None of the calves treated with gamithromycin showed any systemic or local adverse reactions or signs of toxicity.
The values for the main pathological, clinical, and bacteriological observations for individual calves are listed in Table . Between challenge and scheduled necropsy (day 10), three animals died or were euthanized in extremis with severe clinical signs of acute respiratory disease, two from group 4 and one from group 1. At necropsy, all three animals were confirmed as having pneumonic lesions with M. haemolytica counts on culture. All other animals survived to scheduled necropsy on day 10.
Individual lung lesion scores, clinical scores, and recovery of M. haemolytica
The distributions of rectal temperatures in all groups on the morning prior to challenge were very similar (with means of approximately 38.4°C). Postchallenge, there was a significant difference in the pattern of responses over time between the four groups (P < 0.001 for the group × time interaction effect). The mean temperature in all groups increased by 1.06°C to 1.83°C over the immediate 12-h period postchallenge but had dropped by the next morning after the challenge; however, the mean temperature in untreated controls (group 4) remained above the base level for most of the remainder of the study, whereas animals treated on day −1 (group 3) had close to a normal mean temperature from day 2 onwards.
The distributions of respiratory rates in all groups on the morning prior to challenge were very similar (means of approximately 35 breaths per minute). Postchallenge, there was strong evidence of a significant difference in the pattern of responses over time between the four groups (P < 0.001 for the group × time interaction effect). There was a sharp rise in the mean respiration rate on the day of challenge in all four groups to 72 to 93 breaths per minute; thereafter, the pattern of responses was inconsistent, although animals treated on day −1 (group 3) generally had the lowest mean respiratory rate.
The mean total clinical score postchallenge was calculated for each calf. To avoid a bias caused by the early euthanasia of some calves, the mean score was calculated for the period from the afternoon of the day of challenge (day 0 p.m.) to the morning of day 2. A one-way analysis of variance was carried out on the group mean scores. The means and patterns of clinical responses over this period were similar for treated groups 1, 2, and 3 (Table ), and these were lower than the mean scores for group 4, the untreated controls (P = 0.03). This pattern was similar for the component measures of the total clinical score: respiration, coughing, nasal discharge, and demeanor.
Mean clinical scores, lung lesion scores, and number of animals in each group positive for M. haemolytica postchallenge
The lung lesion score (percent lung lesions) of one animal from group 1 was not assessed or recorded at necropsy in error. A photograph (not shown) of this animal's lungs taken immediately after necropsy showed little evidence of lung pathology; hence, it can be assumed that the means for group 1 have not been underestimated as a consequence of this calf's data being absent from the analyses. The data for this animal were excluded from the statistical analysis of lung lesion scores but were included in all other analyses. A summary of the estimated lung lesion scores (percent lung lesions) for each group is given in Table .
The lung lesion scores were not consistent within each group of calves, with untreated controls (group 4) in particular showing considerable variability (Table ). The scores for each group were skewed to the right, with the standard deviation approximately the same size as the mean for each group; consequently, there was no formal statistical evidence (P = 0.76) of any differences in mean responses between the four groups (Table ).
The number of M. haemolytica CFU/g lung tissue was estimated for samples taken from four regions of each lung. Individual animals within a group had variable counts, and of the 37 animals in total, 19 animals had no bacteria recovered from any of the samples. There was no evidence of a difference in mean counts between the different areas of the lung, and a mean count, on a log scale using the transformation log10(count + 1), was calculated for each animal. The numbers of animals in each group from which M. haemolytica was recovered in at least one sample are shown in Table . Using a Fisher's exact test, there was a significant difference (P = 0.0008) in the proportion of animals with positive counts between the groups. M. haemolytica was recovered from all the untreated control animals (group 4), whereas only one of the nine animals treated on day −1 (group 3) had a positive count.