Yu Kristin, Song Lee, Kang Hyunwoo Paco, Kwon Hyuk-Kwon, Back Jungho, Lee Francis Y
Department of Orthopaedics and Rehabilitation, Yale University, New Haven, Connecticut, USA.
Department of Orthopaedics, Columbia University, New York, New York, USA.
Bone Joint Res. 2020 May 16;9(2):49-59. doi: 10.1302/2046-3758.92.BJR-2019-0131.R1. eCollection 2020 Feb.
To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone.
Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation.
MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent.
The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. 2020;9(2):49-59.
表征耐甲氧西林金黄色葡萄球菌（MRSA）对成骨细胞和破骨细胞的细胞内渗透情况以及MRSA在骨组织中的抗生素和去污剂敏感性。
采用延时共聚焦显微镜分析MRSA菌株USA300与原代小鼠成骨细胞和破骨细胞的相互作用。对早期和延迟抗生素治疗对细胞内和细胞外细菌集落形成及细胞死亡的影响进行定量分析。我们测试了头孢唑林、庆大霉素、万古霉素、四环素、利福平、氨苄西林以及手术准备和冲洗中使用的药物的效果。
MRSA在15至30分钟内侵入骨驻留细胞。早期（即30分钟）给予抗生素能最有效地防止其侵入。利福平与其他抗生素联合使用可增强其对MRSA诱导的细胞毒性的保护作用，并最显著地降低细胞外细菌生物负荷。含庆大霉素的化合物在降低细胞内MRSA生物负荷方面最有效。在所评估的手术准备药物中，碘伏在体外对MRSA生长的抑制作用最大。
开放性骨折的护理标准包括在受伤后的前六个小时内进行清创和使用抗生素，但未考虑细菌侵入细胞的窗口期。受伤后或切开前必须尽早给予抗生素，以防止细胞内感染。利福平可增强抗生素方案降低MRSA诱导的细胞毒性的能力。2020年；9（2）：49 - 59。
