Mechanical and oral antibiotic bowel prep should be standard before elective rectal resection

Anastomotic dehiscence is one of the most devastating and potentially life-threatening complications in colorectal surgery, its risk being highest among patients undergoing pelvic anastomoses such as ultralow anterior resections with coloanal anastomoses as compared to those undergoing more proximal anastomoses (1). Surgical tenets including creation of a tension-free anastomosis, lack of distal obstruction downstream of the anastomosis, excellent perfusion to the involved segments of intestine, adequate nutritional status of the patient, and selective use of proximal diversion, are all principles employed to help mitigate the risk of this complication (2). Preoperative bowel preparation is also an essential intervention to prevent both surgical site infections (SSIs) and anastomotic dehiscence for patients undergoing colorectal surgery. The MOBILE2 trial comparing mechanical plus oral antibiotic bowel prep (MOABP) to mechanical bowel prep (MBP) alone provides us with vital information regarding the use of bowel prep for patients specifically undergoing rectal resections (3).

Appropriate preoperative bowel prep accomplishes several objectives for patients undergoing colorectal surgery (4). Removal of gross stool allows for easier handling and manipulation of the bowel, which is especially relevant for successful completion of minimally invasive colorectal surgery. The absence of large volumes of stool within the intestine also decreases the size of the bowel. Smaller bowel caliber improves visualization during laparoscopy, facilitating the ability to complete surgeries minimally invasively, and may also allow for easier mobilization and extracorporealization of the intestines through smaller incisions during open procedures (5,6). The absence of solid fecal material within the bowel lumen allows for optimal apposition of staplers with the bowel wall, thus limiting the chance that solid objects may be interposed between the stapler and bowel which could result in imperfect staple alignment during anastomoses. It also limits the volume of peritoneal contamination in the event gross spillage occurs during an operation. Finally, an adequately prepped colon facilitates intraoperative endoscopy when necessary.

MBP in isolation has been used to cleanse the intestine prior to colorectal surgery since the early 20^th century (7,8). At that time, surgeons prescribed various preoperative diets and laxative regimens with the aim of reducing infectious complications for gastrointestinal operations (9). Mechanical preparations alone were surgical dogma during the early and mid-1900s, but this doctrine was challenged when Hughes published the results of their randomized controlled trial finding that infectious and anastomotic complications were not reduced in patients who did receive MBP as compared to those who omitted it (10). For the next three decades, a multitude of trials evaluating the efficacy of MPB alone on a number of infectious and surgical outcomes were carried out. A subsequent Cochrane Database meta-analysis and systematic review published in 2011, evaluating over 5,800 patients from 18 trials, found no statistically significant benefit regarding anastomotic dehiscence or wound complications from routine use of MBP alone in colorectal surgery (11).

Around the same time, beginning in the 1950s, reports detailing the use of antibiotic bowel preparations began to be published (5). Cohn et al. published a series of studies evaluating the microbiological impact of various antibiotic regimens on colonic flora (12-14). Then, in 1973, Nichols et al. published the results of their landmark trial and subsequent retrospective assessment in which mechanical bowel preparation was combined with oral neomycin and erythromycin preoperatively, today known as the Nichols’ prep (5,15). Using this protocol, they demonstrated a significantly reduced colonic bacterial load of both aerobic and anaerobic microbial species in the MOABP group as compared to the MBP only group, which translated clinically into a marked reduction in SSIs. Subsequently, a plethora of trials comparing various MOABP regimens to MBP only regimens in colorectal surgery ensued, repeatedly demonstrating reduced rates of infectious and anastomotic complications in the MOABP groups. This led to the publication of a review and meta-analysis of 26 trials in The New England Journal of Medicine in 1981 which concluded that given the overwhelmingly positive results associated with MOABP in regard to infectious complications for colon surgery, trials using control groups who do not receive oral antibiotic prep should no longer be performed as these control groups would not be receiving the standard of care (16). These practices are echoed in the current American Society of Colon and Rectal Surgery clinical practice guidelines, which endorse a strong recommendation for the use of MOABP prior to elective colorectal operations (4). More contemporarily, some have considered whether oral antibiotics in the absence of mechanical bowel preparations, or even solely intravenous antibiotic prophylaxis with omission of mechanical and oral antibiotic preparations, would result in equivocal SSI complications to those seen with MOABP. However, insufficient data exist to determine whether these alternative regimens are appropriate (17).

Notably, all the discussed trials and analyses combine patients undergoing surgery on their colon and/or rectum as a single group. Resultantly, these data are limited by a lack of discrimination regarding the specific operative location within the colon or rectum. The MOBILE2 trial thus fills a major knowledge gap in colorectal literature by evaluating the efficacy of preoperative bowel preparation strictly among patients undergoing elective rectal resections (3).

The trial included 565 patients who underwent elective anterior rectal resection with colorectal or coloanal anastomosis for rectal tumors ≤15 cm from the anal verge. Patients were randomized to receive either a MOABP with neomycin and metronidazole (n=277), or MBP plus placebo (n=288). All patients received the same MBP with 2 L of polyethylene glycol and 1 L of clear liquids the day before surgery, and all patients received appropriate preoperative intravenous antibiotics prior to incision. The primary outcome was the comprehensive complication index (CCI) within 30 postoperative days of surgery, which was significantly lower in the MOABP group as compared to the MPB plus placebo group. The rate of SSIs was also significantly lower in the MOABP group, which was primarily driven by a significantly lower rate of anastomotic dehiscence in this group compared to the MPB plus placebo group. Sub-group analyses demonstrated persistent lower CCI scores and rates of organ/space infections for those with low tumors, and even for those with protective stomas, in the MOABP group. Importantly, only a single case of Clostridium difficile was reported in the MOABP group.

The findings of the MOBILE2 trial are encouraging and strengthen the position that MOABP should be standard for all patients undergoing elective rectal resections. A major limitation of this trial, though, is that only a minority of patients in both groups underwent minimally invasive surgery. Furthermore, the subgroup analysis evaluating specifically those undergoing minimally invasive resections did not find a significant benefit in the MOABP group. However, given the small numbers in this subgroup analysis, one must acknowledge that the trial was not adequately powered to accurately assess this outcome. Minimally invasive colorectal surgery has repeatedly been shown to reduce postoperative complications and SSIs as compared to open surgery, and data have shown a benefit for MOABP in elective minimally invasive colorectal surgery, as well (18-20). As noted above, this is the first trial evaluating the impact of MOABP among a group of patients only undergoing rectal resections, so further trials evaluating the effects of MOABP on those specifically undergoing minimally invasive rectal resections are needed.

As the authors note, the rate of utilization of MOABP for colorectal surgery in the United States and Europe is only about 66% at best. In particular, some surgeons and centers practice variability in the administration of MOABP depending on the level of the tumor, opting for its use in patients with low tumors but not those with more proximal rectal lesions (21,22). Given the positive results of the MOBILE2 trial, all efforts should be made to implement measures which aim to improve compliance with MOABP for patients undergoing elective rectal resections. Currently, the N.N. Petrov National Medical Research Center of Oncology is evaluating whether short-term outcomes of rectal resections for cancer after MOABP are superior to rectal resections with only MBP, which will provide further insight into this clinical question (NCT04592289). At our institution, all patients undergoing elective rectal resections routinely receive MOABP unless contraindication exists, and the majority of our resections are completed minimally invasively.

As we continue into the era of precision medicine and surgery, future endeavors should aim to assess the efficacy of tailored MOABP regimens to individual patients’ unique microbiomes. Studies have shown an association between Enterococcus and clinically significant post-operative pancreatic fistulas in pancreatic resections, and similar data have been reported for colorectal anastomotic leaks, as well (23,24). Tailored preps may not only allow exceptionally pathogenic microbes to be sterilized, but might also aid in further reducing the risk of postoperative nosocomial infections and curbing the development of antibiotic resistance.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Clinical Trials Review. The article has undergone external peer review.

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