In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads

In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads
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DOI:
10.1128/aac.41.2.415
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发表时间:
1997-02-01
影响因子:
4.9
通讯作者:
Cobos, J
Cobos, J
中科院分区:
医学2区
文献类型:
--
作者:
Mader, JT;Calhoun, J;Cobos, J

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在清创手术后,在死骨间隙中使用抗生素浸渍的珠粒以递送局部高浓度的抗生素,将聚甲基丙烯酸甲酯(PMMA)、2,000-分子量(MW)聚乳酸(PLA)、聚(DL-丙交酯)-共乙交酯(PL:CG; 90:10、80:20和70:30)和组合2,000-MW PLA-70:30 PL:CG单独与克林霉素、妥布霉素或万古霉素混合。将珠粒置于Iml磷酸盐缓冲盐水(PBS)中并在37 ° C下孵育。每天更换PBS,并将取出的PBS样品储存在-70 ° C下,直到通过微生物纸片扩散测定法测定每个样品中的抗生素浓度。具有妥布霉素和克林霉素的不溶性PMMA珠的浓度远高于断点敏感性浓度(即,在细菌杀灭和对抗生素的抗性之间的转变点处的抗生素浓度)超过90天,但万古霉素浓度在第12天下降。所有PLA、PL:CG和2,000-MW PLA-70:30 PL:CG生物可降解珠在体外释放高浓度的所有抗生素持续治疗骨感染所需的时间段(即,4至8周),与目前临床环境中使用的PMMA珠相比,抗生素负载的PLA和PL:CG珠具有更好的抗生素洗脱和生物降解能力的优势(从而避免需要二次手术去除珠)。
Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics, Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:30 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin, Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic concentration in each sample was determined by microbiological disk diffusion assay, Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. All PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks), Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegrade (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting.