万古霉素和肝素混合液的稳定性及体外抗菌活性的研究

In-vitro stability and antimicrobial activity of vancomycin solution mixed with heparin

目的体外实验观察万古霉素和肝素混合液的稳定性以及抗菌活性,为治疗血液透析患者导管相关性感染的抗生素封管技术提供理论依据。方法万古霉素和肝素钠注射液混合配制成含不同浓度万古霉素和相同浓度肝素的混合液,保存于37℃恒温箱内,依次在0min、15min、30min、24h、48h取出,利用肉眼观察以及在澄明度检查仪上检查混合液的澄明度。选择特定浓度的混合液,分别在0h、2h、8h、24h、48h比较该混合液和同等浓度的万古霉素生理盐水溶液对标准参考菌株金黄色葡萄球菌(ATCC29213)的抑菌圈。结果 随着万古霉素浓度的降低,混合液的浑浊物逐渐减少直至澄清,自万古霉素浓度为10mg/ml始混合液澄清。万古霉素浓度为20mg/ml和10mg/ml的万古霉素肝素混合液均出现较大抑菌圈,与同浓度的万古霉素生理盐水溶液抑菌圈直径差异无统计学意义(P>0.05)。同一试剂在不同时间点抑菌圈直径差异无统计学意义(P>0.05)。结论万古霉素与肝素混合有无发生浑浊现象与万古霉素的浓度相关,浓度为10mg/ml的万古肝素混合液,性状稳定,抑菌作用明显,可以作为导管相关菌血症,特别是金黄色葡萄球菌感染的导管相关菌血症的封管液。

Objective We studied the in-vitro stability and antimicrobial activity of vancomycin solution mixed with heparin, to predict its efficacy when used in vancomycin/heparin lock manipulation to prevent catheter-related bacteremia among maintenance hemodialysis patients. Methods Heparin was mixed with various concentrations ofvancomycin, and stored at 37？ for 0 min, 15 min, 30 min, 24 h, or 48 h. These mixtures were then examined for visual precipitation and clarity by a clarity instrument. One of the mixtures stored at 37？ for 0 min, 15 min, 30 min, 24 h, and 48 h was assayed for the diameter ofbacterio- static circle against staphylococcus aureus （ATCC 29213）, using the same vancomycin concentration in normal saline as the standard for comparison. Results Precipitates in the mixture reduced gradually with the decrease of vancomycin concentration, and disappeared completely in the mixtures containing 〈 10 mg/ ml vancomycin. The diameters ofbacteriostatic circle from the mixtures containing 10 and 20 mg/ml vanco- mycin were similar to those from normal saline containing 10 and 20 mg/ml vancomycin, respectively （P 〉 0.05）. In addition, the diameters ofbacteriostatic circle were statistically indifferent from one mixture stored at 37℃ for various period of time. Conclusions The degree of precipitation in vancomycin solution mixed with heparin is vancomycin concentration dependent. The mixture containing 10 mg/ml vancomycin is stable with sufficient bacteriostatic activity, and can be used as the vancomycin/heparin lock solution to prevent catheter-related bacteremia, especially that due to staphylococcus aureus infection.