Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853-6401.
Merck Animal Health, Madison, NJ 07940.
J Dairy Sci. 2021 Sep;104(9):10291-10309. doi: 10.3168/jds.2020-19945. Epub 2021 Jun 5.
The objective of this randomized clinical study was to compare the effect of 2 antimicrobial interventions, tildipirosin or florfenicol + flunixin meglumine, used for treatment of pneumonia and extralabel treatment for otitis on health parameters and upper respiratory tract (URT) microbiota of preweaned Holstein calves. Housed preweaned Holstein heifers diagnosed with either otitis or pneumonia were assigned into 1 of 2 treatment groups, receiving a single subcutaneous injection of either 4 mg/kg of tildipirosin (TLD; n = 444) or 40 mg/kg of florfenicol combined with 2.2 mg/kg of a nonsteroidal anti-inflammatory, flunixin meglumine (FLF; n = 442). Calves were enrolled and treated on the day of diagnosis of the first case of pneumonia or otitis. If a calf had a recurrent case, the opposite drug was administered, respecting an interval of 5 d between drug injections. Blood samples for leukocyte counts were collected at 0, 2, 4, and 6 d after treatment, and rectal temperature was measured daily during the 5 d after treatment. Ear scores were observed from calves with otitis. Additionally, swabs of the URT were collected from a subset of 20 calves in each treatment group at d 0, 3, 6, 9, and 11 following enrollment for analysis of URT microbiota through next-generation sequencing of the 16S rRNA gene and quantitative PCR. Swabs were also collected from a comparative group of 20 healthy calves that did not receive any drug. No differences were observed between groups for recurrence risk of either pneumonia (TLD = 32.4%; FLF = 29.7%) or otitis (TLD = 72.7%; FLF = 73.6%). Similarly, no differences were observed for the total number of treatments for pneumonia (TLD = 1.45; FLF = 1.42) or otitis (TLD = 2.96; FLF = 3.07). On the other hand, both drugs reduced rectal temperature, ear scores, and leukocyte counts, with FLF calves having a greater reduction in rectal temperature within 4 d after treatment. Both TLD and FLF reduced the total bacterial load when compared with healthy untreated calves, but no differences were observed between treatment groups. Furthermore, compared with the untreated group, treated calves had lower mean relative abundances (MRA) of the genera Mannheimia, Moraxella, and Pasteurella within 11, 9, and 3 d after treatment, respectively; however, no significant differences were observed between TLD and FLF. On the other hand, MRA of Mycoplasma was not decreased by both treatments compared to untreated animals, and a higher MRA was observed in the TLD group during 11 d after treatment in comparison to FLF and untreated calves. Based on this data, we concluded that both drugs used in the study were effective in reducing rectal temperature, ear scores, leukocyte counts, and MRA of the genera Mannheimia, Pasteurella, and Moraxella in the URT, and calves treated with FLF had a greater reduction in rectal temperature.
本随机临床试验的目的是比较两种抗菌干预措施——替米考星或氟苯尼考+氟尼辛葡甲胺——在治疗肺炎和超说明书治疗中耳炎方面的效果,以及对未断奶荷斯坦小牛的健康参数和上呼吸道(URT)微生物群的影响。患有中耳炎或肺炎的圈养未断奶荷斯坦小母牛被分配到 2 个治疗组中的 1 个,接受单剂量皮下注射 4mg/kg 的替米考星(TLD;n=444)或 40mg/kg 的氟苯尼考与 2.2mg/kg 的非甾体抗炎药氟尼辛葡甲胺(FLF;n=442)。小牛在肺炎或中耳炎的首例病例确诊当日入组并接受治疗。如果小牛出现复发病例,则给予相反的药物,但两种药物之间需间隔 5d。在治疗后 0、2、4 和 6d 时采集白细胞计数的血液样本,并在治疗后 5d 内每天测量直肠温度。对患有中耳炎的小牛进行耳部评分观察。此外,在入组后第 0、3、6、9 和 11d,从每组 20 头小牛中采集 URT 拭子,通过下一代测序 16S rRNA 基因和定量 PCR 分析 URT 微生物群,用于分析 URT 微生物群。还从未接受任何药物的 20 头健康小牛的对照组中采集拭子。肺炎(TLD=32.4%;FLF=29.7%)或中耳炎(TLD=72.7%;FLF=73.6%)的复发风险在组间无差异。同样,肺炎(TLD=1.45;FLF=1.42)或中耳炎(TLD=2.96;FLF=3.07)的总治疗次数也无差异。另一方面,两种药物均降低了直肠温度、耳部评分和白细胞计数,FLF 治疗的小牛在治疗后 4d 内直肠温度下降更大。与未接受治疗的健康小牛相比,替米考星和氟苯尼考均降低了总细菌负荷,但组间无差异。此外,与未治疗组相比,治疗后的小牛在治疗后 11、9 和 3d 时,曼海姆菌、莫拉氏菌和巴氏杆菌的平均相对丰度(MRA)分别降低;然而,替米考星和氟苯尼考之间无显著差异。另一方面,与未治疗动物相比,两种治疗均未降低支原体的 MRA,并且与氟苯尼考和未治疗小牛相比,替米考星组在治疗后 11d 时的 MRA 更高。基于这些数据,我们得出结论,研究中使用的两种药物均有效降低了直肠温度、耳部评分、白细胞计数以及 URT 中曼海姆菌、巴氏杆菌和莫拉氏菌的 MRA,并且氟苯尼考治疗的小牛直肠温度下降更大。