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Enterococcus faecalis Is Associated with Anastomotic Leak in Patients Undergoing Colorectal Surgery.

ABSTRACT: Background: Anastomotic leak is among the most dreaded complications in patients undergoing colorectal surgery. We have discovered that in rodents, collagenase-producing bacteria, particularly Enterococcus faecalis, promotes anastomotic leak by degrading healing anastomotic tissue. Yet, it is unclear if these organisms play a role in humans. Patients and Methods: Patients undergoing colorectal resection at the University of Chicago from July 2014 through June 2019 who developed a post-operative infection were stratified into infections that resulted from an anastomotic leak, a Hartmann pouch stump leak, or a deep infection without an associated staple line leak. Results: Forty-two patients had available culture data. Of these patients, 19 were found to have an anastomotic leak, 7 had a stump leak, and 16 had a deep infection that was not associated with a staple line. Enterococcus faecalis was identified in 24% of all infections and was associated with the development of anastomotic leak (p = 0.029). When the organisms were classified into their known ability to produce collagenase, 74% of patients with an anastomotic leak were colonized with collagenase-producing organisms, compared with only 28% of patients with a deep infection or stump leak (p = 0.022). Antibiotic-resistant organisms were more common in patients with anastomotic leak (p = 0.01). Conclusions: Collagenase-producing and antibiotic-resistant organisms are more prevalent in anastomotic leak infections compared with other deep or organ/space infections. This lends evidence to a bacterial driven pathogenesis of leak and suggests that targeting these organisms may be a novel strategy to reduce this complication.

SUBMITTER: Anderson DI

PROVIDER: S-EPMC8851212 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Enterococcus faecalis Is Associated with Anastomotic Leak in Patients Undergoing Colorectal Surgery.

Anderson Dana I DI Keskey Robert R Ackerman Max T MT Zaborina Olga O Hyman Neil N Alverdy John C JC Shogan Benjamin D BD

Surgical infections 20210713 10

Background: Anastomotic leak is among the most dreaded complications in patients undergoing colorectal surgery. We have discovered that in rodents, collagenase-producing bacteria, particularly Enterococcus faecalis, promotes anastomotic leak by degrading healing anastomotic tissue. Yet, it is unclear if these organisms play a role in humans. Patients and Methods: Patients undergoing colorectal resection at the University of Chicago from July 2014 through June 2 ...[more]

PMID: 34255574

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Project description:ObjectivePredicting the risk of anastomotic leak (AL) is of importance when defining the optimal surgical strategy in colorectal surgery. Our objective was to perform a systematic review of existing scores in the field.MethodsWe followed the PRISMA checklist (S1 Checklist). Medline, Cochrane Central and Embase were searched for observational studies reporting on scores predicting AL after the creation of a colorectal anastomosis. Studies reporting only validation of existing scores and/or scores based on post-operative variables were excluded. PRISMA 2020 recommendations were followed. Qualitative analysis was performed.ResultsEight hundred articles were identified. Seven hundred and ninety-one articles were excluded after title/abstract and full-text screening, leaving nine studies for analysis. Scores notably included the Colon Leakage Score, the modified Colon Leakage Score, the REAL score, www.anastomoticleak.com and the PROCOLE score. Four studies (44.4%) included more than 1.000 patients and one extracted data from existing studies (meta-analysis of risk factors). Scores included the following pre-operative variables: age (44.4%), sex (77.8%), ASA score (66.6%), BMI (33.3%), diabetes (22.2%), respiratory comorbidity (22.2%), cardiovascular comorbidity (11.1%), liver comorbidity (11.1%), weight loss (11.1%), smoking (33.3%), alcohol consumption (33.3%), steroid consumption (33.3%), neo-adjuvant treatment (44.9%), anticoagulation (11.1%), hematocrit concentration (22.2%), total proteins concentration (11.1%), white blood cell count (11.1%), albumin concentration (11.1%), distance from the anal verge (77.8%), number of hospital beds (11.1%), pre-operative bowel preparation (11.1%) and indication for surgery (11.1%). Scores included the following peri-operative variables: emergency surgery (22.2%), surgical approach (22.2%), duration of surgery (66.6%), blood loss/transfusion (55.6%), additional procedure (33.3%), operative complication (22.2%), wound contamination class (1.11%), mechanical anastomosis (1.11%) and experience of the surgeon (11.1%). Five studies (55.6%) reported the area under the curve (AUC) of the scores, and four (44.4%) included a validation set.ConclusionExisting scores are heterogeneous in the identification of pre-operative variables allowing predicting AL. A majority of scores was established from small cohorts of patients which, considering the low incidence of AL, might lead to miss potential predictors of AL. AUC is seldom reported. We recommend that new scores to predict the risk of AL in colorectal surgery to be based on large cohorts of patients, to include a validation set and to report the AUC.

Project description:BackgroundPrevious work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues.MethodsPolyphosphorylated polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA-PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed.ResultsOvernight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA-PEG20k-Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6-4800-fold (P = 0·008; 5 animals).ConclusionThese data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Clinical relevance Progress in understanding the pathogenesis of anastomotic leak continues to point to intestinal bacteria as key causative agents. The presence of pathogens such as Enterococcus faecalis that predominate on anastomotic tissues despite antibiotic use, coupled with their ability to produce collagenase, appears to alter the process of healing that leads to leakage. Further antibiotic administration may seem logical, but carries the unwanted risk of eliminating the normal microbiome, which functions competitively to exclude and suppress the virulence of pathogens such as E. faecalis. Therefore, non-antibiotic strategies that can suppress the production of collagenase by E. faecalis without affecting its growth, or potentially normal beneficial microbiota, may have unique advantages. The findings of this study demonstrate that drinking a phosphate-based polymer can achieve the goal of preventing anastomotic leak by suppressing collagenase production in E. faecalis without affecting its growth.

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Enterococcus faecalis Is Associated with Anastomotic Leak in Patients Undergoing Colorectal Surgery.

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<i>Enterococcus faecalis</i> Is Associated with Anastomotic Leak in Patients Undergoing Colorectal Surgery.

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