| Bacitracin methylene disalicylate(BMD)has strong antimicrobial activity against Gram-positive bacteria and Clostridium perfringens.The US FDA-approved indications for BMD include increasing daily weight gain and feed replenishment,increasing egg production in laying hens,preventing chicken necrotic enteritis,treating vaginal infectious enteritis,preventing ulcerative enteritis and swine dysentery.In the European Union,this drug is also recommended for the treatment of rabbit necrotic enteritis caused by Clostridium perfringens.In China,currently approved indications for BMD-containing preparations include treatment of chicken necrotic enteritis and S.aureus infections caused by Clostridium perfringens,and for duck growth.To objectively evaluate the efficacy and safety of the drug against necrotic enteritis caused by Clostridium perfringens in rabbits,the rabbit necrotic enteritis model induced by artificial infection and clinical cases were performed.This study provides a basis for the efficacy and safety evaluation of BMD soluble powder in preventing and treating necrotic enteritis caused by Clostridium perfringens in rabbits.1.Phase ? clinical pharmacodynamic study of BMD soluble powder on rabbit necrotic enteritis.The rabbit necrotic enteritis model was replicated by artificial infection of C7ostridium per.fringens to evaluate the effectiveness of BMD soluble powder in the treatment of rabbit necrotic enteritis and determine the optimal effective dose.150 healthy rabbits of 35-day-old were randomly divided into 5 groups,30 per group.The test drugs were divided into three dose groups,which were administered with 3 mg/kg·bw/d,6 mg/kg bw/d and 12 mg/kg bw/d for 10 days,respectively;another group of infected control group and blank control group were set up.Inefficiency and cure rate were set as main pharmacodynamic evaluation indicators.The results showed that the cure rates of the low,medium and high dose groups were 56.7%,76.7%and 90%,respectively,which were significant higher than the infected control group.However,significant differences between the low-dose groups and medium/high dose group was observed.The results showed that BMD soluble powder at a dose of 6 mg/kg bw/d for 10 days had a good therapeutic effect on rabbit necrotic enteritis.2.Phase ? clinical pharmacodynamic study of BMD soluble powder on rabbit necrotic enteritis.On the basis of the phase ? clinical dose screening test,the rabbit field of Clostridium perfringens necrotic enteritis in rabbits was selected to further verify the control effect of BMD soluble powder on the disease at the recommended dose,and the possible adverse reactions during the drug administration was recorded.A total of 240 clinically infected rabbits were randomly divided into 2 groups,120 in each group,which were divided into infection control group and test drug group.The recommended dosage of 6 mg/kg bw/d was mixed for 10 days.Inefficiency and cure rate were performed as main pharmacodynamic evaluation indicators.The results showed that no abnormal manifestations and signs were found in all experimental rabbits except the symptoms associated with necrotizing enteritis.And the cure rate of the test group was 87.5%,and the self-healing rate of the infected control group was 44.2%.There was a significant difference between the two groups.The results also suggested that BMD soluble powder mixed with 6 mg/kg·bw/d for 10 days was safe and effective in the treatment of rabbit necrotizing enteritis caused by Clostridium perfringens.3.Safety Test of BMD Soluble Powder in Target Animal RabbitsThirty-two healthy adult New Zealand rabbits were randomly divided into 4 groups,8 in each group(female and male half).The safety of target animals was studied by using multiple dose levels,groups were given BMD Soluble Powder with water at dosage of recommended dosage(6 mg/kg bw/d),3 times of recommended dosage(18 mg/kg·bw/d)or 5 times of recommended dosage(30 mg/kg-bw/d)for 21 d continuously.During the course of treatment,the safety of test drug in target animals was assessed by observing changes in general clinical manifestations,body weight and food intake,detection of hematology and blood biochemical indicators,and gross and histopathological examination.The results showed that all the tested animals survived during the test,and the clinical manifestations of the control group and the test drug group were normal.There were no obvious pathological changes in the pathological anatomy of the main organs.Compared with the control group,the recommended dose group had a positive effect on the growth performance of rabbits.There were no significant differences between the experimental groups in blood physiological and biochemical parameters.After the necropsy,ino significant lesions were observed in the gross and microscopic pathology of the main organs of the rabbits in the control group and the 5-fold dose group.These results demonstrated that it was safe for rabbits to use BMD soluble powder at the recommended dose for 21 d. |
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