| Porcine contagious pleuropneumia is a respiratory infectious disease caused by different serogroups of Actinobacillus pleuropneumoniae.With the large-scale development of China's pig industry,the outbreak of Porcine contagious pleuropneumia will bringhuge losses to pig farmers.Tylosin is a macrolide antibiotic that is effective in the treatment of respiratory diseases caused by bacterial infections.Tylosin is widely used in clinical treatment,which greatly reduces the losses of pig industry.However,in recent years,due to the increasing use of tylosin in clinical,the expansion of the use range,unreasonable and uncontrolled abuse,tylosinhas developed resistance to the treatment of bacterial respiratory diseases,and there is a lack of new antibiotics as clinical alternative treatment drugs.Therefore,in order to slow down the drug resistance of Actinobacillus pleuropneumoniae to tylosin and protected the effectiveness of tylosin,it is necessary to establish the scientific antibiotic resistance testing standards and formulate rational clinical drug delivery programs.This study analyzed the rapid and accurate identification method of Actinobacillus pleuropneumoniae,and showed that MALDI TOF microbial identification and PCR molecular identification methodshad thehighest accuracy,and the operation was simple and fast.In this research the virulence of the serotype of APP strain was identified and the virulence of the epidemic pathogenic serotype was compared.The results determined that the virulence of serotype 1 was the most virulent.The in vitro pharmacology of tylosin against Actinobacillus pleuropneumoniae was conducted,the minimum mutant prevention concentration(MPC)in vitro was determined to be 41 ?g/mL,and the mutant selection window(MSW)was 32-41 ?g/mL.The results showed that Actinobacillus pleuropneumoniae exposed to different concentrations of 2MIC?4MIC tylosin solutions,then remove tylosin after 1h and 2h,and calculate the PAE of tylosin against Actinobacillus pleuropneumoniae.The PAEs of Actinobacillus pleuropneumoniae exposed to tylosin for 1h were 1.25h and 1.87h,2.06h and 3.17h respectively for 2h,which showed that the tylosin against Actinobacillus pleuropneumoniaehad a prolonged PAE to Actinobacillus pleuropneumoniae;The in vitro and in vivo bactericidal killing curves in vitro and in vivo of APP were determined.According to the bactericidal killing curves,the antibacterial effects of tylosin against Actinobacillus pleuropneumoniae was time-dependent.In vitro,the above MIC values showed a significant increase in bactericidal effect with the increase in the action time of tylosin against Actinobacillus pleuropneumoniae.In ex vivo,tylosinhad the strongest antibacterial activity against APP at 1.5h.That can confirm that the pivotal PK/PD paramerer of tylosin against APP is AUC/MIC.The drug sensitivity of tylosin against actinobacillus pleuropneumoniae in 165 strains was studied,and the wild type cutoff of tylosin against APP was established.The MIC was analyzed by ECOFFinder software,and the wild type cutoff of actinobacillus pleuropneumoniae was determined to be 32 ?g/mL.The MIC of 45 strains of common antibiotics against actinobacter pneumothorax which preserved in the laboratory was determined.The results showed that APP washighly sensitive to roxithromycin andhad ahigh drug resistance rate to tetracycline.APP ishighly sensitive to enoxacin,and less sensitive to sulfadiazine and sulfisoxazole.The antibacterial effect of tylosin against actinobacillus pleuropneumoniae was tested in vitro and in vivo.This study provided a scientific basis for drug resistance monitoring of actinobacillus pleuropneumoniae.The pharmacokinetic and pharmacodynamic characteristics of tylosin inhealthy pigs and diseased pigs were studied.By data fitting with Winionlin software,it was found that the expression of tylosin inhealthy pigs and diseased pigs was non-atrioventricular model.As the result showed that tylosin was time-dependent,so the main pharmacokinetic parameters of tylosin inhealthy pigs and diseased pigs were as follows: eliminationhalf-life T1/2 = 1.719h,2.683h,AUC= 8.710h*?g/mL,6.673h*?g/mL,average residence time MRT=3.930h,6.231h.Inhealthy pigs,thehighest blood concentration Cmax=1.770?g/mL was reached after 1.5h.Thehighest blood concentration Cmax=1.611 ?g /mL was reached in the diseased pigs after 1h,indicating that the absorption of tylosin was fast,and can quickly reach thehighest blood concentration in the diseased pigs.The main pharmacokinetic and pharmacodynamic parameter values ofhealthy pigs and diseased pigs were calculated by combining the in vitro pharmacodynamic MIC with the in vivo pharmacokinetic data ofhealthy pigs and diseased pigs,respectively: AUC/MIC=0.544,0.209,Cmax/MIC=0.111,0.051.Combined with in vivo and ex vivo pharmacokinetic and pharmacodynamic parameters,the clinical dose of tylosin for the treatment of Porcine contagious pleuropneumia was 6.246 mg/kg ~ 18.74 mg/kg. |
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