Effects And Drug Resistances Of Vancomycin Administered In Different Dosage In Rats MRSA Pneumonia Model

Objective : In order to evaluate the Pharmacokinetic/pharmacodynamic characteristic, the curative effects and resistance of vancomycin administered in different dosage in rats MRSA pneumonia model, for the clinical application of vancomycin treatment Staphylococcus aureus of infection provide experimental basis.Methods: With intratracheal instillation method, ATCC43300 were used to establish rat pneumonia model. According to dose, 76 adult female Sprague-Dawley rats were separated into four groups:Ⅰgroup (40 mg / kg qd),Ⅱgroup (20 mg / kg qd), III group (10mg/kg qd), IV group (20 mg / kg bid). Therapy was started 16 hours after bacterial inoculation and continued for 6 days; Plasma samples were collected at 10,20,30,60,90,120 min after drug administration, concentrations in serum were determined by using microbiological assays, drawn Pharmacokinetics curve calculated PK / PD parameter, such as AUC / MIC, Cmax / MIC, T> MIC, evaluation of efficacy, and analysis of the relationship between PK / PD parameters and efficacy; The efficacies were evaluated 6 hours later by the survival rate and the viable bacterial counts of the lungs after the end of treatment; The agar enrichment method to determine MPC of methicillin-resistant Staphylococcus aureus standard strain ATCC43300, the agar dilution method to determine MIC,MIC99 of vancomycin. To investigate MSW of ATCC43300 and efficacy of combination therapy to it, and analysis of the relationship between MSW and bacterial resistances.Results: 1) The statistics show that on the whole of rats in each group the survival rate gradually increased with the dose increased, but the difference was not statistically significant (p>0.05); 2) The colony counts in lung homogenates of all treatment groups were lower than the model group(p<0.05); the bacterial counts of the lungs in groupⅠand groupⅡhave no significant difference(p>0.05); however, have significant difference in groupⅠ,groupⅡand group III (p<0.05); the bacterial counts of the lungs in groupⅠand group IV have no significant difference(p>0.05). 3) MIC of Strains increased after treatment in groupⅡand group III, and with the model control group were significant difference(p<0.05), pharmacokinetic curve of the groups analysis showed that the concentration in plasma ofⅡgroup and group III were within the MSW; Levofloxacin combined with vancomycin decreased the MSW of vancomycin to staphylococcus aureus ATCC43300 for 2～4 times. 4) PK / PD analysis showed that the relationship between AUC / MIC , Cmax / MIC and efficacy.Conclusion: There were no differences in the treatment of rats pneumonia model infected by ATCC4300 among group I, group II and group IV, all the previous groups'effects superior to Group III, but the MIC of strain in group II, group III increased after treatment, suggesting that it could induce resistance more easily. Therefore, in the course of treatment necessary to monitor the blood concentration, according to the results of blood concentration administration adjustment programmes to achieve the best anti-infection treatment. Combination therapy can make to reduce the MSW of Staphylococcus aureus,combination therapy for drug-resistant pathogensis probably among the more effective means of decreasing the development of resistance, it is a better choice.