Richelsoph Kelly C, Webb Nathan D, Haggard Warren O
Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152-3210, USA.
Clin Orthop Relat Res. 2007 Aug;461:68-73. doi: 10.1097/BLO.0b013e3181123889.
Daptomycin is a new antibiotic active against many resistant Gram-positive organisms and seems an appropriate candidate for local delivery for severe musculoskeletal infections. Calcium sulfate dihydrate as a delivery vehicle is readily resorbable, allows new bone formation, and can be combined with therapeutic agents. We compared the elution of daptomycin and tobramycin in calcium sulfate pellets over time and determined the dissolution rates of the pellets. Unlike other water-soluble antibiotics, daptomycin required special techniques to convert the calcium sulfate from a hemihydrate powder to a hardened dihydrate shape. The elution of daptomycin on day 1 (537 microg/mL/g) was greater than that from days 2, 3, 7, 10, 14, 21, and 28. The concentration fell to 153 microg/mL/g and 37 microg/mL/g on days 2 and 3, respectively, then remained at between 5 microg/mL/g and 7 microg/mL/g for the remainder of the study. The elution behavior of the daptomycin pellets differed from that of the tobramycin-containing pellets on days 1 through 3, but was similar from day 7 through day 28. Daptomycin-containing pellets dissolved more rapidly in vitro than tobramycin-containing pellets, although the importance of this more rapid dissolution in an in vivo situation is unknown. Using the techniques described in this paper, daptomycin can be incorporated within a calcium sulfate matrix.
达托霉素是一种对多种耐药革兰氏阳性菌有效的新型抗生素，似乎是用于严重肌肉骨骼感染局部给药的合适候选药物。二水硫酸钙作为一种给药载体易于吸收，能促进新骨形成，且可与治疗药物结合。我们比较了达托霉素和妥布霉素在硫酸钙微丸中的洗脱情况，并测定了微丸的溶解速率。与其他水溶性抗生素不同，达托霉素需要特殊技术将硫酸钙从半水合物粉末转化为硬化的二水合物形态。达托霉素在第1天的洗脱量（537微克/毫升/克）大于第2、3、7、10、14、21和28天。其浓度在第2天和第3天分别降至153微克/毫升/克和37微克/毫升/克，然后在研究的剩余时间内保持在5微克/毫升/克至7微克/毫升/克之间。达托霉素微丸在第1天至第3天的洗脱行为与含妥布霉素微丸不同，但在第7天至第28天相似。含达托霉素的微丸在体外比含妥布霉素的微丸溶解得更快，尽管这种更快溶解在体内情况下的重要性尚不清楚。使用本文所述技术，达托霉素可被掺入硫酸钙基质中。
