From the Department of Orthopedic Surgery, Limoges University Hospital Center, Limoges, France (Dr. Marcheix, Dr. Fiorenza), the Department of Baceriology, Limoges University Hospital Center (Dr. Martin), the Research Center for Artificial Biopolymers, Faculty of Pharmacy Montpellier, Montpellier, France (Dr. Leclercq) and the Department of Biochemistry, Limoges University Hospital Center (Dr. Sturtz).
J Am Acad Orthop Surg. 2018 Aug 15;26(16):e349-e356. doi: 10.5435/JAAOS-D-16-00883.
Because local delivery of drugs induces high concentrations, it could be helpful to apply these delivery systems to the treatment of septic arthritis by antibiotics. Thus, a gentamicin-loaded polymer was tested in a rabbit model of Staphylococcus aureus septic arthritis.
Thirty New Zealand rabbits were split into five groups: A: infection only; B: infection and systemic gentamicin treatment; C: infection and unloaded polymer and systemic gentamicin treatment; D: infection and gentamicin-loaded polymer only; and E: no infection and unloaded polymer. After inducing nonlethal septic arthritis in the knee joint by injecting 10 colony-forming units (CFUs) of a strain of methicillin-sensitive S aureus in groups A, B, C, and D, rabbits were housed for 15 days, and then the joint capsules were removed and the remaining bacteria were counted. Bacterial load was expressed in CFUs per gram of synovial tissue. In group E, capsules were removed, and a pathologic examination was done.
At day 15, the bacterial load was 6 × 10, 2 × 10, 1.8 × 10, and 7 × 10 CFU/g of tissue for groups A, B, C, and D, respectively. Compared with the mean of groups A, B, and C, the bacterial load of group D was 4.94 units of log10 CFU/g lower than that of these groups. The bacterial load of group D was statistically significantly lower than that of the other three groups. Noticeably, two animals of group D had a nil bacterial count. In group E animals, a minimal foreign body reaction was observed around the polymer.
Gentamicin-containing microparticles were more efficient in reducing bacterial load than systemic injections of gentamicin and thus have an interesting role to play in the treatment of human arthritis. However, inserting microparticles in joints is not easy, and hydrogels might be a good alternative approach.
由于局部递药能诱导高浓度,因此将这些递药系统应用于抗生素治疗化脓性关节炎可能会有所帮助。因此,我们在金黄色葡萄球菌化脓性关节炎兔模型中测试了载庆大霉素的聚合物。
将 30 只新西兰兔分为 5 组:A 组:仅感染;B 组:感染和全身应用庆大霉素治疗;C 组:感染和未载药聚合物及全身应用庆大霉素治疗;D 组:感染和仅载药聚合物;E 组:无感染和未载药聚合物。A、B、C 和 D 组通过膝关节注射 10 个菌落形成单位(CFU)的耐甲氧西林敏感金黄色葡萄球菌菌株诱导非致死性化脓性关节炎,然后将兔饲养 15 天,取出关节囊并计数剩余细菌。细菌负荷用每克滑膜组织中的 CFU 表示。E 组取出关节囊,进行病理检查。
第 15 天,A、B、C 和 D 组的细菌负荷分别为 6×10、2×10、1.8×10 和 7×10 CFU/g 组织。与 A、B 和 C 组的平均值相比,D 组的细菌负荷低 4.94 个对数 10 CFU/g,与其他 3 组相比,D 组的细菌负荷显著降低。值得注意的是,D 组的 2 只动物的细菌计数为零。在 E 组动物中,聚合物周围观察到轻微的异物反应。
载庆大霉素的微球比全身应用庆大霉素更能有效降低细菌负荷,因此在治疗人类关节炎方面具有重要作用。然而,将微球插入关节并不容易,水凝胶可能是一种很好的替代方法。