Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1)
Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg
tilmicosin per kg
body weight (n = 12). Calves that were non-infected and
tilmicosin-treated were also included for determining
tilmicosin concentrations 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 monitored clinically. Serum samples were collected for determination of
tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of
tilmicosin.
Tilmicosin treated animals responded significantly better to
therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that
tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy
tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the
tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum
tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations 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 concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected
tilmicosin-treated animals (P < 0.05). These data demonstrate that
tilmicosin was effective in treating experimentally-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.