Study On Safety And Clinical Efficacy Of Gamithromycin Injection On Bacterial Swine Respiratory Disease

Objective: Swine respiratory disease is a kind of disease which often causes serious harm to the pig industry.As a robust pig products consumers and supplier,China faces pressing needs to develop and to produce new veterinary drugs for swine respiratory diseases.Gamithromycin is a second-generation macrolide semi-synthetic veterinary antibiotic that can be rapidly distributed to the target organ lung and has good antibacterial activity to some respiratory pathogens,such as Actinobacillus pleuropneumoniae,Haemophilus parasuis and Pasteurella multocida.Gamithromycin has been approved by Food and Drug Administration and European Medicines Agency for the treatment of swine respiratory diseases caused by the above pathogens.China has not yet approved gamithromycin for veterinary clinics.In this study,t hrough safety test and phase II/III clinical trials,we evaluated the safety and efficacy of gamithromycin injection developed by Baoding Jizhong Biotechnology Co.,Ltd.on target animal pigs.The aim of this study is to provide a theoretical basis for the application of new veterinary drugs for gamithromycin injection.Methods:(1)According to "VICH Overview of Guiding Principles for Safety Research of Veterinary Drug Targets” issued by Ministry of Agriculture and Rural Affairs of China,twenty-four healthy binary hybrid pigs of 70-days old were randomly divided into 4 groups,and on day0,day5,and day10,the four groups were intramuscularly administrated a recommended dose of 6 mg/kg(BW)gamithromycin injection by 1,3,and 5 times.The pigs were weight ed,clinical results observed and blood routine physiological indexes and blood biochemical indexes measured.On day15,the pigs were butchered and heart,liver,spleen and other tissues collected.Pathological sections were prepared for histological observation.(2)The minimum inhibitory concentrations(MIC)of gamithromycin on Actinobacillus pleuropneumoniae,Haemophilus parasuis,Pasteurella multocida and Streptococcus suis isolated from swine nasal swabs were measured through in vitro susceptibility test.(3)According to "Guidelines for Phase II/III Clinical Efficacy Evaluation Tests” issued by Ministry of Agriculture and Rural Affairs of China,120 pigs with naturally infected respiratory diseases were screened,which were randomly divided into 3 mg/k g,6 mg/kg,12 mg/kg gamithromycin treatment group and 2.5 mg/kg tulathromycin control treatment group.The therapeutic effects of different doses of gamithromycin injection were evaluated by clinical symptoms score.(4)According to "Guidelines for Phase II/III Clinical Efficacy Evaluation Tests” issued by Ministry of Agriculture and Rural Affairs of China 120 pigs with naturally infected respiratory diseases were screened,which were randomly divided into 6mg/kg gamithromycin treatment group and 2.5 mg/kg tulathromycin control treatment group.The therapeutic effect of therecommended dose of gamithromycin injection was evaluated by the clinical symptoms score.Results:(1)In the safety test,the groups of 1,3 and 5 times recommended doses of the gamithromycin injection showed no significant difference compared with the control group(P>0.05).(2)In the in vitro susceptibility test,the MIC90 s of gamithromycin on Actinobacillus pleuropneumoniae,Haemophilus parasuis,Pasteurella multocida and Streptococcus suis were 2 ?g/m L,0.5 ?g/m L,4 ?g/m L and 8 ?g/m L respectively.(3)In the phase II clinical trial,the cure rates of the 3 mg/kg,6 mg/kg and 12 mg/kg gamithromycin treatment group and the 2.5 mg/kg tulathromycin treatment group were 63.33%,80.00%,80.00%,a nd 80.00% respectively.There was no significant difference between 6 mg/kg,12 mg/kg gamithromycin treatment group and 2.5 mg/kg tulathromycin treatment group in the treatment of bacterial swine respiratory disease(P>0.05).(4)In the phase III clinical trial,the cure rates of 6 mg/kg gamithromycin treatment group and 2.5 mg/kg tulathromycin treatment group were 80.00% and 81.67% respectively.There was no significant difference between 6 mg/kg gamithromycin treatment group and 2.5 mg/kg tulathromycin treatment group in the treatment of bacterial swine respiratory disease(P>0.05).Conclusion: Gamithromycin injection developed by Baoding Yuzhong Biotechnology Co.,Ltd.is effective for swine respiratory diseases caused by Actinobacillus pleuropneumoniae,Haemophilus parasuis,Pasteurella multocida and Streptococcus suis.It has no obvious adverse reactions to swine.The recommended treatment dose is 6 mg/kg BW through one intramuscular injection.