What Is the Role of the Gut in Wound Infections?

Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and silently travel to the wound site where they release their infectious payload. Genetic tracking of microbes at the strain level is now possible with genetic sequencing techniques and can clarify the origin of microbes that cause wound infections. An emerging field of dietary prehabilitation to modulate the microbiome before surgery is being described to improve infection-related outcomes from surgery.

The Role of the Gut Microbiome on the Development of Surgical Site Infections.

Despite advances in antisepsis techniques, surgical site infection remains the most common and most costly reason for hospital readmission after surgery. Wound infections are conventionally thought to be directly caused by wound contamination. However, despite strict adherence to surgical site infection prevention techniques and bundles, these infections continue to occur at high rates. The contaminant theory of surgical site infection fails to predict and explain most postoperative infections and still remains unproven. In this article we provide evidence that the process of surgical site infection development is far more complex than what can be explained by simple bacterial contamination and hosts' ability to clear the contaminating pathogen. We show a link between the intestinal microbiome and distant surgical site infections, even in the absence of intestinal barrier breach. We discuss the Trojan-horse mechanisms by which surgical wounds may become seeded by pathogens from within one's own body and the contingencies that need to be met for an infection to develop.

Robotic transanal minimally invasive surgery: a single institutional experience.

Robotic transanal minimally invasive surgery (R-TAMIS) is a novel and evolving technique with limited reported outcomes in the literature. Compared to the laparoscopic approach, R-TAMIS provides enhanced optics, increased degrees of motion, superior ergonomics, and easier maneuverability in the confines of the rectum. We report a single institution experience at a large quaternary referral academic medical center with R-TAMIS using the da Vinci Xi® platform. This is a retrospective review of electronic medical records at the Mayo Clinic from September 2017 to April 2020. It includes all available clinical documentations for patients undergoing R-TAMIS at our institution. Patient demographics, intraoperative data (procedure time, tumor size and distance), complications, and pathology reports were reviewed. A total of 28 patients underwent R-TAMIS. Median follow-up was 23.65 months. Sixteen patients underwent R-TAMIS for endoscopically unresectable rectal polyps, eight for rectal adenocarcinoma, two for rectal gastrointestinal stromal tumor, and two for rectal carcinoid tumor. The mean size of the lesions was 4.1 cm (range 0.2-13.8 cm). The mean location of lesions was 7.8 cm (range 0-16 cm) from the anal verge. The mean operative time was 132.5 ± 46.8 min. There was one 30-day complication, and no deaths. Twenty-three (82%) patients were discharged the day of surgery. R-TAMIS is a safe, feasible, and effective technique for the surgical treatment of a variety of rectal pathology. A hybrid technique can be used for the resecting tumors extending into the anal canal.

Hybrid Robotic Transanal Minimally Invasive Surgery Approach to Large and Low-Lying Rectal Polyps.

BACKGROUND: Transanal excision is the surgical treatment of choice for low-risk rectal pathology such as endoscopically unresectable polyps, very select early rectal cancers, as well as other benign and low-risk tumors. Robotic transanal minimally invasive surgery enhances the surgeon's ability to work in the confined space of the rectum and helps overcome the limitations of other modalities for transanal excision. Large lesions that extend to the dentate line and cannot be excised transanally impart a particular challenge. Herein, we describe a hybrid robotic transanal minimally invasive surgery approach for excising large rectal lesions that extend to the dentate line and cannot be excised by utilizing traditional transanal techniques. TECHNIQUE: With the use of a standard transanal approach, the distal margin of the lesion is marked and lifted off of the internal sphincter muscle. The dissection is continued until above the anorectal ring, and a 5.5-cm transanal platform is introduced transanally. Insufflation with an 8-mm trocar is initiated and the robotic platform is docked transanally. A 1-cm circumferential proximal margin is marked, and the excision is continued robotically until en bloc resection of the lesion is completed. The defect is closed in a transverse fashion using barbed suture. For rare cases of circumferential or nearly circumferential full-thickness defects, interrupted barbed sutures are placed equidistant, the robot is undocked, the transanal platform is removed, and a handsewn coloanal anastomosis is performed allowing complete closure of the defect. RESULTS: A hybrid robotic transanal minimally invasive surgery approach to large and low-lying rectal lesions is feasible and safe, and it has advantages over standard transanal excision including enhanced ergonomics, dexterity, and optics, as well as reduced rates of specimen fragmentation. CONCLUSION: A hybrid robotic transanal minimally invasive surgery approach allows for complete resection of very large polyps, which would otherwise be extremely challenging with standard transanal approaches. See Video at http://links.lww.com/DCR/B231.

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

Alterations of the Rectal Microbiome Are Associated with the Development of Postoperative Ileus in Patients Undergoing Colorectal Surgery.

BACKGROUND: The most common complications after colorectal surgery, postoperative ileus, surgical site infections, and anastomotic leaks continue to occur despite advances in surgical technique and enhanced recovery pathways. Preclinical studies have documented that intestinal bacteria play a role in the development of these complication, yet human data is lacking. Here we hypothesized that patients that develop ileus, surgical site infection, and/or anastomotic leak following colorectal surgery harbor a specific preoperative gut microbiome. METHODS: We performed a prospective cohort study on 101 patients undergoing colon or rectal resection at the Mayo Clinic. Rectal samples were collected preoperatively and on the ward on postoperative day two. The bacterial community from each sample was characterized by 16S rRNA and associated with the development of complications. RESULTS: The rectal microbiome collected from patients in the operating room (p = .003) and on postoperative day two (p = .001) was significantly difference in patients whom later developed postoperative ileus compared with patients that had a normal return of bowel function. Patients whom developed ileus showed increased abundance of Bacteroides spp., Parabacteroides spp., and Ruminococcus spp., bacteria that are associated with promoting intestinal inflammation. There were no differences in the microbiome in patients that developed surgical site infections or anastomotic leaks. CONCLUSIONS: In this pilot study, patients that develop postoperative ileus harbor a specific gut microbiome during the perioperative period. These findings demonstrate that the preoperative bacterial composition may predispose patients to the development of ileus and that perioperative manipulation of the gut bacteria may provide a novel method to promote normal return of bowel function.

Peritoneal dialysis catheter function and survival are not adversely affected by obesity regardless of the operative technique used.

BACKGROUND: Obesity has been considered a relative contraindication to peritoneal dialysis (PD). Surprisingly, PD catheter dysfunction rates and longevity have not been studied in the growing obese ESRD population. The aim of this study was to determine the effect of patient weight on PD catheter survival in the three insertion technique categories of advanced laparoscopy (AL), basic laparoscopy (BL), and open. METHODS: We examine retrospectively collected data on 231 consecutive PD catheter insertions at the NorthShore University HealthSystem between 2004 and 2014. Three cohorts were created based on the catheter insertion technique: open, BL using selective adhesiolysis, and AL using rectus sheath tunnel, selective omentopexy, and adhesiolysis. Primary outcomes included catheter dysfunction and catheter dysfunction-free survival for each cohort by BMI: normal weight (18.5-24.9), overweight (25-29.9), obese (≥30). Nominal variables were compared using Chi-square test, continuous variables using ANOVA or Kruskal-Wallis tests, and catheter survival was assessed using the Kaplan-Meier method with log-rank test. Statistical significance was established at 0.05. RESULTS: For the three BMI categories, there were no statistically significant differences in patient demographics. There were no statistically significant differences in catheter dysfunction or peri-operative complications by BMI category among all patients. This was also true in the AL cohort. Among all patients, similar 2-year dysfunction-free catheter survival was noted for normal weight, overweight, and obese patients (log-rank p = 0.79). This was also true across all insertion techniques: open (log-rank p = 0.87), BL (log-rank p = 0.41), AL (log-rank p = 0.43). In the obese cohort, the 2-year dysfunction-free catheter survival was 91.1% in AL, 83.5% in BL, and 65.7% in open (log-rank p = 0.58). CONCLUSION: Obesity does not increase complications or shorten dysfunction-free PD catheter survival regardless of the operative technique used. Obesity should not be considered as a relative contraindication to PD catheter placement as it confers similar technique success to normal- and overweight individuals.

Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.

OBJECTIVE: The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery. BACKGROUND: We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth. METHODS: Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration. RESULTS: PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa. CONCLUSIONS: Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.

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

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.

Collapse of the Microbiome, Emergence of the Pathobiome, and the Immunopathology of Sepsis.

The definition of sepsis has been recently modified to accommodate emerging knowledge in the field, while at the same time being recognized as challenging, if not impossible, to define. Here, we seek to clarify the current understanding of sepsis as one that has been typically framed as a disorder of inflammation to one in which the competing interests of the microbiota, pathobiota, and host immune cells lead to loss of resilience and nonresolving organ dysfunction. Here, we challenge the existence of the idea of noninfectious sepsis given that critically ill humans never exist in a germ-free state. Finally, we propose a new vision of the pathophysiology of sepsis that includes the invariable loss of the host's microbiome with the emergence of a pathobiome consisting of both "healthcare-acquired and healthcare-adapted pathobiota." Under this framework, the critically ill patient is viewed as a host colonized by pathobiota dynamically expressing emergent properties which drive, and are driven by, a pathoadaptive immune response.

Influence of nutrition therapy on the intestinal microbiome.

PURPOSE OF REVIEW: This review describes the relationship between nutritional therapies and the intestinal microbiome of critically ill patients. RECENT FINDINGS: The intestinal microbiome of the critically ill displays a near complete loss of health-promoting microbiota with overgrowth of virulent healthcare-associated pathogens. Early enteral nutrition within 24 h of admission to the ICU has been advocated in medical and surgical patients to avoid derangements of the intestinal epithelium and the microbiome associated with starvation. Contrary to previous dogma, permissive enteral underfeeding has recently been shown to have similar outcomes to full feeding in the critically ill, whereas overfeeding has been shown to be deleterious in those patients who are not malnourished at baseline. Randomized clinical trials suggest that peripheral nutrition can be used safely either as the sole or supplemental source of nutrition even during the early phases of critical care. The use of probiotics has been associated with a significant reduction in infectious complications in the critically ill without a notable mortality benefit. SUMMARY: Focus of research is shifting toward strategies that augment the intestinal environment to facilitate growth of beneficial microorganisms, strengthen colonization resistance, and maintain immune homeostasis.

Modeling Acinetobacter baumannii wound infections: The critical role of iron.

BACKGROUND: Acinetobacter baumannii has emerged as an increasingly important and successful opportunistic human pathogen due to its ability to withstand harsh environmental conditions, its characteristic virulence factors, and quick adaptability to stress. METHODS: We developed a clinically relevant murine model of A. baumannii traumatic wound infection to determine the effect of local wound environment on A. baumannii virulence. Mice underwent rectus muscle crush injury combined with ischemia created by epigastric vessel ligation, followed by A. baumannii inoculation. Reiterative experiments were performed using (1) a mutant deficient in the production of the siderophore acinetobactin, or (2) iron supplementation of the wound milieu. Mice were euthanized 7 days later, and rectus muscle analyzed for signs of clinical infection, HIF1α accumulation, bacterial abundance, and colony morphotype. To determine the effect of wound milieu on bacterial virulence, Galleria mellonella infection model was used. RESULTS: The combination of rectus muscle injury with ischemia and A. baumannii inoculation resulted in 100% incidence of clinical wound infection that was significantly higher compared with other groups (n = 15/group, p < 0.0001). The highest level of wound infection was accompanied by the highest level of A. baumannii colonization (p < 0.0001) and the highest degree of HIF1α accumulation (p < 0.05). A. baumannii strains isolated from injured/ischemic muscle with clinical infection displayed a rough morphotype and a higher degree of virulence as judged by G. mellonella killing assay as compared with smooth morphotype colonies isolated from injured muscle without clinical infection (100% vs. 60%, n = 30 Log-Rank test, p = 0.0422). Iron supplementation prevented wound infection (n = 30, p < 0.0001) and decreased HIF1α (p = 0.039643). Similar results of decrease in wound infection and HIF1α were obtained when A. baumannii wild type was replaced with its derivative mutant [INCREMENT]BasD deficient in acinetobactin production. CONCLUSION: The ability of A. baumannii to cause infections in traumatized wound relies on its ability to scavenge iron and can be prevented by iron supplementation to the wound milieu.

Laparoscopic peritoneal dialysis catheter insertion using rectus sheath tunnel and selective omentopexy significantly reduces catheter dysfunction and increases peritoneal dialysis longevity.

BACKGROUND: Success of peritoneal dialysis depends on the durability of the peritoneal dialysis catheter, which in turn depends on insertion technique. Catheter-related complications are among the main reasons for peritoneal dialysis failure. Techniques showing evidence of improved catheter function include rectus sheath tunnel, selective omentopexy, and adhesiolysis. METHODS: Single-institution retrospective review of consecutive peritoneal dialysis catheter insertions was performed between 2004 and 2014. Of 235 procedures, the open technique was utilized in 63, basic laparoscopy with selective adhesiolysis in 80, and advanced laparoscopy utilizing rectus sheath tunnel, selective omentopexy, and adhesiolysis in 92. Primary outcomes included catheter dysfunction, catheter dysfunction-free, and overall survival. RESULTS: Mechanical catheter dysfunction occurred in 4 patients (4.4%) in the advanced laparoscopy group, 14 (17.5%) in the basic laparoscopy group, and 20 (31.8%) in the open group (P < .01). The advanced laparoscopy group had the highest rate of dysfunction-free and overall catheter survival. The rectus sheath tunnel was protective independently of dysfunction free catheter survival. The rate of switch to hemodialysis also was significantly lower in the advanced laparoscopic group (P = .031). CONCLUSION: Advanced laparoscopic peritoneal dialysis catheter insertion using rectus sheath tunnel, selective omentopexy, and adhesiolysis is associated with decreased catheter dysfunction rates, improved dysfunction-free and overall catheter survival, and lowest rate of switch to hemodialysis.

The role of the microbiota in surgical recovery.

PURPOSE OF REVIEW: The purpose of this review is to highlight new research findings in the complex bidirectional crosstalk that occurs between the intestinal microbiome and the host immune system in the context of surgical recovery and outcomes. RECENT FINDINGS: Significant evidence has been generated emphasizing the central role of the intestinal microbiome on surgical outcomes such as wound healing, surgical site infections and anastomotic leak. Current preventive strategies, including the use of some parenteral antibiotics, may actually exacerbate the problem by selecting for drug-resistant pathogens. SUMMARY: A delicate balance exists between the human host and its microbial counterparts that is directly related to postsurgical healing. This balance can be easily altered in favor of the pathogen through perioperative and surgical interventions leading to intestinal dysbiosis and loss of colonization resistance. Current strategies to prevent infectious complications with the escalating use of broader and more powerful antibiotics are not an evolutionarily stable strategy. A more complete understanding of the ecological and molecular interactions of the host with its microbiome is necessary to uncover new therapeutic strategies that preserve the composition and function of the intestinal microbiome and constrain virulent pathogens through the course of surgical injury.

The Shift of an Intestinal "Microbiome" to a "Pathobiome" Governs the Course and Outcome of Sepsis Following Surgical Injury.

Sepsis following surgical injury remains a growing and worrisome problem following both emergent and elective surgery. Although early resuscitation efforts and prompt antibiotic therapy have improved outcomes in the first 24 to 48  h, late onset sepsis is now the most common cause of death in modern intensive care units. This time shift may be, in part, a result of prolonged exposure of the host to the stressors of critical illness which, over time, erode the health promoting intestinal microbiota and allow for virulent pathogens to predominate. Colonizing pathogens can then subvert the immune system and contribute to the deterioration of the host response. Here, we posit that novel approaches integrating the molecular, ecological, and evolutionary dynamics of the evolving gut microbiome/pathobiome during critical illness are needed to understand and prevent the late onset sepsis that develops following prolonged critical illness.