A mouse model of post-arthroplasty Staphylococcus aureus joint infection to evaluate in vivo the efficacy of antimicrobial implant coatings.
A mouse model of post-arthroplasty Staphylococcus aureus joint infection to evaluate in vivo the efficacy of antimicrobial implant coatings.
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DOI：
10.1371/journal.pone.0012580
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发表时间：
2010-09-07
期刊：
影响因子：
3.7
通讯作者：
Miller LS
中科院分区：
文献类型：
--
作者：
Bernthal NM;Stavrakis AI;Billi F;Cho JS;Kremen TJ;Simon SI;Cheung AL;Finerman GA;Lieberman JR;Adams JS;Miller LS
关节置换术后感染是全关节置换术的一种毁灭性并发症，导致多次再次手术、长期使用抗生素、长期残疾和更差的临床结局。由于到2030年，美国每年的关节成形术数量将超过380万例，预计关节成形术后感染的数量将增加到每年超过266，000例。这些感染的治疗将耗尽医疗资源，并大大增加医疗成本。为了评价针对关节成形术后感染的新型预防性治疗策略，开发了一种小鼠模型，其中将生物发光金黄色葡萄球菌菌株接种到含有骨科植入物的膝关节中，并使用先进的体内成像来实时测量细菌负荷。接种5×103和5×104 CFU的小鼠出现细菌计数增加，患腿明显肿胀，与急性关节感染一致。相比之下，接种5×102 CFU的小鼠发生了低度感染，类似于更慢性的感染。离体细菌计数与LysEGFP小鼠的体内生物发光信号和EGFP-中性粒细胞荧光高度相关，用于测量感染诱导的炎症。此外，在术后第7天和第14天通过变压扫描电子显微镜（VP-SEM）观察植入物上的生物膜形成。使用该模型，米诺环素/利福平浸渍的生物可吸收聚合物植入物涂层在减少感染、减少炎症和防止生物膜形成方面是有效的。总之，这种小鼠模型可能代表了一种替代的临床前筛选工具，用于在大型动物和人类受试者中进行研究之前评估新的体内治疗策略。此外，本研究中评价的抗菌聚合物植入物涂层在临床上有效，表明该策略作为治疗干预措施对抗关节置换术后感染的潜力。
Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs. To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5×103 and 5×104 CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5×102 CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation. Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections.
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影响因子：
5.3
作者：
Bozic, Kevin J.;Kurtz, Steven M.;Berry, Daniel J.
通讯作者：
Berry, Daniel J.
DOI：
10.1002/jbm.b.31158
发表时间：
2009-01-01
影响因子：
3.4
作者：
Engelsman, Anton F.;van der Mei, Henny C.;van Dam, Gooitzen M.
通讯作者：
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影响因子：
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作者：
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Parvizi, Javad
DOI：
10.2106/00004623-198365030-00013
发表时间：
1983-01-01
影响因子：
5.3
作者：
FITZGERALD, RH
通讯作者：
FITZGERALD, RH
影响因子：
3.5
作者：
Diwanji, Sanket R.;Kong, Il Kyu;Yoon, Taek Rim
通讯作者：
Yoon, Taek Rim