weight (n = 12). Calves that were non-infected and t ilmicosin-treated were also included for determining tilmicosin concen trations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h ( n = 3 per time). In the infected calves, response to therapy was monit ored clinically. Serum samples were collected for determination of til micosin concentrations using HPLC. Any animal becoming seriously ill w as humanely killed. Complete necropsy examinations were performed on a ll animals and included gross pathologic changes, bacteriologic analys is, histopathology, and determination of pulmonary concentrations of t ilmicosin. Tilmicosin treated animals responded significantly better t o therapy than saline-treated control calves. Clinical assessment of c alves during the study indicated that tilmicosin-treated calves had si gnificantly improved by T = 8 h compared to saline-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tiss ue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemo lytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0 /12) cultured positive for P. haemolytica, Mean (+/- standard error) s erum tilmicosin concentrations in infected calves peaked at 1 h post-i njection (1.10 +/- 0.06 mu g/mL) and rapidly decreased to 0.20 +/- 0.0 3 mu g/mL, well below the MIC of 0.50 mu g/mL for P. haemolytica-A1 (B 122), by 12 h. These serum concentrations were very similar to serum c oncentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentr ations at 72 h were significantly higher in experimentally infected ca lves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experiment ally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight .