Tomazi A C C H, Tomazi T, Bringhenti L, Vinhal A P A, Rodrigues M X, Bilby T R, Huson H J, Bicalho R C
Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853.
Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853; Merck Animal Health, Madison, NJ 07940.
J Dairy Sci. 2023 Apr;106(4):2750-2771. doi: 10.3168/jds.2022-22451. Epub 2023 Feb 14.
The aim of this study was to evaluate the effect of therapeutically administered tildipirosin or florfenicol + flunixin meglumine for the treatment of bovine respiratory disease (BRD) accompanied by fever in calves before weaning compared with diseased and untreated animals. As specific objectives, we evaluated the composition of the bacterial microbiota of the upper respiratory tract (URT) and blood and health parameters of the animals. Preweaning Holstein female calves diagnosed with naturally acquired pneumonia were randomly assigned to one of the following experimental groups on the day of diagnosis (d 0): (1) TLD (n = 36): single subcutaneous injection with 4 mg/kg tildipirosin; (2) FLF (n = 33): single subcutaneous injection with an antimicrobial (40 mg/kg florfenicol) combined with a nonsteroidal anti-inflammatory drug (2.2 mg/kg flunixin meglumine); and (3) NEG (n = 35): no treatment within the first 5 d following enrollment. The NEG treatment group was closely monitored for 5 d, and calves were removed from the study following a standardized late treatment protocol, when necessary, to minimize health concerns. Healthy untreated calves (CTR; n = 31) were also selected for the study and used as controls. Blood samples used for biochemical analysis and nasopharyngeal swabs used for evaluation of URT microbiota were collected daily from d 0 until d 5 and then weekly until weaning. Next-generation sequencing of the 16S rRNA gene was used to assess the URT microbiota at the phylum and genus levels. Clinical signs associated with pneumonia and otitis media were assessed daily, as was the need for antibiotic interventions. Calves in the TLD and FLF groups had faster recovery from fever within the first 5 d after enrollment. In addition, antibiotic-treated calves reached the same serum haptoglobin levels as healthy calves on d 2 after diagnosis, whereas calves in the NEG group had higher haptoglobin levels than the CTR group until at least d 5 after BRD diagnosis. Calves in the TLD and FLF groups had a lower risk of treatment for pneumonia (FLF = 22.8%; TLD = 27.7%) from d 5 to weaning than calves in the NEG group (54.7%). Furthermore, FLF treatment had a significantly lower risk of nasal discharge, otitis media, and treatment failure compared with the NEG group, but did not differ from the TLD group. Differences in the composition of the URT microbiota were found between groups, and the genus Mycoplasma was the most abundant in samples collected from the URT of calves with and without pneumonia. Both drugs were effective in reducing the mean relative abundance (MRA) of important genera associated with pneumonia (Mannheimia and Pasteurella), although an increase in Mycoplasma MRA was observed for tildipirosin-treated calves. In conclusion, both drugs were effective in reducing the inflammatory signs of pneumonia and the need for antimicrobial treatment after enrollment compared with no treatment. In addition, both TLD and FLF were effective in reducing the MRA of important bacterial genera associated with pneumonia; however, TLD treatment was associated with increased Mycoplasma MRA compared with healthy and untreated calves.
本研究的目的是评估治疗性给予替地米星或氟苯尼考 + 氟尼辛葡甲胺对断奶前伴有发热的犊牛患牛呼吸道疾病(BRD)的治疗效果,并与患病但未治疗的动物进行比较。作为具体目标,我们评估了动物上呼吸道(URT)和血液的细菌微生物群组成以及健康参数。在诊断当天(第0天),将诊断为自然获得性肺炎的断奶前荷斯坦雌性犊牛随机分配到以下实验组之一:(1)TLD组(n = 36):皮下注射4 mg/kg替地米星;(2)FLF组(n = 33):皮下注射抗菌药物(40 mg/kg氟苯尼考)联合非甾体抗炎药(2.2 mg/kg氟尼辛葡甲胺);(3)NEG组(n = 35):入组后的前5天不进行治疗。对NEG治疗组密切监测5天,必要时按照标准化的延迟治疗方案将犊牛从研究中剔除,以尽量减少健康问题。还选择了健康未治疗的犊牛(CTR组;n = 31)作为对照进行研究。从第0天到第5天每天采集用于生化分析的血液样本和用于评估URT微生物群的鼻咽拭子,然后每周采集一次直至断奶。使用16S rRNA基因的下一代测序技术在门和属水平评估URT微生物群。每天评估与肺炎和中耳炎相关的临床症状以及抗生素干预的必要性。TLD组和FLF组的犊牛在入组后的前5天内发热恢复更快。此外,抗生素治疗的犊牛在诊断后第2天达到了与健康犊牛相同的血清触珠蛋白水平,而NEG组的犊牛在BRD诊断后至少第5天的触珠蛋白水平高于CTR组。从第5天到断奶,TLD组和FLF组的犊牛患肺炎的治疗风险(FLF = 22.8%;TLD = 27.