Scientia Agricultura Sinica ›› 2019, Vol. 52 ›› Issue (16): 2899-2911.doi: 10.3864/j.issn.0578-1752.2019.16.015

• ANIMAL SCIENCE·VETERINARY SCIENCE·RESOURCE INSECT • Previous Articles     Next Articles

Antibacterial Activity in Vitro and Protection of Tildipirosin Injection Against Artificially Infected Haemophilus Paracoides in Piglets

LI GuoJi1,YAN ChaoQun1,MA YuQiao1,XIE Shun1,GU Xin2,CAO Ying2,HUANG ShiXin2,HUANG XianHui1()   

  1. 1 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642
    2 Shanghai Animal Disease Control Center, Shanghai 201103
  • Received:2018-11-12 Accepted:2019-03-29 Online:2019-08-16 Published:2019-08-21
  • Contact: XianHui HUANG E-mail:xhhuang@scau.edu.cn

RichHTML

12

PDF

2337

Abstract:

【Objective】The study was carried out to investigate the antibacterial activity in vitro and protection of tildipirosin injection against artificially infected Haemophilus Paracoides in piglets. 【Method】Minimal inhibitory concentration (MIC) of Tildipirosin injection against Haemophilus paracoides, Actinobacillus pleuropneumonia, Pasteurella multiflora, and Bronchial septicemic wave bacillus were determined by two-fold dilution method in vitro. In the protective effect of tildipirosin injection against Haemophilus paracoides in piglets, 0.5 mL·kg -1bw suspension of Haemophilus paracoides with a bacterial volume of 1 10 10 CFU·mL -1 was selected as the challenge dose for intraperitoneal injection to replicate the pathological model. All the therapeutic groups of pigs were medicated via intramuscular injection in single dose with tildipirosin injection (2, 4, 8 mg·kg -1bw), tulathromycin (2.5 mg·kg -1bw). In the process of isolating and identifying dead pig pathogens, isolated and purified Haemophilus paracoides colonies were selected for genomic DNA extraction. A pair of specific primers were designed for the 16s RNA sequence of Haemophilus paracoides, and the base sequence length of the target DNA fragment was tested after PCR amplification.【Result】The results of the antibacterial activity in vitro showed that MIC of Haemophilus paracoides, Septicopharynx, Actinobacillus pleuropneumoniae and Pasteurella multocida for tildipirosin injection was 0.06-8, 0.06-8, 0.25-1, and 2-32 μg·mL -1, respectively, which indicated the effect of Tildipirosin injection against Haemophilus paracoides and Septicopharynx was stronger than Actinobacillus pleuropneumoniae and Pasteurella multocida. PCR amplification results of the DNA target fragment showed that the length of the PCR amplification target fragment was consistent with the predicted band, and the specific fragment length was about 820bp, which indicated that all the dead pigs died of Haemophilus paracoides infection. The result of protective effect indicated that, in tildipirosin injection groups (2, 4, 8 mg·kg -1bw), the average gain of weight was (2.5±0.2), (2.9±0.2), (2.9±0.3) kg, respectively; the mortality rate were 40%, 0 and 0, respectively; the effective rate was 40%, 100% and 100%, respectively; the cure rate was 40%, 100% and 100%, respectively. In tulathromycin injection groups (2.5 mg·kg -1bw), the average gain of weight was (3.0±0.2) kg; the mortality rate were 10%; the effective rate was 90%; the cure rate was 80%. In infective control group, the average gain of weight was (2.1±0.1) kg; the mortality rate were 70%. The results of in vitro treatment showed that there was no significant difference between the high- and medium-dose group of tildipirosin and the tulathromycin group (P>0.05), which could alleviate the clinical symptoms rapidly and had significant therapeutic effects. The therapeutic effect of tildipirosin low-dose group was comparable to the non-administered group, and there was no significant difference (P>0.05). 【Conclusion】Through the above results, the product was recommended to be administered at a dose of 4 mg·kg -1bw, which could effectively treat respiratory diseases in pigs caused by Haemophilus Parasuis infection.

Key words: tildipirosin injection, MIC, Haemophilus Paracoides, piglet

Table 1

The groups and treatment of animals"

组别
Groups		 数量（头）
Numbers (Head)		 体重
Weights (kg)		 剂量
Dosage (mg·kg-1bw)		 给药方案
Drug regimen
健康对照组
Healthy control group		 10 12.5±0.6 — 不感染,不给药
No infection, No administration
泰地罗新注射液高剂量组
High dose group of Tildipirosin injection		 10 12.9±0.9 8.0 感染,肌注注射
Infection,im
泰地罗新注射液中剂量组
Middle dose group of Tildipirosin injection		 10 12.9±1.1 4.0 感染,肌注注射
Infection,im
泰地罗新注射液低剂量组
Low dose group of Tildipirosin injection		 10 12.7±0.9 2.0 感染,肌注注射
Infection,im
泰拉霉素注射液
Tulathromycin injection		 10 13.1±0.5 2.5 感染,肌注注射
Infection,im
感染对照组
Infective control group		 10 12.5±0.6 — 感染,不给药
Infection, No administration

Table 2

PCR reaction system"

体系组分
System components		 用量
The dosage (μL)
灭菌超纯水 Sterilized ultra-pure water 12.6
10×PCR buffer 2
dNTP（2.5 mmol·L-1） 1.6
上游引物 Forward primer 0.8
下游引物 Reverse primer
模板DNA（Template DNA）		 0.8
2
rTag DNA酶 rTag DNA enzyme, 5 U·μL-1 0.2

Table 3

The results of MIC(μg/mL) of tildipirosin against four stains"

菌种
Bacterial strain		 MIC MIC50 MIC90
胸膜肺炎放线杆菌（39株）Actinobacillus pleuropneumonia（39 strains） 2-32 4 16
多杀性巴氏杆菌（25株）Pasteurella multiflora（25 strains） 0.25-1 0.5 1
支气管败血波氏杆菌（10株）Bronchial septicemic wave bacillus（10 strains） 0.06-8 2 8
副猪嗜血杆菌（74株）Haemophilus Paracoides（74 strains） 0.06-8 0.5 2

Table 4

Poison attack dose and results of 50 healthy pigs"

菌株
Bacterial strain		 日龄接种
Inoculate days		 活菌量
Living bacterium
quantity (CFU/mL)		 接种剂量
Inoculation dosage (mL·kg-1）		 数量（头）
Number
(Head)		 攻毒结果 Poison attack results
发病数量（头）
Morbidity（Head）		 死亡数量（头）
Mortality（Head）
13R 7-8周龄
7-8 weeks		 1×1010 0.3 10 5 1
1×1010 0.5 10 10 7
1×1010 0.8 10 10 10
1×1010 1 10 10 10
TSB培养基
TSB medium		 7-8周龄
7-8 weeks		 1×1010 1mL 10 0 0

Fig. 1

Temperature of each experimental group after administration"

Fig. 2

Clinical symptom observation results of piglets"

Table 5

Mean temperature and standard deviation of each experimental group after administration"

时间
Time (h)		 健康对照组
Healthy control
group		 泰地罗新注射液
高剂量组
High dose group of Tildipirosin injection		 泰地罗新注射液
中剂量组
Middle dose group of Tildipirosin injection		 泰地罗新注射液
低剂量组
Low dose group of Tildipirosin injection		 泰拉霉素注射液
Tulathromycin injection		 感染对照组
Infective control
group
0 39.2±0.18 39.4±0.19 39.1±0.22 39.2±0.20 38.9±0.22 39.3±0.31
1 39.1±0.19 40.2±0.18 40.6±0.23 40.4±0.22 40.2±0.18 40.5±0.29
3 39.2±0.22 41.2±0.21 41±0.19 41.1±0.21 41.2±0.21 41±0.22
4 38.6±0.21 40.9±0.20 40.8±0.17 41.3±0.22 41.1±0.19 41.8±0.28
6 39.3±0.20 40.4±0.19 40.4±0.16 40.7±0.24 40.7±0.23 41.2±0.17
8 39.1±0.17 40.1±0.23 40±0.21 40.5±0.18 40.3±0.21 40.8±0.19
12 38.9±0.20 39.5±0.18 39.5±0.22 40.2±0.19 39.6±0.18 40.9±0.24
24 39±0.19 39.3±0.23 39.5±0.18 40.2±0.22 39.2±0.19 40.6±0.22
36 39.2±0.23 39.4±0.25 39.1±0.19 39.5±0.22 39.4±0.27 40.5±0.28
48 38.8±0.16 39.2±0.21 39.3±0.20 39.5±0.24 39.1±0.26 40.7±0.26
60 39.1±0.21 39.2±0.20 39±0.20 39.4±0.22 38.9±0.29 40.8±0.21
72 38.9±0.22 38.9±0.17 39.4±0.22 39.3±0.22 39.2±0.19 40.6±0.27
84 39.2±0.18 39.3±0.22 39.4±0.25 38.9±0.21 39±0.18 40.5±0.30
96 39.1±0.19 38.8±0.20 38.9±0.21 39.2±0.22 39.3±0.21 40.4±0.22
108 39.3±0.20 39.1±0.24 39.2±0.19 39.1±0.19 38.9±0.21 40.5±0.22
120 38.7±0.22 39.1±0.22 39±0.17 39.4±0.22 39.2±0.22 40.4±0.24
132 39.2±0.18 39.2±0.19 39.2±0.20 38.8±0.24 39.4±0.19 40.3±0.25
144 39.1±0.21 39.2±0.21 39.3±0.20 39.2±0.21 39.1±0.21 40.4±0.21
156 39.4±0.21 39.4±0.25 39.2±0.18 39±0.22 39.2±0.18 40.3±0.24

Table 6

Weight change in each dose group during the trial ($\bar{X}$±S.D)"

组别
Groups		 试验前体重
Pretrial weight (kg)		 试验后体重
Posttest weigh (kg)		 增重
Weight increment (kg)
健康对照组 Healthy control group 12.5±0.6 15.5±0.7 3.0±0.2a
泰地罗新高剂量组 High dose group of Tildipirosin injection 12.9±0.9 15.8±1.2 2.9±0.3a
泰地罗新中剂量组 Middle dose group of Tildipirosin injection 12.9±1.1 15.7±1.2 2.9±0.2a
泰地罗新低剂量组 Low dose group of Tildipirosin injection 12.7±0.9 15.2±0.9 2.5±0.2b
泰拉霉素注射液 Tulathromycin injection 13.1±0.5 16.1±0.6 3.0±0.2a
感染对照组 Infective control group 12.5±0.6 14.6±0.7 2.1±0.1c

Fig. 3

Observation results of ocular pathological changes"

Fig. 4

Observation of pathogen isolation and culture"

Fig. 5

PCR results of 16S rRNA from Haemophilus parthenosus"

Table 7

The therapy of Tildipirosin injection against Haemophilus Paracoides in pigs (Effective rate)"

编号
No.		 组别
Groups		 头数
Head		 死亡率
Mortality (%)		 有效率
Efficient (%)		 治愈率
Cure rate (%)		 与第5组 比较
（χ2检验）
Compare with group 5 (χ2 test)		 与第4组 比较
（χ2检验）
Compare with group 4 (χ2 test)		 与第3组
比较
（χ2检验）
Compare with group 3 (χ2 test)		 与第2组 比较
（χ2检验）
Compare with group 2 (χ2 test)
1 泰地罗新高剂量组
High dose group of Tildipirosin injection		 10 0（0/10） 100（10/10） 100（10/10） 20 1.053 8.571 1.053
2 泰地罗新中剂量组
Middle dose group of Tildipirosin injection		 10 0（0/10） 100（9/10） 90（9/10） 16.36 0 5.495 -
3 泰地罗新低剂量组
Low dose group of Tildipirosin injection		 10 40（4/10） 40（4/10） 30（3/10） 5 5.495 - -
4 泰拉霉素注射液
Tulathromycin injection		 10 10（1/10） 90（9/10） 80（8/10） 16.364 - - -
5 感染对照组
Infective control group		 10 70（7/10） - - - - - -
6 健康对照组
Healthy control group		 10 - - - - - - -

Table 8

The therapy of Tildipirosin injection against Haemophilus Paracoides in pigs (Cure rate)"

编号
No.		 组别
Groups		 头数
Head		 死亡率
Mortality (%)		 有效率
Efficient (%)		 治愈率
Cure rate (%)		 与第5组 比较
（χ2检验）
Compare with group 5 (χ2 test)		 与第4组 比较
（χ2检验）
Compare with group 4 (χ2 test)		 与第3组
比较
（χ2检验）
Compare with group 3 (χ2 test)		 与第2组 比较
（χ2检验）
Compare with group 2 (χ2 test)
1 泰地罗新高剂量组
High dose group of Tildipirosin injection		 10 0（0/10） 100（10/10） 100（10/10） 20 2.222 10.769 1.053
2 泰地罗新中剂量组
Middle dose group of Tildipirosin injection		 10 0（0/10） 100（9/10） 90（9/10） 16.364 0.392 7.5 -
3 泰地罗新低剂量组
Low dose group of Tildipirosin injection		 10 40（4/10） 40（4/10） 30（3/10） 3.529 5.051 - -
4 泰拉霉素注射液
Tulathromycin injection		 10 10（1/10） 90（9/10） 80（8/10） 13.333 - - -
5 感染对照组
Infective control group		 10 70（7/10） - - - - - -
6 健康对照组
Healthy control group		 10 - - - - - - -

Table 9

The therapy of Tildipirosin injection against Haemophilus Paracoides in pigs (Mortality rate)"

编号
No.		 组别
Groups		 头数
Head		 死亡率
Mortality (%)		 有效率
Efficient (%)		 治愈率
Cure rate (%)		 与第5组 比较
（χ2检验）
Compare with group 5 (χ2 test)		 与第4组 比较
（χ2检验）
Compare with group 4 (χ2 test)		 与第3组
比较
（χ2检验）
Compare with group 3 (χ2 test)		 与第2组 比较
（χ2检验）
Compare with group 2 (χ2 test)
1 泰地罗新高剂量组
High dose group of Tildipirosin injection		 10 0（0/10） 100（10/10） 100（10/10） 10.769 1.053 5 /
2 泰地罗新中剂量组
Middle dose group of Tildipirosin injection		 10 0（0/10） 100（10/10） 90（9/10） 10.769 1.053 5 -
3 泰地罗新低剂量组
Low dose group of Tildipirosin injection		 10 40（4/10） 40（4/10） 30（3/10） 1.818 2.400 - -
4 泰拉霉素注射液
Tulathromycin injection		 10 10（1/10） 90（9/10） 80（8/10） 7.500 - - -
5 感染对照组
Infective control group		 10 70（7/10） - - - - - -
6 健康对照组
Healthy control group		 10 - - - - - - -
[1] 李艳华, 蔡雪辉, 刘永刚, 姜成刚, 王洪峰, 柴文君 . 合理选择抗菌药治疗猪细菌性呼吸道疾病的原则. 中国畜牧兽医, 2004(11):47-49.
LI Y H, CAI X H, LIU Y G, JIANG C G, WANG H F, CHAI W J . Principles of rational selection of antimicrobial agents for the treatment of porcine bacterial respiratory diseases. China Animal Husbandry and Veterinary Medicine, 2004(11):47-49. (in Chinese)
[2] 霍望, 李春生, 韩维丽 . 猪呼吸道疾病的综合防制措施. 现代畜牧兽医, 2007(12):33-34.
HUO W, LI C S, HAN W L . Comprehensive control measures of respiratory diseases in pigs. Modern Journal of Animal Husbandry and Veterinary Medicine, 2007(12):33-34. (in Chinese)
[3] BROCKMEIER S L, LOVING C L, MULLINS M A, REGISTER K B, NICHOLSON T L, WISEMAN B S, BAKER R B, KEHRLI M E . Virulence, transmission, and heterologous protection of four isolates of Haemophilus parasuis. Clinical and Vaccine Immunology, 2013, 20(9):1466-1472.
[4] BROCKMEIER S L, REGISTER K B, KUEHN J S, NICHOLSON T L, LOVING C L, BAYLES D O, SHORE S M, PHILLIPS G J . Virulence and draft genome sequence overview of multiple strains of the swine pathogen Haemophilus parasuis. PLoS One, 2014,9:e1037878.
[5] BROCKMEIER S L, MARTIN DE LA FUENTE A J, GUTIERREZ MARTIN C B, PEREZ MARTINEZ C, GARCIA IGLESIAS M J, TEJERINA F, RODRIGUEZ FERRI E R . Effect of different vaccine formulations on the development of Glasser's disease induced in pigs by experimental Haemophilus parasuis infection. Journal of Comparative Pathology, 2009, 140(2-3):169-176.
[6] HU M, ZHANG Y, XIE F, LI G, LI J, SI W, LIU S, HU S, ZHANG Z, SHEN N, WANG C . Protection of piglets by a Haemophilus parasuis ghost vaccine against homologous challenge. Clinical and Vaccine Immunology, 2013,20(6):795-802.
[7] MURTAUGH M P . Advances in swine immunology help move vaccine technology forward. Veterinary Immunology and Immunopathology, 2014,159(3-4SI):202-207.
[8] ZHANG B, YU Y, ZENG Z, REN Y, YUE H . Deletion of the rfaE gene in Haemophilus parasuis SC096 strain attenuates serum resistance, adhesion and invasion. Microbial Pathogenesis, 2014,74:33-37.
[9] KIELSTEIN P , RAPP-GABRIELSON V J. Designation of 15 serovars of Haemophilus parasuis on the basis of immunodiffusion using heat-stable antigen extracts. Journal of Clinical Microbiology, 1992,30(4):862-865.
[10] RAPP-GABRIELSON V J, GABRIELSON D A, SCHAMBER G J . Comparative virulence of Haemophilus parasuis serovars 1 to 7 in guinea pigs. American Journal of Veterinary Research, 1992,53(6):987-994.
[11] NIELSEN R . Pathogenicity and immunity studies of Haemophilus parasuis serotypes. Acta Veterinaria Scandinavica, 1993,34(2):193-198.
[12] MACEDO N, ROVIRA A, TORREMORELL M . Haemophilus parasuis: infection, immunity and enrofloxacin. Veterinary Research, 2015,46:128.
[13] HUANG X, LI Y, FU Y, JI Y, LIAN K, ZHENG H, WEI J, CAI X, ZHU Q . Cross-protective efficacy of recombinant transferrin-binding protein A of Haemophilus parasuis in guinea pigs. Clinical and Vaccine Immunology, 2013,20(6):912-919.
[14] YUAN F, FU S, HU J, LI J, CHANG H, HU L, CHEN H, TIAN Y, BEI W . Evaluation of recombinant proteins of Haemophilus parasuis strain SH0165 as vaccine candidates in a mouse model. Research in Veterinary Science, 2012,93(1):51-56.
[15] VANNUFFEL P, COCITO C . Mechanism of action of streptogramins and macrolides. Drugs, 1996,51(Suppl. 1):20-30.
[16] POEHLSGAARD J, ANDERSEN N M, WARRASS R, DOUTHWAITE S . Visualizing the 16-membered ring macrolides tildipirosin and tilmicosin bound to their ribosomal site. ACS Chemical Biology, 2012,7(8):1351-1355.
[17] EMA. Committee for Medicinal Products for Veterinary Use (EMA/CVMP /91406/2011) [DB/OL][EB/OL].[0809]. Available at: . http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion__Initial_authorisation/veterinary/002009/WC500103295.pdf
[18] 李伟岭, 杨芳, 于振梅, 岳永波 . 泰地罗新研究进展. 中国兽药杂志, 2012(10):50-53.
LI W L, YANG F, YU Z M, YUE Y B . Progress of the studies on tildipirosin. Chinese Journal of Veterinary Drug, 2012(10):50-53. (in Chinese)
[19] D. E. AMRINE B J W R . Pulmonary lesions and clinical disease response to Mannheimia haemolytica challenge 10 days following administration of tildipirosin or tulathromycin. Journal of Animal Science, 2014,92(1):311-319.
[20] LEI Z, LIU Q, YANG B, AHMED S, CAO J, HE Q . The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis. Oncotarget, 2018,9(2).
[21] 廖远军 . 泰地罗新注射液在猪体内的药代动力学研究[D]. 长春:吉林大学, 2015.
LIAO Y J . Studies on Pharmacokinetics of Tildipirosin Injection in Pigs[D]. Changchun:Jilin University, 2015. (in Chinese)
[22] 刘伟 . 泰地罗新肌注后在猪体内的残留消除研究[D]. 广州:华南农业大学, 2016.
LIU W . Study on the Residue Elimination of Tildipirosin in Pigs[D]. Guangzhou:South China Agricultural University, 2016. (in Chinese)
[23] 刘建奎, 杨小燕, 魏春华, 李晓华, 戴爱玲, 杨兰秀 . 副猪嗜血杆菌PCR检测方法的建立与初步应用. 湖北农业科学, 2012(17):3794-3796.
LIU J K, YANG X Y, WEI C H, LI X H, DAI A L, YANG L X . Establishment and preliminary application of PCR assay to detectHaemophilus parasuis. Hubei Agricultural Sciences, 2012(17):3794-3796. (in Chinese)
[24] 周煜 . 16S rRNA序列分析法在医学微生物鉴定中的应用. 生物技术通讯, 1999(04):297-305.
ZHOU Y . Application of 16S ribosomal RNA approach for the identification of medical microbe. Letters in Biotechnology, 1999(04):297-305. (in Chinese)
[25] LEI Z, LIU Q, YANG S, YANG B, KHALIQ H, LI K, AHMED S, SAJID A, ZHANG B, CHEN P, QIU Y, CAO J, HE Q . PK-PD integration modeling and cutoff value of florfenicol against Streptococcus suis in pigs. Front Pharmacology, 2018,9:2.
[26] ANDERSEN N M, POEHLSGAARD J, WARRASS R, DOUTHWAITE S . Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides. Antimicrobial Agents and Chemotherapy, 2012,56(11):6033-6036.
[27] EMA. CVMP assessment report Zuprevo (EMA/V/002009) [EB/OL]. [0810]. available at: . http://www.ema.europa.eu/ema/index.jspcurl= pages/medicines/veterinary/medicines/002009/vet_med_000242.jsp&mid=pages/medicines/medicines. jsp&mid=WC0b01ac058001fa1c
[28] OLIVEIRA S, GALINA L, PIJOAN C . Development of a PCR test to diagnose Haemophilus parasuis infections. Journal of Veterinary Diagnostic Investigation, 2001,13(6):495-501.
[29] VAHLE J L, HAYNES J S, ANDREWS J J . Interaction of Haemophilus parasuis with nasal and tracheal mucosa following intranasal inoculation of cesarean derived colostrum deprived (CDCD) swine. Canadian Journal of Veterinary Research, 1997,61(3):200-206.
[30] LI X, ZHAO G, QIU L, DAI A, WU W, YANG X . Protective efficacy of an inactive vaccine based on the LY02 isolate against acute Haemophilus parasuis infection in piglets. BioMed Research International, 2015,2015:1-8.
[31] OLIVEIRA S, GALINA L, BLANCO I, Canals A, Pijoan C . Naturally-farrowed, artificially-reared pigs as an alternative model for experimental infection by Haemophilus parasuis. Canadian Journal of Veterinary Research, 2003,67(2):146-150.
[32] 赵国振, 李晓华, 戴爱玲, 吴王伟, 黄雪招, 杨小燕 . 血清5型副猪嗜血杆菌的仔猪致病性研究. 龙岩学院学报, 2015,33(05):79-84.
ZHAO G Z, LI X H, DAI A L, WU W W, HUANG X Z, YANG X Y . Study on the pathogenicity of Haemophilus parathophilus of serum type 5 in piglets. Journal of Long Yang University, 2015,33(05):79-84. (in Chinese)
[33] 黄金虎, 刘民星, 商可心, 王丽平 . 46株猪链球菌对大环内酯类抗生素的耐药性及PFGE分型. 南京农业大学学报, 2013(04):105-110.
HUANG J H, LIU M X, SHANG K X, WANG L P . Macrolide resistance and pulsed-field gel electrophoresis typing of 46Streptococcus suis isolates. Journal of Nanjing Agricultural University, 2013(04):105-110. (in Chinese)
[34] WATTS J L, SWEENEY M T . Antimicrobial resistance in bovine respiratory disease pathogens: measures, trends, and impact on efficacy. Veterinary Clinics of North America: Food Animal Practice, 2010,26(1):79-88.
[35] 亢继俊, 王丽霞, 曾振灵 . 动物专用大环内酯类新药——泰拉霉素. 广东畜牧兽医科技, 2010(02):7-10.
HANG J J, WANG L X, ZENG Z L . A new macrolide antibiotic tulathromycin for animals. Guangdong Journal of Animal and Veterinary Science, 2010(02):7-10. (in Chinese)
[36] EMA. Committee for medicinal products for veterinary use[EB/OL]. [0809]. Available at: . http://www.ema.europa.eu/docs/en_GB/ document_ library/Maximum_Residue_Limits__Report/2010/10/WC500097539.pdf
[37] 闫超群, 黎健业, 张申, 谢顺, 胡浪, 顾欣, 曹莹, 黄士新, 黄显会 . 泰地罗新注射液在猪体内的药动学及生物利用度研究. 中国农业科学, 2018(19):3807-3814.
YAN C C, LI J Y, ZHANG S, XIE S, HU L, GU X, CAO Y, HUANG S X, HUANG X H . Pharmacokinetics and bioavailability of tildipirosin solution in pigs. Scientia Agricultura Sinica, 2018(19):3807-3814. (in Chinese)
[38] ROSE M, MENGE M, BOHLAND C, ZSCHIESCHE E, WILHELM C, KILP S, METZ W, ALLAN M, ROPKE R, NURNBERGER M . Pharmacokinetics of tildipirosin in porcine plasma, lung tissue, and bronchial fluid and effects of test conditions on in vitro activity against reference strains and field isolates of Actinobacillus pleuropneumoniae. Journal of Veterinary Pharmacology and Therapeutics, 2013,36(2):140-153.
[1] CUI JieHao, ZHANG Meng, WANG Qin, YU JiaYan, LIN Kun, LI ShangZe, LAN Heng, GENG YanQiu, ZHANG Qiang, GUO LiYing, SHAO XiWen. Evaluation of Lodging Resistance and Its Physiological Mechanisms in Japonica Rice Resources [J]. Scientia Agricultura Sinica, 2026, 59(7): 1420-1438.
[2] WANG YaFei, YAN Peng, XUE JinTao, DONG XueRui, MENG FanQi, GUO LiNa, LUO Yi, ZHANG Juan, DONG ZhiQiang, LU Lin. Effects of Ethephon-Glycine Betaine-Salicylic Acid Mixture on Root System Architecture, Physiological Function and Yield of Maize Under Heat Stress [J]. Scientia Agricultura Sinica, 2026, 59(7): 1439-1455.
[3] XU YangHaoJun, CHEN LiMing, YANG ShiQi, TANG YiFan, TAN XueMing, ZENG YongJun, PAN XiaoHua, ZENG YanHua. Effects of Long-Term Different Straw Returning Methods on Soil Organic Carbon, Nutrients and Aggregate Formation in Different Soil Layers of Double Cropping Rice Field [J]. Scientia Agricultura Sinica, 2026, 59(7): 1492-1506.
[4] YE MeJin, WU Lei, MD NAHIBUZZAMAN Lohani, YIN Li, HU XinRong, LIU YaXi, JIANG YunFeng, CHEN GuoYue, PU ZhiEn, LI Yang, LI Ting, ZOU YaYa, WU JiaYi, MA Jian. Genome-Wide Association Study-Based Identification of Loci Controlling Mature Embryo Size in Chinese Wheat Landraces and Their Genetic Effects Analysis [J]. Scientia Agricultura Sinica, 2026, 59(6): 1157-1171.
[5] DU MengYuan, HOU YanHong, LIU Di, CHEN Li, FAN ZhiYe, WANG WenHao, SHEN HaiLong, WANG CanGuan, LI ShiMin, HUANG JianRong, CHEN Qi. Analysis of Population Dynamics and Migration Status of Harmonia axyridis Under Searchlight Trap and Ground Light Trap [J]. Scientia Agricultura Sinica, 2026, 59(6): 1231-1243.
[6] LI YongJuan, ZHANG YueTong, WANG YiBo, ZHAO ChangJiang, SONG Jie, CHEN XueLi, YAO Qin. Effects of Biochar Application on the Abundance and Community Composition of Nitrogen-Fixing Microbial nifH Gene in Soybean Rotation and Continuous Cropping Systems [J]. Scientia Agricultura Sinica, 2026, 59(6): 1272-1285.
[7] WEI YuanHui, YU YiHui, LI ZiJun, DING WenJie, TU WenLong, MAO YanLing. Effects of Long-Term Fertilization on Soil Organic Carbon Structure and Carbon-Fixing Bacterial Community Structure in Yellow-Mud Paddy Soil [J]. Scientia Agricultura Sinica, 2026, 59(5): 1020-1033.
[8] YUE LiXin, WANG QingHua, WANG ZhenBao, NIMAQIONGJI, LIU ZeZhou, KONG SuPing, ZHANG LiFeng, GAO LiMin. Widely Targeted Metabolomics-Based Analysis of the Differences in Tibetan Bunching Onion and Chive on Nutritional Quality and Flavonoid Metabolites [J]. Scientia Agricultura Sinica, 2026, 59(5): 1070-1086.
[9] WANG ShaoHua, FAN QiuLi, YANG JinChang, SUN YuJie, YU Niu, JIANG ShouQun. Effects of Different Levels of Mytilaria laosensis Leaves Feeding on Growth Performance, Immune Function, Antioxidant Capacity, Carcass Quality and Meat Quality of Yellow-Feathered Chickens [J]. Scientia Agricultura Sinica, 2026, 59(5): 1111-1127.
[10] WEN YuBin, BAI ShanShan, CAI ZeJiang, SUN Nan, XU MingGang. Effects of Organic Materials on Soil Microbial Biomass and Its Acidity Regulation Mechanism [J]. Scientia Agricultura Sinica, 2026, 59(4): 834-849.
[11] XIAN QingLin, XIAO JianKe, GAO AQing, GAO LiChuang, LIU Yang. Effects of Planting Patterns Combined with Soil Moisture Measurement and Supplementary Irrigation on the Yield and Water Use Efficiency of Winter Wheat [J]. Scientia Agricultura Sinica, 2026, 59(3): 589-601.
[12] PEI HongXia, WANG LuYao, JIANG YaPing, LI ShengMei, GAO JingXia. Identification of Nuclear Male Sterility Genes in Pepper Based on BSA-Seq and Proteomics [J]. Scientia Agricultura Sinica, 2026, 59(3): 637-654.
[13] LI Yun, ZHANG Fan, ZHOU YongQi, QIAO ZhiHao, LIU YanLi. Analysis of Body Size Traits During Growth and Development and Comparison of Meat Quality and Flavor Between 13 and 16 Weeks Lueyang Black-Bone Chickens [J]. Scientia Agricultura Sinica, 2026, 59(2): 427-440.
[14] GUO HuiTing, SUN YanWen, NIU YiHeng, LI YaPeng, LI JianHua, XU MingGang. Fertilization Significantly Changed Soil Bacterial Diversity and Dominant Microbial Community in Croplands of Northern China—Meta Analysis [J]. Scientia Agricultura Sinica, 2026, 59(1): 114-128.
[15] LI Xue, XU Yan, MAO XueFei. Agroelementomics: Concept, Progress and Perspective in Analytical Techniques [J]. Scientia Agricultura Sinica, 2026, 59(1): 190-204.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
京ICP备09089781号-30
Copyright 2018 © Editorial office of Scientia Agricultura Sinica
Tel: 86-010-82106279    E-mail: zgnykx@mail.caas.net.cn
Supported by Beijing Magtech Co.Ltd