| CVC technique has become one of the necessary means for seriously ill patients rescue for its advantages of simple operation and long indwelling time. But infection rate which is triggered by catheter also showed a trend of increased year by year, especially the separation rate of epidermis staphylococcus is reach up to 60%-80%.CRI is associated with bacteria biofilm. the formation of bacterial biofilm forced patients to pull out tube because system medicine curative effect is poor, which greatly increase the risk of patients, reduce the patient’s cure rate and increased mortality. ALT consists of filling the catheter lumen with an antibiotic solution and allowing it to dwell for a period of time, in order to sterilize the device. But on the technology treatment of CRI caused by staphylococcus epidermis relatively small, the effectiveness/appropriate concentration and time, whether produce negative effect when used also need further discussion. In order to reveal these questions, we did related research, hoping for provide scientific theoretical basis when future clinical use ALT for treatment of CRI. in this study,we use epidermis staphylococcus ATCC35984 as experimental strains which is most likely cause of CRI and Ceftazidime as ALT antibacterial solution which is commonly used in clinical carry out the reach.Objective:Firstly, comparing the effect of ALT and systemic therapy to treatment CRI caused by epidermis staphylococcus through animal experiments, at the same time, confirming the feasibility of ALT be as conventional therapy for the treatment of CRI according to test bacterial resistance^ endothelial vascular presence of lesions or not when using ALT. Secondly, this study will find the best drug solution concentration and the most effective lock time in the regular and common lock time and drug concentration, so as to provide theoretical basis for future clinical use the technology.Methods:First stage:catheters had been formed bacterial biofilm were implanted into animals,all animals be randomized into three groups. Systemic treatment group(group A):systemic Ceftazidime dosing 100 mg/kg and intraductal injection of sterile saline solution; Catheter with drug group (group B):injection of 0.3 ml Ceftazidime-heparin dosing 7.2 mg/ml in catheter lumen; Combination group (group C) method combed group A and group B. Three groups of animals stopped intervention after 8 days later and blood from peripheral and catheter will be collect at day 2,4,6,8,11 after catheter inserting, bacterial quantitative culture adopted the dilution plate counting method; the effect of remove the bacterial biofilm using argentation; content of vWF were tested by ELASA; By disc diffusion method tested whether epidermis staphylococcus isolated from the animal resistant to antibiotics. The second stage:silica gel film containing a bacterial biofilm randomized into different groups according to the different concentrations of drug intervention using the guide piece method, which is 300×MIC、600×MIC、900×MIC concentration, each group takes out silica gel film after intervention at 18 h,6 h,12 h,24 h.the most effective lock time and concentrations of ALT were compared by bacterial quantitative culture. All statistics using SPSS17.0 statistical software, bacteria count results using mean±standard deviation, T test statistical analysis of independent sample, In all cases, are thought to have statistical significance for p< 0.05.Results:(1) Catheter blood bacterial count results:during the intervention, group B and group C bacteria count results have no statistical difference, but there are significant differences between group A (p< 0.001);When stop intervention, group A count remains high, six animals counting result in group B and group C is 0 (including 4 group B, group C 5); after Stopped the intervention, the results is 0 of 9 animals in group B and group C is still 0. (2) Catheter blood bacterial count results: Before intervention, three groups animal’s peripheral blood qualitative cultures were negative, When stop intervention, all animals in group A were positive, but in group B had 2 positive cases, while group C did not appear positive case; after the intervention, there have 2 cases in group B and leases in group C. (3) Bacterial count result: there have 6 specimens bacterial count result showed 0 (4 in group B,5 in group C); argentation results:indwelling needle cavity in group A present black floc and no clear boundary between biofilm; indwelling needle cavity in group B and C which is not completely remove biofilm, it can be obviously to see the plaque and a small amount of floc, while that has completely remove biofilm had no obvious mass and black spots. (4) vWF results:2 days after catheter insertion, vWF of group A is significantly higher than that of group B and C, three groups of vWF content increased with the insertion time extension and content of vWF in group B、C between group A with statistical significance with (p< 0.001); after the intervention, the content of vWF in group B and group C continue to rise, there have significant differences among three group (p< 0.001). (5) Drug resistance:three groups no drug-resistant happen. (6) The most effective time under different concentrations: silicone film bacteria count under 300×MIC and the control group had no significant difference, bacteria count results appeared significant difference at 18h under 600xMIC,while at 12h under 900×MIC(P<0.001). (7) The most effective concentration under different time lock:three groups have statistical significant at the same locked time, P< 0.001.Conclusion:(1) ALT can effectively remove bacteria biofilm. (2) Early use ALT can reduce the occurrence of systemic infection. (3) Cooperation with systemic treatment can be effective prevent systemic infection. (4) It will not cause infection again in short term if the intraductal bacterial biofilm has been completely cleared, while it still have the possibility of recurrence infection after stop meddling if bacterial biofilm is not completely clear. (5) Using ALT won’t injure vascular endothelial cells and also does not cause bacteria resistant. (6) In a certain lock time, the higher the concentration, the stronger its ability to remove biofilm. (7) 300×MIC as ALT solution without the ability to remove bacteria biofilm, if choosing 600×MIC and 900 xMIC as ALT solution, locking 18 h and 12 h can achieve the best removal effect. |
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