Study On Pharmacodynamics Of Colistin Against Three Induced Multidrug-Resistant Gram-Negative Bacteria

Colistin is a specific medicine on curing disease of gram-negative bacteria. But colistin was disused, considered its renal toxicity and neurotoxicity. In recent years, multi-drug resistant bacteria have been brought, due to the overuse of antibiotics, that brought great difficulties to the clinical treatment. The clinical value of colistin has been forced to reappraise. However, lacked of systematic research on pharmacodynamics of colistin, the guiding opinions was could not been given to veterinary clinic. By artificial induction of multi-drug resistant bacteria, the pharmacodynamic of colistin was been studied.In artificial induction of multiple drug-resistant bacteria test and multi-drug resistant bacterial resistance stability test, MIC of the after induced bacteria is four times greater than or equal to MIC of the before induced bacteria. The induction of multiple drug-resistant E. coli, Pseudomonas aeruginosa and Salmonella to ampicillin, enrofloxacin, doxycycline, gentamicin and florfenicol had been acquired.The drug-resistant of induced bacteria is stable.The bacterial concentrations of106CFU/mL was acted at the drug concentrations of0.5MIC,2MIC,4MIC,8MIC,16MIC. According to colony count at0,1,2,4,8,12and24h and according to the number of bacteria in different concentration under a single factor for multiple comparisons for2h, activity of colistin was concentration-dependent to E.coli and Salmonella, while partly concentration-dependent to Pseudomonas Aeruginos.The colistin antibacterial activity of multi-drug resistant bacteria in vitro showed that the MIC value of colistin to E.coli, Pseudomonas Aeruginosa and Salmonella was0.25,2and1ug/mL respectively. The MBC value of colistin to E.coli, Pseudomonas Aeruginosa and Salmonella was0.5,2and2ug/mL respectively. The above results indicated that colistin exerted strong and prompt bactericidal effect on the multidrug-resistant E.coli, Pseudomonas Aeruginosa and Salmonella strains.According to the model of chickens infected with multi-drug resistant bacteria disease, the ID50of the multi-resistant E.coli, Pseudomonas Aeruginosa and Salmonella was1.31×108CFU/mL,2.53x108CFU/mL and5.381×108CFU/mL respectively by the Spearman-karber counting method, on the basis of chickens infected with the clinical diagnosis and laboratory identification. In the disease models, the infective amount of multi-drug resistant E.coli, Pseudomonas Aeruginosa and Salmonella was2.62×108CFU/mL,1.01×109CFU/mL and1.08× 109CFU/mL respectively.The result of therapeutic test after artificially with multi-drug resistant bacteria to chicken, the medicine concentration reached80mg/L (high dose),40mg/L (middle dose) and20mg/L (low dose). the death rate, the effective rate, the cure rate and the growth rate was statistically analysised. The dose of40mg/L was a reference dose of multi-resistant E.coli disease treatment.The dose of80mg/L was a reference dose of multi-resistant Pseudomonas Aeruginosa and Salmonella disease treatment respectively.Colistin exerted therapeutic effect on the multidrug-resistant Pseudomonas Aeruginosa, E.coli strains and Salmonella diease. This study can provide the theoretical and experimental basis of pharmacodynamic for the clinical application of colistin.