In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice
In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice
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DOI：
10.1128/aac.01003-12
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发表时间：
2013-02-01
影响因子：
4.9
通讯作者：
Miller, Lloyd S.
中科院分区：
文献类型：
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作者：
Guo, Yi;Ramos, Romela Irene;Miller, Lloyd S.
社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)经常引起皮肤和软组织感染，包括脓疱病、蜂窝织炎、毛囊炎以及感染的伤口和溃疡。简单的CA-MRSA皮肤感染通常在门诊环境下通过口服和局部抗生素和/或切开引流来治疗，而复杂的皮肤感染通常需要住院、静脉注射抗生素，有时还需要手术。本研究的目的是建立CA-MRSA伤口感染的小鼠模型，以比较常用的全身和局部抗生素的疗效。将一株生物发光的USA300 CA-MRSA菌株接种到小鼠背部全层手术刀创面，采用数码摄影/图像分析和体内生物发光成像技术检测创面愈合情况和细菌载量。皮下注射万古霉素、达托霉素和利奈唑胺类似地减少了皮损大小和细菌负荷。口服利奈唑胺、克林霉素和多西环素均可减少病变大小和细菌负荷。口服甲氧苄氨嘧啶-磺胺甲恶唑可减少细菌负荷，但不能缩小病灶大小。外用莫匹罗星软膏和瑞帕米林软膏都能减少细菌负担。然而，用于瑞帕帕蛋白的凡士林载体软膏，而不是用于莫匹罗星的聚乙二醇微载体软膏，促进了伤口的愈合，最初增加了细菌负担。最后，在2型糖尿病小鼠中，与万古霉素相比，皮下注射利奈唑胺和达托霉素的疗效最快。综上所述，这种利用体内生物发光成像监测细菌负荷的CA-MRSA伤口感染小鼠模型，代表了一种评估全身和局部抗菌药物临床前体内疗效的替代方法。
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.