Effect of metaphylactic administration of tildipirosin on the incidence of pneumonia and otitis and on the upper respiratory tract and fecal microbiome of preweaning Holstein calves

The objectives of this study were to evaluate the effect of the metaphylactic use of a semi-synthetic long-acting macrolide (tildipirosin) on the prevention of pneumonia and otitis in preweaning Holstein calves, as well as its effects on the microbiome of their upper respiratory tract (URT) and feces. Newborn healthy Holstein heifers, collectively housed, were randomly allocated to 1 of 2 treatment groups: treatment (TRT; n = 932) or control (CTR; n = 927). Calves in the TRT group received a single subcutaneous injection of 4 mg/kg tildipirosin (Zuprevo, Merck Animal Health) at 7 +/- 7 d of life. Calves in the CTR group received no drug injection. All enrolled calves were evaluated from 1 to 63 +/- 3 d of life (weaning age) and monitored daily for any adverse health events during this period. Daily physical examination was performed to diagnose pneumonia and otitis, and body weight was measured weekly in all animals. From a randomly selected subset of 217 calves, blood samples for biochemical variables analysis and swabs were collected weekly from the URT and rectum for analysis of the nasal and fecal micro biome, respectively, via next-generation sequencing of the 16S rRNA gene. Total bacterial load was evaluated using quantitative PCR. In addition, another subset of 26 calves was randomly selected and fecal swabs were collected in a more intensive sampling to investigate the short-term effect of tildipirosin administration on the fecal microbiome. We performed general mixed linear models and logistic regression to analyze continuous and binary outcomes, respectively. Tildipirosin metaphylaxis reduced the incidence of otitis (CTR = 47.03%; TRT = 37.55%) and tended to reduce the incidence of pneumonia (CTR = 20.71%; TRT = 17.38%) and the overall mortality risk (CTR = 6.69%; TRT = 4.94%). We observed no significant differences between groups for mortality due to pneumonia (CTR = 0.86%; TRT = 0.97%) or mortality due to otitis (CTR = 2.05%; TRT = 1.39%). Calves in the TRT group had a higher average daily gain than calves in the CTR group. Furthermore, metaphylaxis had no significant effects on the total bacterial load, genus, or phylum analysis of the fecal microbiome from the 2 subset groups. However, for the URT microbiota, we observed a significant decrease in total bacterial load for the TRT group compared to the CTR group 1 week after metaphylactic injection. Tildipirosin metaphylaxis decreased the mean relative abundance of the genera Mannheimia, Moraxella, and Pasteurella but significantly increased the mean relative abundance of Mycoplasma. Although tildipirosin had no positive effect on Mycoplasma, it reduced the mean relative abundance of important pathogenic bacteria in the URT and had positive effects for the control of otitis. The metaphylactic use of tildipirosin can be a suitable strategy for the control of otitis on farms with a high prevalence of this disease.