Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants:: An in vitro and in vivo study
Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants:: An in vitro and in vivo study
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DOI：
10.1002/jor.20193
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发表时间：
2006-08-01
影响因子：
2.8
通讯作者：
Arens, Stephan
中科院分区：
文献类型：
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作者：
Kaelicke, Thomas;Schierholz, Joerg;Arens, Stephan
本研究的目的是获得关于抗菌和可生物降解的聚-L-丙交酯（PLLA）涂层钛板接骨术对局部感染抵抗力的影响的信息。对于我们的体外和体内实验，我们使用六孔AO DC微型骨折块钛板。植入物用可生物降解的半无定形PLLA（涂层约30 μ m厚）涂覆。它作为一种载体物质，加入抗生素或防腐剂。我们使用的抗生素是利福平和夫西地酸的组合;防腐剂是奥替尼定和Irgasan的组合。这产生了以下组：第I组：不含PLLA的六孔AO DC微型骨折块钛板;第II组：含PLLA的六孔AO DC微型骨折块钛板，不含抗生素/防腐剂;第III组：含PLLA + 3%利福平和7%夫西地酸的六孔AO DC微型骨折块钛板;第IV组：含PLLA + 2%奥替尼啶和8% Irgasan的六孔AO DC微型骨折块钛板。在体外，我们研究了PLLA涂层在6周内的降解和释放，抗生素/防腐剂从涂层中释放后的杀菌功效以及金黄色葡萄球菌对植入物的细菌粘附。在体内，我们比较了白色新西兰兔胫骨钛板接骨术后，在不同浓度（2 x 10（5）-2 x 10（8））的局部经皮细菌接种后，有或无抗菌涂层的感染率：28天后，在无菌条件下取出钛板、污染的软组织和下层骨，并定量评价细菌生长。使用具有“上下”剂量技术的逐步实验设计来调整ID 50（50%感染剂量）区域中的细菌挑战。使用双侧Fisher精确检验对两组感染率之间的差异进行统计学评价（p < 0.05）。在6周的时间内，在体外0.9%NaCl溶液中观察到PLLA涂层平均13%的连续降解。对带有抗生素或抗菌剂涂层的钛植入物进行的洗脱试验在前60分钟内产生了60%的合并抗生素或62%的合并抗菌剂的平均释放值。随后，合并抗生素和抗菌剂的释放速度要慢得多，但仍持续数天和数周。在42天的测试期结束时，20%的掺入的抗生素和15%的掺入的防腐剂尚未从涂层中释放。抗生素/防腐剂的抗菌效果不会因将其整合到PLLA涂层中而丧失。体内研究中的总体感染率为50%。对于组I和组II，感染率均为83%（10/12只动物）。在具有抗菌涂层的组III和组IV中，感染率均为17%（2/12只动物）。抗菌涂层组III和IV中的ID 50记录为1 x 10（8）CFU，而无抗菌涂层组I和II中的ID 50值分别为1 x 10（6）CFU低一百倍。带和不带抗菌涂层组之间的差异具有统计学显著性（p = 0.033）。在钛板上使用抗菌可生物降解的PLLA涂层，在体外和体内研究中可以证明感染率的显着降低。据我们所知，我们第一次能够在标准化和可重复的条件下证明，抗菌涂层与抗生素涂层一样可以降低感染率。考虑到抗生素诱导的细菌耐药性问题，我们因此认为具有相同有效性水平的抗菌涂层是有利的。(c)2006骨科研究学会。出版社：Wiley Periodicals，Inc.
The purpose of this study was to acquire information about the effect of an antibacterial and biodegradable poly-L-lactide (PLLA) coated titanium plate osteosynthesis on local infection resistance. For our in vitro and in vivo experiments, we used six-hole AO DC minifragment titanium plates. The implants were coated with biodegradable, semiamorphous PLLA (coating about 30 mu m thick). This acted as a carrier substance to which either antibiotics or antiseptics were added. The antibiotic we applied was a combination of Rifampicin and fusidic acid; the antiseptic was a combination of Octenidin and Irgasan. This produced the following groups: Group I: six-hole AO DC minifragment titanium plate without PLLA; Group II: six-hole AO DC minifragment titanium plate with PLLA without antibiotics/antiseptics; Group III: six-hole AO DC minifragment titanium plate with PLLA + 3% Rifampicin and 7% fusidic acid; Group IV: six-hole AO DC minifragment titanium plate with PLLA + 2% Octenidin and 8% Irgasan. In vitro, we investigated the degradation and the release of the PLLA coating over a period of 6 weeks, the bactericidal efficacy of antibiotics/antiseptics after their release from the coating and the bacterial adhesion of Staphylococcus aureus to the implants. In vivo, we compared the infection rates in white New Zealand rabbits after titanium plate osteosynthesis of the tibia with or without antibacterial coating after local percutaneous bacterial inoculations at different concentrations (2 x 10(5)-2 x 10(8)): The plate, the contaminated soft tissues and the underlying bone were removed under sterile conditions after 28 days and quantitatively evaluated for bacterial growth. A stepwise experimental design with an "up-and-down" dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the differences between the infection rates of both groups was performed using the two-sided Fisher exact test (p < 0.05). Over a period of 6 weeks, a continuous degradation of the PLLA coating of 13%, on average, was seen in vitro in 0.9% NaCl solution. The elution tests on titanium implants with antibiotic or antiseptic coatings produced average release values of 60% of the incorporated antibiotic or 62% of the incorporated antiseptic within the first 60 min. This was followed by a much slower, but nevertheless continuous, release of the incorporated antibiotic and antiseptic over days and weeks. At the end of the test period of 42 days, 20% of the incorporated antibiotic and 15% of the incorporated antiseptic had not yet been released from the coating. The antibacterial effect of the antibiotic/antiseptic is not lost by integrating it into the PLLA coating. The overall infection rate in the in vivo investigation was 50%. For Groups I and II the infection rate was both 83% (10 of 12 animals). In Groups III and IV with antibacterial coating, the infection rate was both 17% (2 of 12 animals). The ID50 in the antibacterial coated Groups III and IV was recorded as 1 x 10(8) CFU, whereas the ID50 values in the Groups I and II without antibacterial coating were a hundred times lower at 1 x 10(6) CFU, respectively. The difference between the groups with and without antibacterial coating was statistically significant (p = 0.033). Using an antibacterial biodegradable PLLA coating on titanium plates, a significant reduction of infection rate in an in vitro and in vivo investigation could be demonstrated.For the first time, to our knowledge, we were able to show,under standardized and reproducible conditions, that an antiseptic coating leads to the same reduction in infection rate as an antibiotic coating. Taking the problem of antibiotic-induced bacterial resistance into consideration, we thus regard the antiseptic coating, which shows the same level of effectiveness, as advantageous. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.