Local Release of Antibiotics for Surgical Site Infection Management Using High-Purity Calcium Sulfate: An In Vitro Elution Study

Local Release of Antibiotics for Surgical Site Infection Management Using High-Purity Calcium Sulfate: An In Vitro Elution Study
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DOI:
10.1089/sur.2013.162
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发表时间:
2015-02-01
影响因子:
2
通讯作者:
Michell, Stephen
Michell, Stephen
中科院分区:
医学4区
文献类型:
--
作者:
Aiken, Sean S.;Cooper, John J.;Michell, Stephen

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背景资料:本研究的目的是表征从药用级硫酸钙珠洗脱四种抗生素,并显示洗脱的抗生素保留effictiveness.Methods:硫酸钙与庆大霉素,妥布霉素,万古霉素,或利福平(比例:20克硫酸钙,240毫克,500毫克,900毫克,和600毫克的抗生素,分别)。在37 ℃下,将3克珠浸入4 mL无菌磷酸盐缓冲盐水(PBS)中。在每个时间点(4、8、24 h; 2、7、14、28、42 d),取出洗脱液用于液相色谱-质谱分析。采用改良Kirby-Bauer纸片扩散法检测抗生素与硫酸钙微球联合使用42 d后的抗菌效果。在第一个时间点,庆大霉素和妥布霉素均洗脱至约10,000 mcg/mL的峰浓度。对于利福平,峰浓度出现在24 h,而对于万古霉素,峰浓度出现在48 h。在42个研究日的整个跨度内,洗脱浓度超过常见假体周围关节感染病原体的最低抑制浓度。质谱法证实,当从硫酸钙载体洗脱时,所有抗生素均未发生变化。在37 ° C下与硫酸钙组合42天后,抗菌功效未发生改变。结论:药用级硫酸钙具有在临床上有意义的时间段内靶向局部释放妥布霉素、庆大霉素、万古霉素和利福平的潜力。
Background: The aim of this study was to characterize the elution of four antibiotics from pharmaceutical-grade calcium sulfate beads and show that the eluted antibiotics retained efficacy.Methods: Calcium sulfate was combined with gentamicin, tobramycin, vancomycin, or rifampicin (ratio: 20 g of calcium sulfate, to 240 mg, 500 mg, 900 mg, and 600 mg of antibiotic, respectively). Three grams of beads were immersed in 4 mL of sterile phosphate-buffered saline (PBS) at 37 degrees C. At each time point (4, 8, 24 h; 2, 7, 14, 28, 42 d), eluates were removed for analysis by liquid chromatography-mass spectrometry. The antimicrobial efficacy of antibiotics combined with calcium sulfate beads after 42 d was tested by a modified Kirby-Bauer disc diffusion assay.Results: All samples showed a generally exponential decay in the eluted antibiotic concentration. At the first time point, both gentamicin and tobramycin had eluted to a peak concentration of approximately 10,000 mcg/mL. For rifampicin, the peak concentration occurred at 24 h, whereas for vancomycin, it occurred at 48 h. The eluted concentrations exceeded the minimum inhibitory concentration for common periprosthetic joint infection pathogens for the entire span of the 42 study days. Mass spectrometry confirmed all antibiotics were unchanged when eluted from the calcium sulfate carrier. Antimicrobial efficacy was unaltered after 42 d in combination with calcium sulfate at 37 degrees C.Conclusions: Pharmaceutical-grade calcium sulfate has the potential for targeted local release of tobramycin, gentamicin, vancomycin, and rifampicin over a clinically meaningful time period.