BACKGROUND The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. METHODS Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. RESULTS The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 μg/mL at 4 hours and 19.5 ± 13.0 μg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 μg/mL at 4 hours and 17.7 ± 15.4 μg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S . aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S . aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. CONCLUSIONS The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. LEVEL OF EVIDENCE Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

中文翻译：

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TKA 后 24 小时的体内关节内抗生素浓度低于大多数细菌的最低抑制浓度：一项市售骨水泥的随机研究。


背景 使用抗生素负载骨水泥 （ALBC） 来帮助降低初次全膝关节置换术 （TKA） 后的感染风险是有争议的。缺乏关于 ALBC 洗脱特性的体内数据。我们旨在确定 2 种市售 ALBC 的抗生素浓度是否满足常见感染生物的最低抑制浓度 （MIC） 和最低生物膜根除浓度 （MBEC）。方法 45 名接受 TKA 的患者被随机分配接受以下 1 项：不含抗生素的骨水泥（阴性对照;n = 5），含有 1 g 妥布霉素的市售制剂 （n = 20），或含有 0.5 g 庆大霉素的市售制剂 （n = 20）。放置关节内引流管，并在术后 4 小时和 24 小时收集液体。进行了测量抗生素浓度的自动免疫测定，并将结果与已公布的 MIC 和 MBEC 阈值进行了比较。结果 ALBC 治疗组以白人 （65%） 或黑人 （32.5%） 为主，女性占 57.5%，男性占 42.4%。庆大霉素组的平均年龄 （和标准差） 为 72.6 ± 7.2 岁，妥布霉素组为 67.6 ± 7.4 岁。妥布霉素组 4 h 时抗生素平均浓度为 55.1 ± 37.7 μg/mL，24 h 时为 19.5 ± 13.0 μg/mL，庆大霉素组 4 h 时平均浓度分别为 38.4 ± 25.4 μg/mL，24 h 时为 17.7 ± 15.4 μg/mL。时间和抗生素浓度呈负线性相关系数 （r = -0.501）。大多数参考 MIC 水平在 4 小时时达到。 然而，在 24 小时时，相当一部分患者的许多常见病原体的浓度低于 MIC，包括表皮葡萄球菌（庆大霉素：65%-100% 的患者;妥布霉素：50% -85%）、甲氧西林敏感的金黄色葡萄球菌（庆大霉素：5%-90%;妥布霉素：5%-50%）、耐甲氧西林 S .金黄色葡萄球菌（庆大霉素：5%-65%;妥布霉素：50%）、链球菌属（庆大霉素：10%-100%）和痤疮杆菌（庆大霉素：10%-65%;妥布霉素：100%）。上述范围反映了每种生物体不同菌株之间 MIC 的变化。庆大霉素浓度仅在 4 小时时达到 MBEC 阈值，仅适用于毒性最低的 S 菌株。金黄色葡萄球菌和大肠杆菌。妥布霉素浓度在任一时间点均未达到任何细菌的 MBEC 阈值。结论 TKA 后市售 ALBC 中抗生素的洗脱量迅速下降，仅在术后 4 小时，大多数病原体的平均抗生素浓度才超过 MIC。使用 TKA 后使用市售的 ALBC 可能无法提供实质性的抗菌覆盖。证据级别 治疗 I 级 .有关证据级别的完整描述，请参阅作者说明。