Saleh Mghir A, Crémieux A C, Bleton R, Ismael F, Manteau M, Dautrey S, Massias L, Garry L, Sales N, Mazière B, Carbon C
Hôpital Bichat Claude-Bernard, Institut National de la Santé et de la Recherche Médicale, Unité 13, Paris, France.
Antimicrob Agents Chemother. 1998 Nov;42(11):2830-5. doi: 10.1128/AAC.42.11.2830.
Prosthesis infections are difficult to cure. Infection with methicillin-resistant staphylococci is becoming more common in patients with orthopedic implants. Using a recently developed model of methicillin-resistant Staphylococcus aureus (MRSA) infection of a knee prosthesis, we compared the efficacies of teicoplanin and vancomycin. [14C]teicoplanin diffusion in this model was also studied by autoradiography. A partial knee replacement was performed with a silicone implant fitting into the intramedullary canal of the tibia, and 10(7) CFU of MRSA was injected into the knee. Treatment with teicoplanin or vancomycin (20 or 60 mg/kg of body weight, respectively, given intramuscularly twice daily) was started 7 days after inoculation and was continued for 7 days. The teicoplanin and vancomycin MICs for MRSA were 1 microg/ml. Mean peak and trough levels in serum were 39.1 and 23.5 microg/ml, respectively, for teicoplanin and 34.4 and 18.5 microg/ml, respectively, for vancomycin. Fifteen days after the end of therapy, the animals were killed and their tibias were removed, pulverized, and quantitatively cultured. Teicoplanin and vancomycin significantly reduced (P < 0. 05) the bacterial density (2.7 +/- 1.3 and 3.3 +/- 1.6 log10 CFU/g of bone, respectively) compared to those for the controls (5.04 +/- 1.4 log10 CFU/g of bone). The bacterial covents of teicoplanin- and vancomycin-treated rabbits were comparable. The [14C]teicoplanin autoradiographic diffusion patterns in rabbits with prostheses, two of which were uninfected and two of which were infected, were studied 15 days after inoculation. Sixty minutes after the end of an infusion of 250 microCi of [14C]teicoplanin, autoradiography showed that in the infected animals, the highest levels of radioactivity were located around the prosthesis and in the periosteum, bone marrow, and trabecular bone. Radioactivity was less intense in epiphyseal disk cartilage, femoral cartilage, articular ligaments, and muscles and was weak in compact bone. A similar distribution pattern was seen in uninfected rabbits. Thus, teicoplanin may represent an effective alternative therapy for the treatment of these infections.
假体感染难以治愈。耐甲氧西林葡萄球菌感染在接受骨科植入物的患者中越来越常见。我们使用最近开发的膝关节假体耐甲氧西林金黄色葡萄球菌（MRSA）感染模型，比较了替考拉宁和万古霉素的疗效。还通过放射自显影术研究了[14C]替考拉宁在该模型中的扩散情况。使用适合胫骨髓内管的硅胶植入物进行部分膝关节置换，并向膝关节内注射10(7) CFU的MRSA。接种7天后开始用替考拉宁或万古霉素治疗（分别为20或60 mg/kg体重，每日两次肌肉注射），持续7天。MRSA对替考拉宁和万古霉素的MIC均为1 μg/ml。替考拉宁血清中的平均峰浓度和谷浓度分别为39.1和23.5 μg/ml，万古霉素分别为34.4和18.5 μg/ml。治疗结束15天后，处死动物并取出胫骨，粉碎后进行定量培养。与对照组（5.04 +/- 1.4 log10 CFU/g骨）相比，替考拉宁和万古霉素显著降低了（P < 0.05）细菌密度（分别为2.7 +/- 1.3和3.3 +/- 1.6 log10 CFU/g骨）。替考拉宁和万古霉素治疗的兔子的细菌含量相当。在接种15天后，研究了接种[14C]替考拉宁250 μCi输注结束60分钟后，装有假体的兔子（其中两只未感染，两只感染）的[14C]替考拉宁放射自显影扩散模式。放射自显影显示，在感染动物中，最高放射性水平位于假体周围以及骨膜、骨髓和小梁骨中。骨骺盘软骨、股骨软骨、关节韧带和肌肉中的放射性较弱，密质骨中的放射性很弱。在未感染的兔子中也观察到类似的分布模式。因此，替考拉宁可能是治疗这些感染的一种有效替代疗法。
