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

Krezalek, Monika A. MD; Hyoju, Sanjiv MD; Zaborin, Alexander PhD; Okafor, Emeka MS; Chandrasekar, Laxmi MD; Bindokas, Vitas PhD; Guyton, Kristina MD; Montgomery, Christopher P. MD; Daum, Robert S. MD; Zaborina, Olga PhD; Boyle-Vavra, Susan PhD; Alverdy, John C. MD, FACS

doi: 10.1097/SLA.0000000000002173
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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.

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

Reprints: John C. Alverdy, MD, FACS, Professor of Surgery, Center for Surgical Infection Research and Therapeutics, Pritzker School of Medicine, University of Chicago, 5841 S Maryland MC6090, Chicago, IL 60637. E-mail: jalverdy@surgery.bsd.uchicago.edu.

The study was supported by the University of Chicago CTSA-ITM Core Subsidies Grant 2015 and NIH grant 5R01GM062344-15 (J.C.A.).

This study was presented in part at the Annual Scientific meeting of the Surgical Infection Society 2016 at which it received the Joseph Susman Memorial Award for the best oral presentation of the meeting.

The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.

This work was prepared while Susan Boyle-Vavra was employed at the University of Chicago. She is currently working at the National Institutes of Health. The other authors report no conflicts of interest.

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