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Determination of the Elution Capacity of Dalbavancin in Bone Cements: New Alternative for the Treatment of Biofilm-Related Peri-Prosthetic Joint Infections Based on an In Vitro Study
Antibiotics ( IF 4.3 ) Pub Date : 2022-09-23 , DOI: 10.3390/antibiotics11101300
Mar Sánchez-Somolinos 1 , Marta Díaz-Navarro 1, 2 , Antonio Benjumea 3 , Marta Tormo 4 , José Matas 3 , Javier Vaquero 2, 3, 5 , Patricia Muñoz 2, 3, 5, 6 , Pablo Sanz-Ruíz 2, 3, 5 , María Guembe 1, 2
Affiliation  

Antibiotic-loaded bone cement is the most widely used approach for the treatment of biofilm-induced septic sequelae in orthopedic surgery. Dalbavancin is a lipoglycopeptide that acts against Gram-positive bacteria and has a long half-life, so we aimed to assess whether it could be a new alternative drug in antibiotic-loaded bone cement for the treatment of periprosthetic joint infections. We assessed the elution capacity of dalbavancin and compared it with that of vancomycin in bone cement. Palacos®R (Heraeus Medical GmbH, Wehrheim, Germany) bone cement was manually mixed with each of the antibiotics studied at 2.5% and 5%. Three cylinders were obtained from each of the mixtures; these were weighed and incubated in 5 mL phosphate-buffered saline at 37°C under shaking for 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 168 h, and 336 h. PBS was replenished at each time point. The samples were analyzed using high-performance liquid chromatography (vancomycin) and mass cytometry (dalbavancin). Elution was higher than the minimum inhibitory concentration (MIC)90 for both antibiotics after 14 days of study. The release of vancomycin at 14 days was higher than of dalbavancin at each concentration tested (p = 0.05, both). However, the cumulative release of 5% dalbavancin was similar to that of 2.5% vancomycin (p = 0.513). The elution capacity of dalbavancin reached a cumulative concentration similar to that of vancomycin. Moreover, considering that the MIC90 of dalbavancin is one third that of vancomycin (0.06 mg/L and 2 mg/L, respectively) and given the long half-life of dalbavancin, it may be a new alternative for the treatment of biofilm-related periprosthetic infections when loaded in bone cement.

中文翻译:

测定骨水泥中达巴万星的洗脱能力:基于体外研究的生物膜相关假体周围关节感染治疗的新选择

载抗生素骨水泥是骨科手术中治疗生物膜引起的脓毒性后遗症最广泛使用的方法。达巴万星是一种对抗革兰氏阳性菌的脂糖肽,具有较长的半衰期,因此我们旨在评估它是否可以成为一种新的替代药物,用于治疗假体周围感染的抗生素骨水泥。我们评估了达巴万星的洗脱能力,并将其与万古霉素在骨水泥中的洗脱能力进行了比较。帕拉科斯®R (Heraeus Medical GmbH, Wehrheim, Germany) 骨水泥与每种研究的抗生素手动混合,浓度分别为 2.5% 和 5%。从每种混合物中获得三个圆柱体;将它们称重并在 37°C 下在 5 mL 磷酸盐缓冲盐水中振荡培养 1 小时、2 小时、4 小时、8 小时、24 小时、48 小时、168 小时和 336 小时。在每个时间点补充 PBS。使用高效液相色谱法(万古霉素)和质谱流式细胞仪(达巴万星)分析样品。研究 14 天后,两种抗生素的洗脱均高于最低抑菌浓度 (MIC)90。在每个测试浓度下,万古霉素在 14 天的释放均高于达巴万星(p = 0.05,两者)。然而,5% 达巴万星的累积释放量与 2.5% 万古霉素相似(p= 0.513)。达巴万星的洗脱能力达到了与万古霉素相似的累积浓度。此外,考虑到达巴万星的 MIC90 是万古霉素的三分之一(分别为 0.06 mg/L 和 2 mg/L),并且考虑到达巴万星的长半衰期,它可能是治疗生物膜相关疾病的新选择。装在骨水泥中时的假体周围感染。
更新日期:2022-09-23
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