Gallo J, Bogdanová K, Šiller M, Švábová M, Lošťák J, Kolář M
Ortopedická klinika LF UP a FN Olomouc.
Acta Chir Orthop Traumatol Cech. 2013;80(1):69-76.
Prosthetic joint infection is a feared complication in total hip arthroplasty. The use of antibiotic-impregnated bone cement is the important part of preventive and therapeutic strategies. At present a number of commercial bone cements are available and support of their use by the results of experimental trials and clinical studies has varied. In relation to this issue we studied essential microbiological and pharmacological characteristics of VancogenX in comparison with gentamicin-loaded bone cement used conventionally.
Based on a previously described protocol, we tested pellets of four commercial bone cements, namely, Hi-Fatigue G, Palacos R+G, VancogenX, and Palacos R as a control. Bone cement was prepared in a vacuum-mixing system. The strains used for bacterial load included Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. Each cement was tested for its antimicrobial and antibiofilm activities and the results were evaluated by standard methods. In addition, we investigated time-related release of gentamicin and vancomycin from the bone cements tested.
All antibiotic-loaded cement pellets were able to prevent growth of the bacterial strains tested. The bactericidal effect lasted for several days in relation to the bacterial species and cement used, with the exception of S. epidermidis whose growth was inhibited by gentamicin-loaded cement only for one day. The antibiotic-loaded pellets also prevented the formation of a biofilm for 24 hours at least. The major amount of vancomycin (32.915 mg/l) was released from VancogenX to MH medium within 24 hours and the last measureable amount (4.327 mg/l) was recorded at 48 hours after the start of the experiment. In physiological saline the highest level of vancomycin was 139.852 mg/ml measured at 24 hours, and the antibiotic was detectable at a level of 2.334 mg/ml as late as 8 days after the experiment started. Release of gentamicin from VancogenX was as follows: the 24-hour level was higher in MH medium than physiological saline (178 versus 131.4 mg/ml); however, gentamicin was still detectable in physiological saline at 192 hours after the start of the experiment while no gentamicin was found in MH medium after 72 hours.
The antimicrobial effect of VancogenX bone cement was not an unexpected finding since both gentamicin and vancomycin have been used with bone cement for a long time and their combination is optimal in terms of preventing prosthetic joint infection. However, there is a disputable issue of poor release of vancomycin from bone cement. In MH medium we were able to detect the vancomycin released from VancogenX only for two days after the initial rapid elution while its release into physiological saline seemed to be slower but much longer. It is possible that more vancomycin is released from bone cement, but this amount is immediately bound to proteins in the cement vicinity and this process is not detectable by any analytical method.
The bone cement VancogenX showed excellent antimicrobial and antibiofilm properties and can be recommended for use in orthopaedic practice. Therapy of prosthetic joint infection is the main indication. Extension of the indication to the prevention of prosthetic joint infection in high-risk patients should be preceded by biomechanical studies demonstrating that the cement is appropriate for long-term implant fixation.
人工关节感染是全髋关节置换术中令人担忧的并发症。使用抗生素骨水泥是预防和治疗策略的重要组成部分。目前有多种商用骨水泥可供选择,实验试验和临床研究结果对其使用的支持程度各不相同。针对这一问题,我们将VancogenX的基本微生物学和药理学特性与传统使用的庆大霉素骨水泥进行了比较研究。
基于先前描述的方案,我们测试了四种商用骨水泥的小球,即Hi-Fatigue G、Palacos R+G、VancogenX以及作为对照的Palacos R。骨水泥在真空混合系统中制备。用于细菌负荷的菌株包括金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、铜绿假单胞菌和大肠杆菌。对每种骨水泥进行抗菌和抗生物膜活性测试,并通过标准方法评估结果。此外,我们研究了受试骨水泥中庆大霉素和万古霉素的时间相关释放情况。
所有含抗生素的骨水泥小球均能抑制受试细菌菌株的生长。根据所使用的细菌种类和骨水泥不同,杀菌效果可持续数天,但表皮葡萄球菌除外,其生长仅被含庆大霉素的骨水泥抑制一天。含抗生素的小球至少在24小时内还能防止生物膜形成。实验开始后24小时内,VancogenX中有大量万古霉素(32.915mg/l)释放到MH培养基中,在48小时记录到最后可测量量(4.327mg/l)。在生理盐水中,万古霉素在24小时时的最高水平为139.852mg/ml,在实验开始后8天仍可检测到抗生素,水平为2.334mg/ml。VancogenX中庆大霉素的释放情况如下:在MH培养基中24小时的水平高于生理盐水(178对131.4mg/ml);然而,在实验开始后192小时生理盐水中仍可检测到庆大霉素,而在MH培养基中72小时后未发现庆大霉素。
VancogenX骨水泥的抗菌作用并非意外发现,因为庆大霉素和万古霉素长期以来一直与骨水泥联合使用,且它们在预防人工关节感染方面的组合是最佳的。然而,关于万古霉素从骨水泥中释放不佳存在争议。在MH培养基中,我们仅在初始快速洗脱后的两天内检测到VancogenX释放的万古霉素,而其释放到生理盐水中似乎较慢但持续时间更长。有可能骨水泥释放出更多的万古霉素,但这部分量立即与骨水泥附近的蛋白质结合,任何分析方法都无法检测到这一过程。
骨水泥VancogenX具有出色的抗菌和抗生物膜特性,可推荐用于骨科实践。人工关节感染的治疗是主要适应症。在将适应症扩展到高危患者人工关节感染的预防之前,应先进行生物力学研究,证明该骨水泥适合长期植入固定。