Levack Ashley E, Turajane Kathleen, Yang Xu, Miller Andy O, Carli Alberto V, Bostrom Mathias P, Wellman David S
Orthopaedic Trauma Service (A.E.L. and D.S.W.), Musculoskeletal Integrity Program (K.T., X.Y, A.V.C., and M.P.B.), Infectious Diseases (A.O.M.), and Adult Reconstruction (A.V.C. and M.P.B.), Hospital for Special Surgery, New York, NY.
Loyola University Medical Center, Maywood, Illinois.
J Bone Joint Surg Am. 2021 Sep 15;103(18):1694-1704. doi: 10.2106/JBJS.20.00011.
Amikacin, meropenem, minocycline, and fosfomycin have potential clinical utility for orthopaedic infections; however, their suitability for use in polymethylmethacrylate (PMMA) is poorly understood. The purpose of this study was (1) to quantify the thermal stability of these antibiotics at clinically relevant temperatures and (2) to determine the elution pharmacodynamics of these alternative antibiotics in vitro from PMMA beads of different sizes.
Polymerization temperatures of 10-mm PMMA beads were measured over time to generate a simulated heating curve. Aqueous solutions of tobramycin, amikacin, meropenem, minocycline, and fosfomycin were subjected to the temperature curves, followed by incubation at 37°C. Minimum inhibitory concentrations of each antibiotic were evaluated against Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. High-dose 4.5-mm, 6-mm, and 10-mm antibiotic-laden PMMA beads (10% antibiotic by weight) were submerged individually in a phosphate-buffered saline solution and incubated at 37°C. Antibiotic elution was determined with use of high-performance liquid chromatography with mass spectrometry.
Tobramycin, amikacin, and fosfomycin demonstrated thermal stability and maintained antimicrobial activity for 28 days. Minocycline and meropenem lost antimicrobial activity against all 3 organisms after 48 hours and 7 days, respectively. Elution concentrations, rates, and cumulative drug mass for tobramycin, amikacin, and meropenem were orders of magnitude higher than minocycline and fosfomycin at each time point.
This study identified notable differences in thermal stability and elution among antibiotics used to treat infections. Amikacin exhibited activity similarly to tobramycin. Meropenem demonstrated favorable elution kinetics and thermal stability in the initial 7-day period.
Amikacin and meropenem show pharmacologic promise as potential acceptable alternatives for local delivery in PMMA for treatment of orthopaedic infections. Further work to establish clinical relevance and utility is needed.
阿米卡星、美罗培南、米诺环素和磷霉素在骨科感染中具有潜在的临床应用价值；然而，它们在聚甲基丙烯酸甲酯（PMMA）中的适用性却鲜为人知。本研究的目的是：（1）量化这些抗生素在临床相关温度下的热稳定性；（2）测定这些替代抗生素在体外从不同尺寸的PMMA珠粒中的洗脱药效学。
随时间测量10毫米PMMA珠粒的聚合温度，以生成模拟加热曲线。将妥布霉素、阿米卡星、美罗培南、米诺环素和磷霉素的水溶液置于该温度曲线上，然后在37℃下孵育。评估每种抗生素对金黄色葡萄球菌、大肠杆菌和鲍曼不动杆菌的最低抑菌浓度。将高剂量（按重量计含10%抗生素）的4.5毫米、6毫米和10毫米载抗生素PMMA珠粒分别浸入磷酸盐缓冲盐溶液中，并在37℃下孵育。使用高效液相色谱-质谱联用仪测定抗生素洗脱情况。
妥布霉素、阿米卡星和磷霉素表现出热稳定性，并在28天内保持抗菌活性。米诺环素和美罗培南分别在48小时和7天后对所有3种微生物失去抗菌活性。在每个时间点，妥布霉素、阿米卡星和美罗培南的洗脱浓度、速率和累积药物量比米诺环素和磷霉素高几个数量级。
本研究发现用于治疗感染的抗生素在热稳定性和洗脱方面存在显著差异。阿米卡星表现出与妥布霉素相似的活性。美罗培南在最初7天内显示出良好的洗脱动力学和热稳定性。
阿米卡星和美罗培南作为PMMA局部给药治疗骨科感染的潜在可接受替代药物显示出药理学前景。需要进一步开展工作以确立其临床相关性和实用性。
