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耐甲氧西林金黄色葡萄球菌能否从肠道“悄无声息”地转移至伤口并引发术后感染?——“特洛伊木马假说”模型构建

Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the "Trojan Horse Hypothesis".

机构信息

Center for Surgical Infection Research and Therapeutics, Pritzker School of Medicine, University of Chicago, Chicago, IL.

出版信息

Ann Surg. 2018 Apr;267(4):749-758. doi: 10.1097/SLA.0000000000002173.

Abstract

OBJECTIVE

To determine whether intestinal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be the source of surgical site infections (SSIs).

BACKGROUND

We hypothesized that gut-derived MRSA may cause SSIs via mechanisms in which circulating immune cells scavenge MRSA from the gut, home to surgical wounds, and cause infection (Trojan Horse Hypothesis).

METHODS

MRSA gut colonization was achieved by disrupting the microbiota with antibiotics, imposing a period of starvation and introducing MRSA via gavage. Next, mice were subjected to a surgical injury (30% hepatectomy) and rectus muscle injury and ischemia before skin closure. All wounds were cultured before skin closure. To control for postoperative wound contamination, reiterative experiments were performed in mice in which the closed wound was painted with live MRSA for 2 consecutive postoperative days. To rule out extracellular bacteremia as a cause of wound infection, MRSA was injected intravenously in mice subjected to rectus muscle ischemia and injury.

RESULTS

All wound cultures were negative before skin closure, ruling out intraoperative contamination. Out of 40 mice, 4 (10%) developed visible abscesses. Nine mice (22.5%) had MRSA positive cultures of the rectus muscle without visible abscesses. No SSIs were observed in mice injected intravenously with MRSA. Wounds painted with MRSA after closure did not develop infections. Circulating neutrophils from mice captured by flow cytometry demonstrated MRSA in their cytoplasm.

CONCLUSIONS

Immune cells as Trojan horses carrying gut-derived MRSA may be a plausible mechanism of SSIs in the absence of direct contamination.

摘要

目的

确定耐甲氧西林金黄色葡萄球菌(MRSA)肠道定植是否可能成为手术部位感染(SSI)的来源。

背景

我们假设肠道来源的 MRSA 可能通过以下机制引起 SSI,即循环免疫细胞从肠道中清除 MRSA,归巢到手术伤口并引起感染(特洛伊木马假说)。

方法

通过抗生素破坏微生物群来实现 MRSA 肠道定植,使动物经历饥饿期,并通过灌胃引入 MRSA。然后,对小鼠进行手术损伤(30%肝切除术)和腹直肌损伤及缺血,然后关闭皮肤。在关闭皮肤之前对所有伤口进行培养。为了控制术后伤口污染,我们在已闭合的伤口连续 2 天用活 MRSA 涂抹的小鼠中重复进行实验。为了排除细胞外菌血症是导致伤口感染的原因,我们对经历腹直肌缺血和损伤的小鼠静脉注射 MRSA。

结果

所有伤口培养在皮肤闭合前均为阴性,排除了术中污染。在 40 只小鼠中,有 4 只(10%)出现可见脓肿。9 只(22.5%)没有可见脓肿的小鼠的腹直肌 MRSA 培养阳性。静脉注射 MRSA 的小鼠未观察到 SSI。闭合后用 MRSA 涂抹的伤口未发生感染。通过流式细胞术捕获的小鼠循环中性粒细胞的细胞质中显示有 MRSA。

结论

携带肠道来源的 MRSA 的免疫细胞作为特洛伊木马可能是在没有直接污染的情况下发生 SSI 的一种合理机制。

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