Mader J T, Calhoun J, Cobos J
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1115, USA.
Antimicrob Agents Chemother. 1997 Feb;41(2):415-8. doi: 10.1128/AAC.41.2.415.
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-70:20 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 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 biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting.
清创手术后,在死骨腔内使用含抗生素的珠子来递送高浓度的局部抗生素。将聚甲基丙烯酸甲酯(PMMA)、2000分子量(MW)的聚乳酸(PLA)、聚(DL-丙交酯)-乙交酯(PL:CG;90:10、80:20和70:30)以及2000-MW PLA-70:20 PL:CG的组合分别与克林霉素、妥布霉素或万古霉素混合。将珠子置于1 ml磷酸盐缓冲盐水(PBS)中,在37℃下孵育。每天更换PBS,取出的PBS样品储存在-70℃,直到通过微生物纸片扩散法测定每个样品中的抗生素。含妥布霉素和克林霉素的不溶性PMMA珠子在超过90天的时间里浓度远高于断点敏感浓度(即细菌杀灭与抗生素耐药性转变点处的抗生素浓度),但万古霉素浓度在第12天下降。所有PLA、PL:CG以及2000-MW PLA-70:30 PL:CG可生物降解珠子在体外治疗骨感染所需的时间段(即4至8周)内释放高浓度的所有抗生素。与目前临床使用的PMMA珠子相比,载抗生素的PLA和PL:CG珠子具有更好的抗生素洗脱优势以及可生物降解的能力(从而避免了二次手术取出珠子的需要)。