Surgical management of Clostridioides difficile colitis in adults

INTRODUCTION — Clostridioides difficile infection (CDI) is one of the most common nosocomial infections [1]. Most commonly associated with antibiotic use and disruption of the normal microbiome, CDI is generally treated with antibiotics targeted against the pathogen [2,3]. However, treatment of CDI poses several challenges, including the management of patients who develop severe, complicated, or fulminant infection. These patients manifest a severe systemic inflammatory response, which differs significantly from mild/moderate infections [4]. Fulminant C. difficile colitis only occurs in 2 to 3 percent of patients with a CDI but accounts for most of the serious CDI complications such as ileus, megacolon, colonic perforation, and death [5].

Although some patients with fulminant C. difficile colitis may respond to continued antibiotic and supportive therapy, in others, the infection will not resolve or will continue to progress, leaving a role for surgical management [6]. The mortality of patients in this population continues to be high, ranging from 20 to 85 percent, and issues surrounding the indications for surgery, timing of surgery, and choice of operative procedures continue to evolve [7].

The surgical management of C. difficile colitis will be reviewed here. The epidemiology, pathophysiology, clinical manifestations, diagnosis, and medical treatment of CDI in adults are discussed separately. (See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology" and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridioides difficile infection in adults: Treatment and prevention".) (Related Pathway(s): Clostridioides difficile infection: Treatment of adults with an initial or recurrent infection.)

WHEN TO PERFORM SURGERY? — C. difficile infection (CDI) is predominantly treated medically. Only 1 percent (range 0.2 to 7.6 percent) of all patients with CDI and 30 percent (range 2.2 to 86 percent) with severe disease will require emergency surgery [8].

Surgical therapy is generally only considered in patients with "fulminant" C. difficile colitis. Patients are classified as having fulminant infection when they have hypotension or shock, ileus, or megacolon [2]. For patients who are critically ill from C. difficile colitis, the decision for surgical management is straightforward, especially if the patient has progressed while on maximal medical therapy. However, evidence suggests that offering surgery to critically ill patients may be too late as their mortality remains high even with surgical management [9]. Thus, the timing of surgical intervention is the key for survival of patients with severe or fulminant C. difficile colitis [10,11].

We suggest early surgical consultation as well as timely and decisive operative management based on certain clinical indicators [3,12,13]. Indications and timing for obtaining surgical consultation are discussed in another topic. (See "Clostridioides difficile infection in adults: Treatment and prevention", section on 'Surgery'.)

Indications for surgery — Absolute indications for surgery in patients with C. difficile colitis include (table 1):

●Colonic perforation or full-thickness ischemia. Although fulminant C. difficile colitis can result in colonic necrosis or perforation, this is not common (about 5 percent). Although there is no direct clinical or experimental evidence, colonic necrosis is theorized to result from malperfusion of the inflamed colon, rather than directly from CDI; the former usually occurs later in the spectrum of disease following the development of abdominal compartment syndrome/intra-abdominal hypertension.

●Abdominal compartment syndrome or intra-abdominal hypertension. (See "Abdominal compartment syndrome in adults".)

●Cardiopulmonary deterioration with ongoing or escalating need for vasopressor support despite adequate fluid resuscitation. However, using hemodynamic instability as the trigger for surgery has been associated with increased mortality (relative risk 0.50, 95% CI 0.35-0.72) [9]. Thus, surgery should ideally be performed "early" (ie, before the onset of shock).

●Respiratory failure requiring intubation and mechanical ventilation.

●Worsening end organ failure, most notably acute renal failure.

●Clinical signs of peritonitis or worsening abdominal exam despite adequate medical treatment.

Certain laboratory values in the setting of CDI have been considered relative indications for surgery, also based upon associations with poor outcomes:

●White blood cell (WBC) count >50,000 cells/mL

●Serum lactate levels >5 mmol/L, which may be an indication of colonic ischemia

WHICH PROCEDURE TO PERFORM? — Several operative approaches have been advocated in the management of patients with C. difficile colitis who meet the criteria for surgical therapy as outlined before [13]. Total abdominal colectomy used to be the standard procedure and remains the procedure of choice for patients with colonic perforation, necrosis, or abdominal compartment syndrome. For others, diverting loop ileostomy/colonic lavage is an alternative that has been associated with decreased mortality in limited studies. Partial or segmental colectomy is no longer performed due to a higher reoperative and mortality rate.

Operative findings — At laparotomy or laparoscopy, the most common operative findings are a thickened and edematous colon and ascites. The colon is often quite bland or unremarkable in appearance from the serosal surface, but this should not deter further surgical management or resection.

One should seek evidence of colonic perforation or necrosis as, although relatively uncommon (about 5 percent of cases), these findings mandate colectomy. Additionally, signs of abdominal compartment syndrome should be noted as its presence will dictate surgical approach (algorithm 1).

Choice of operation — For patients with abdominal compartment syndrome as a complication of C. difficile colitis, we suggest open total abdominal colectomy with end ileostomy rather than another procedure (algorithm 1) [6]. After the colon is removed, the abdominal compartment syndrome usually resolves, and the patient's abdominal fascia can be closed. By contrast, colonic preservation using diverting loop ileostomy/colonic lavage would mandate leaving an open abdomen and may complicate the care of the patient. It is therefore not recommended.

Open total abdominal colectomy with end ileostomy is also indicated when there is evidence of colonic perforation or necrosis (algorithm 1). In such patients, we suggest a total abdominal colectomy rather than a segmental resection that only removes the perforated/necrotic portion of the colon because segmental colectomy in the context of fulminant C. difficile colitis has been associated with a higher mortality rate than total colectomy (100 versus 14 percent) [14].

For patients without abdominal compartment syndrome or colonic perforation/necrosis, there is no clear superiority of total abdominal colectomy versus diverting loop ileostomy/colonic lavage based on limited studies [15,16]. The surgeon can choose a procedure based on their own experience and the experience of the operating room with colonic lavage. Those choosing to perform a diverting loop ileostomy should be prepared to convert to total abdominal colectomy based on intraoperative or postoperative findings (eg, abdominal compartment syndrome) (algorithm 1).

Arguments for diverting loop ileostomy/colonic lavage include the smaller magnitude of the operation, which can often be performed via a minimally invasive approach. Additionally, a diverting ileostomy is more likely to be reversed than an end ileostomy (79 versus 19 percent by six months [15]), leaving less impact on the patient's functional outcomes, including fecal continence. Arguments against this approach include that the lack of resection leaves the inflamed colon in place, which can continue to drive systemic inflammation and critical illness. Indeed, clinical resolution of critical illness is often slower without resection, and the clinical condition may continue to wax and wane for several days, making practitioners uneasy about whether the surgical therapy has achieved its goal. Others argue that recurrent CDI is also more likely without resection; however, the rate of this is not known.

There have been no randomized trials comparing any surgical therapies for C. difficile colitis. In the original series published in 2011, all (42) patients diagnosed with fulminant C. difficile colitis at a single center over an 18 month period underwent diverting loop ileostomy/colonic lavage; the authors were not selective in offering this therapy [15]. The main outcome, mortality, was 19 percent following diverting loop ileostomy versus 50 percent following total colectomy in historical controls at the same center.

A subsequent retrospective multicenter study collected data from 10 centers comparing the two approaches [16]. Although there were differences in age, sex, vasopressor requirement, renal failure, respiratory failure, and APACHE score between the two cohorts in this analysis, the adjusted mortality was significantly lower in the diverting loop ileostomy group compared with the total colectomy group (17.2 versus 39.7 percent).

Another study using data from the National Inpatient Sample database found that the annual proportion of patients undergoing only loop ileostomy increased from 11 percent in 2011 to 25 percent in 2015 [17]. Loop ileostomy was associated with a similar mortality rate (26 versus 31 percent) but a slightly higher complication rate compared with total colectomy. A greater proportion of loop ileostomies were performed within the first day of hospitalization than that of total colectomies (23 versus 12 percent).

A 2020 systematic review and meta-analysis of five observational studies associated loop ileostomy with similar mortality (26 versus 31 percent) but fewer surgical site infections compared with total colectomy [18]. A second meta-analysis showed that 76 to 100 percent of patients undergoing loop ileostomy preserved their colon, and stoma reversal was also more likely after loop ileostomy than after total abdominal colectomy [19].

HOW TO PERFORM THE SURGERY? — Total abdominal colectomy is a standard general surgical operation; the only variation is whether to preserve or resect the intra-abdominal portion of the upper rectum. Segmental or partial colectomy should not be performed for fulminant C. difficile colitis. Diverting loop ileostomy with colonic lavage is a relatively new procedure; the operative steps are described in detail and illustrated below. (See 'Diverting loop ileostomy with colonic lavage' below.)

Subtotal or total abdominal colectomy — Near-complete removal of the intra-abdominal colon (sparing the rectum) is the most definitive surgical management for fulminant C. difficile colitis [6,14,20-26]. This usually involves a laparotomy; division of the terminal ileum with resection of the entire colon; division of the colon at the rectosigmoid junction, leaving a blind, closed-off pouch of rectum in the abdomen; and creation of an end ileostomy. Surgical anastomosis is not advocated in this setting.

The length of rectum that is resected has been debated. No data exist, so the decision is left to the surgeon's discretion. Advocates for resection of the intra-abdominal portion of the rectum (ie, total abdominal colectomy) argue that this more effectively treats the critically ill patient by "debulking" most of the inflamed and unhealthy colon that is driving the systemic illness. Advocates for leaving the intra-abdominal rectum or even a portion of the sigmoid (ie, subtotal colectomy) argue that possible future reversal of the ileostomy and restoration of gastrointestinal continuity will result in improved functional outcome, fecal continence, and quality of life compared with resecting more rectum. Concerns about the infection in the residual rectal pouch have been addressed by leaving a rectal tube via the anus and delivering postoperative low-volume vancomycin flushes to treat the C. difficile infection in this segment of defunctionalized bowel [27]. Either way, the point of distal resection that is chosen must remain well vascularized after resection of the colonic mesentery and must be closed securely without dehiscence of the staple line or suture closure.

Segmental or partial resection of the colon, either of isolated segments of necrosis or perforation, or segments that appear to be more severely inflamed than others from the serosal inspection, has been performed in the past. Usually this involved a segmental resection (eg, right hemicolectomy or sigmoid resection) with creation of an end ostomy of the proximal segment, with or without a mucous fistula of the distal segment of bowel. Segmental resection strategies are generally not advocated, as C. difficile colitis is a mucosal-based infection, the extent of which is not well estimated from the serosal inspection of bowel, and the bulk of infected colon left behind may continue to drive critical illness.

Comparisons of segmental resection to total abdominal colectomies have been limited to single-center series but generally favor total abdominal colectomies [13,14]. A retrospective database study reported that 21 percent of 733 colectomies performed from 2007 to 2015 in patients with a primary diagnosis of C. difficile colitis were partial colectomies [28]. Although partial and total colectomies had similar mortality and complication rates by logistic regression analysis in this study, such analysis did not include information about either the severity of the C. difficile colitis or the extent of the partial colectomies. The definition of partial colectomy is not clear and likely involved resection of most of the intra-abdominal colon.

Diverting loop ileostomy with colonic lavage — In 2011, a single-center experience in 42 patients using a nonresection approach for patients with fulminant C. difficile colitis was published [15]. Since then, many surgeons have adopted this procedure. This approach involves operative exploration of the abdomen to first exclude colonic perforation and necrosis, followed by creation of a loop ileostomy to facilitate intraoperative colonic lavage with polyethylene glycol and postoperative colonic flushes with vancomycin. This procedure is often performed laparoscopically (eg, in 83 percent of patients in the original series). However, laparoscopy may not be possible, due to adhesions or massive bowel distention in the context of ileus or megacolon.

The steps of this procedure are described below and depicted in this figure (figure 1) [15]:

●A loop diverting ileostomy is performed approximately 20 to 40 cm proximal to the ileocecal valve, depending on the patient's anatomy of the terminal ileum.

●A large urinary catheter (26 to 30 French) is inserted into the efferent limb of the ileostomy, extending toward the colon, and the balloon is inflated to 10 cc. It is not necessary for the catheter to be placed through the ileocecal valve and into the cecum, but the catheter balloon must be inflated below the fascia.

●A rectal tube is placed via the anus. After the operation, the same rectal tube is left in place and used to collect vancomycin flushes.

●Eight liters of polyethylene glycol/balanced salt (PEG) solution are prepared in the same manner as for bowel preparation before colonoscopy. The PEG solution is warmed to approximately 38.6 degrees Celsius either by using warm water to reconstitute the solution or by using a fluid warmer. The eight liters of warm PEG solution are instilled into the colon via the catheter in the ileostomy and collected via the rectal tube. Irrigation can be facilitated by pouring the PEG solution into a reservoir with tubing connected to the urinary catheter and using gravity by holding the reservoir 50 to 100 cm above the patient. A urinary collection bag can be inverted and opened on one end to act as a funnel to accomplish this portion of the operation.

●An intraperitoneal drain is left to manage ascites.

●Postoperatively, we prefer to remove the urinary catheter from the ileostomy to avoid bowel necrosis and other complications from a ballooned catheter. We usually place a Malecot-type catheter into the ileostomy to deliver vancomycin flushes (500 mg in 500 mL of Lactated Ringer solution) three times a day for 7 to 10 days.

COMPLICATIONS — Although there are limited data, one would expect total abdominal colectomy via an open approach to have a higher rate of wound complications and subsequent hernias compared with diverting loop ileostomy performed via a minimally invasive approach. One would also expect a higher rate of pulmonary complications such as postoperative pneumonia with laparotomy due to its effects on ventilation and pulmonary toilet. Both operative approaches involve the creation of an ileostomy, and complications of fluid and electrolyte losses need to be managed appropriately. (See "Ileostomy or colostomy care and complications", section on 'Ileostomy patients'.)

Procedure-specific complications unique for diverting loop ileostomy include:

●Some surgeons have reported difficulties with intraoperative irrigation through the ileostomy; however, this only occurs when the ileostomy is created too close to a terminal ileum that is fixed in the retroperitoneum and is kinked off at this point of fixation. As mentioned above, knowing the correct orientation of the ileum and which limb to irrigate is also essential. (See 'Diverting loop ileostomy with colonic lavage' above.)

●Malecot catheter migration into the ileostomy and colon has been reported. This can be prevented by placement of a three-way stopcock on the end that is too big to go into the ileostomy.

●Patients without resection can develop subsequent abdominal compartment syndrome, particularly if their clinical course is complicated by low-output renal failure and continued ascites formation. This is rare (about 5 percent) and usually occurs within 48 hours. This risk can be mitigated by leaving an intraperitoneal drain to manage ascites.

LONG-TERM MANAGEMENT — The initial management of patients following either surgical approach involves ileostomy care and fluid management. Restoration of gastrointestinal continuity (ileostomy reversal) can be pursued in patients who survive the initial infection and can tolerate a subsequent operation. In general, such patients should have returned to their preinfection state of health and have no comorbidities that would preclude a second procedure. In the original single-center series, patients who underwent loop ileostomy were substantially more likely to have restoration of gastrointestinal continuity than historic controls at the same center who underwent total colectomy (50 versus 19 percent) [15]. This is likely secondary to diverting loop ileostomy reversal being a smaller-magnitude operation and the likelihood of a better functional outcome with preservation of the colon.

The risk of recurrent C. difficile infection (CDI) following ileostomy reversal is specific to diverting loop ileostomy/colonic lavage. This has been reported in several cases [29]. Routine testing for CDI is not indicated. Although there are no published studies, the risk of recurrent CDI may be minimized by avoiding perioperative systemic antibiotics and performing ileostomy irrigation with vancomycin at the time of ileostomy reversal. If an active program is available at the facility, fecal microbiota therapy into the ileostomy and colon to restore a healthy colonic microbiome may also be considered. (See "Fecal microbiota transplantation for treatment of Clostridioides difficile infection".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Clostridioides difficile infection".)

SUMMARY AND RECOMMENDATIONS

●Fulminant C. difficile colitis – Although Clostridioides difficile infection (CDI) is one of the most common nosocomial infections, most patients with CDI are treated medically. Surgical therapy is generally only required in patients with fulminant C. difficile colitis. Fulminant C. difficile colitis only occurs in 2 to 3 percent of patients with a CDI but accounts for most of the serious CDI complications such as ileus, megacolon, colonic perforation, and death. (See 'Introduction' above and "Clostridioides difficile infection in adults: Treatment and prevention".)

●Surgical management – Operative management is indicated for patients with C. difficile colitis causing abdominal compartment syndrome, colonic perforation, colonic necrosis, ongoing or worsening sepsis with critical illness, or clinical deterioration despite appropriate medical therapy. Other relative indications for operative management are listed in this table (table 1). (See 'Indications for surgery' above.)

•Total abdominal colectomy – For patients with C. difficile colitis causing colonic perforation, necrosis, or abdominal compartment syndrome, we suggest total abdominal colectomy with end ileostomy rather than other surgical approaches (algorithm 1) (Grade 2C). Total abdominal colectomy is the most definitive surgical management of fulminant C. difficile colitis. Whether to resect or preserve the intra-abdominal portion of the upper rectum is left to the surgeon's discretion due to a lack of data. (See 'Which procedure to perform?' above and 'Subtotal or total abdominal colectomy' above.)

•Diverting loop ileostomy – For patients requiring operative management for C. difficile colitis but not having colonic perforation, necrosis, or abdominal compartment syndrome, surgeons may choose to perform either a total abdominal colectomy with end ileostomy or a diverting loop ileostomy/colonic lavage (algorithm 1). Diverting loop ileostomy has been associated with decreased mortality and a higher ileostomy reversal rate in nonrandomized studies but may drive a slower clinical response than total abdominal colectomy. Some of the complications and long-term outcomes are unique to each surgical approach. (See 'Which procedure to perform?' above and 'Diverting loop ileostomy with colonic lavage' above and 'Complications' above.)

The steps of diverting loop ileostomy/colonic lavage, a relatively new procedure, are described and depicted in this figure (figure 1). (See 'Diverting loop ileostomy with colonic lavage' above.)