Li Xuwen, Lai Junhao, Yang Xue, Xu Hao, Xiang Shuai
Department of Traumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China.
J Orthop Surg Res. 2024 Dec 19;19(1):856. doi: 10.1186/s13018-024-05357-9.
This study aimed to elucidate the safety and intra-articular elution profiles of vancomycin and gentamicin bone cement in patients undergoing primary total knee arthroplasty (TKA), with a focus on serum safety thresholds and therapeutic efficacy.
Consecutive patients who underwent unilateral primary TKA were prospectively enrolled. The implants were fixed using gentamicin-impregnated bone cement, and after arthrotomy closure, 1000 mg of vancomycin suspended in 25 mL of normal saline was directly injected into the joint. Peripheral venous blood and drain fluid samples were collected 2, 8, and 24 h postoperatively. The serum and intra-articular concentrations of vancomycin and gentamicin were analyzed using liquid chromatography-tandem mass spectrometry within 24 h.
Clinical data reflecting renal and liver function were recorded preoperatively, and at 24 and 72 h postoperatively. A total of 100 patients were included. At 2, 8, and 24 h postoperatively, the serum vancomycin concentration was 7.0 ± 2.0, 5.7 ± 1.8, and 3.6 ± 1.4 µg/mL, respectively, while the intra-articular concentration was 468.5 (interquartile range [IQR] 286.0 to 774.8), 139.5 (IQR 52.0 to 295.3), and 34.4 (IQR 22.2 to 56.8) µg/mL, respectively; 33.2 (IQR 19.5 to 80.5) mg vancomycin was lost in drainage fluid at 24 h postoperatively. For gentamicin, the overall intra-articular concentration was 70.4 (IQR 35.4 to 109.2), 33.8 (IQR 17.8 to 73.9), and 21.1 (IQR 12.2 to 36.0) µg/mL at 2, 8, and 24 h postoperatively, respectively, with an undetectable serum concentration. No cases of acute renal injury, liver injury, ototoxicity, or anaphylaxis were observed.
Intra-articular injection of 1000 mg vancomycin after arthrotomy closure combined with gentamicin-impregnated bone cement provided a therapeutic intra-articular concentration while avoiding systemic toxicity over the initial 24 h after primary TKA. Therefore, intra-articular vancomycin administration may offer a safer alternative to intravenous antibiotics, reducing systemic toxicity; however, further large-scale studies are necessary.
ClinicalTrials. Gov (registration number: NCT05338021).
本研究旨在阐明万古霉素和庆大霉素骨水泥在初次全膝关节置换术（TKA）患者中的安全性和关节内洗脱情况，重点关注血清安全阈值和治疗效果。
前瞻性纳入连续接受单侧初次TKA的患者。使用含庆大霉素的骨水泥固定植入物，关节切开术关闭后，将1000mg万古霉素悬浮于25mL生理盐水中直接注入关节。术后2、8和24小时采集外周静脉血和引流液样本。术后24小时内使用液相色谱 - 串联质谱法分析万古霉素和庆大霉素的血清和关节内浓度。
术前、术后24小时和72小时记录反映肾功能和肝功能的临床数据。共纳入100例患者。术后2、8和24小时，血清万古霉素浓度分别为7.0±2.0、5.7±1.8和3.6±1.4μg/mL，而关节内浓度分别为468.5（四分位数间距[IQR]286.0至774.8）、139.5（IQR 52.0至295.3）和34.4（IQR 22.2至56.8）μg/mL；术后24小时引流液中损失33.2（IQR 19.5至80.5）mg万古霉素。对于庆大霉素，术后2、8和24小时关节内总体浓度分别为70.4（IQR 35.4至109.2）、33.8（IQR 17.8至73.9）和21.1（IQR 12.2至36.0）μg/mL，血清浓度未检测到。未观察到急性肾损伤、肝损伤、耳毒性或过敏反应病例。
关节切开术关闭后关节内注射1000mg万古霉素联合含庆大霉素的骨水泥在初次TKA后的最初24小时内提供了治疗性关节内浓度，同时避免了全身毒性。因此，关节内给予万古霉素可能为静脉使用抗生素提供更安全的替代方案，降低全身毒性；然而，需要进一步的大规模研究。
ClinicalTrials.Gov（注册号：NCT05338021）
