Müller Gerald, Kramer Axel
Institute of Hygiene and Environmental Medicine, University of Greifswald, W.-Rathenau-Str. 49a, D-17487 Greifswald, Germany.
J Antimicrob Chemother. 2008 Jun;61(6):1281-7. doi: 10.1093/jac/dkn125. Epub 2008 Mar 25.
To assess the suitability of an antiseptic agent, both the microbicidal activity and the cytotoxic effect must be taken into consideration to derive biocompatible antibacterial agents.
We defined the biocompatibility index (BI) by measuring the antibacterial activity against the test organisms Escherichia coli and Staphylococcus aureus and, in parallel, the cytotoxicity on cultured murine fibroblasts. The antiseptic agents tested were benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHX), mild silver protein (MSP), octenidine dihydrochloride (OCT), polyhexamethylene biguanide (PHMB), povidone iodine in solution [PVP-I(s)], povidone iodine in ointment [PVP-I(o)], silver nitrate (AgNO(3)), silver (I) sulfadiazine (SSD) and triclosan (TRI). Assays were carried out for 30 min of exposure at 37 degrees C in the presence of cell culture medium containing 10% fetal bovine serum. The resulting dimensionless BI was defined as the ratio of the concentration at which 50% of the murine fibroblasts are damaged and the microbicidal effect producing at least 3 log(10) (99.9%) reduction.
The resulting rank ordering of BI for the ratio of fibroblast cytotoxicity to E. coli toxicity was OCT > PHMB > CHX > PVP-I(o) > PVP-I(s) > BAC > CPC > TRI > MSP and that to S. aureus was OCT > PHMB > CHX > CPC > PVP-I(o) > BAC > PVP(s) > TRI > MSP. OCT and PHMB were the most suitable agents with a BI greater than 1.
The BI presented may be a useful tool to evaluate antiseptic agents for use in clinical practice.
为评估一种防腐剂的适用性,必须同时考虑其杀菌活性和细胞毒性效应,以获得生物相容性抗菌剂。
我们通过测量对测试微生物大肠杆菌和金黄色葡萄球菌的抗菌活性,并同时测量对培养的鼠成纤维细胞的细胞毒性,来定义生物相容性指数(BI)。所测试的防腐剂有苯扎氯铵(BAC)、西吡氯铵(CPC)、葡萄糖酸洗必泰(CHX)、蛋白银(MSP)、盐酸奥替尼啶(OCT)、聚六亚甲基双胍(PHMB)、溶液型聚维酮碘[PVP-I(s)]、软膏型聚维酮碘[PVP-I(o)]、硝酸银(AgNO₃)、磺胺嘧啶银(SSD)和三氯生(TRI)。在含有10%胎牛血清的细胞培养基存在下,于37℃暴露30分钟进行测定。所得无量纲BI定义为使50%的鼠成纤维细胞受损的浓度与产生至少3 log₁₀(99.9%)减少的杀菌效果的浓度之比。
成纤维细胞细胞毒性与大肠杆菌毒性之比的BI排序结果为OCT > PHMB > CHX > PVP-I(o) > PVP-I(s) > BAC > CPC > TRI > MSP,而成纤维细胞细胞毒性与金黄色葡萄球菌毒性之比的排序为OCT > PHMB > CHX > CPC > PVP-I(o) > BAC > PVP(s) > TRI > MSP。OCT和PHMB是最合适的药剂,BI大于1。
所提出的BI可能是评估临床实践中使用的防腐剂的有用工具。