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Page 4 of 6 Chouillard et al. Mini-invasive Surg 2021;5:9 I http://dx.doi.org/10.20517/2574-1225.2020.108
[12]
Three studies looked more closely into the incidence of CD after ileostomy closure [12-14] . Hussain et al.
prospectively evaluated 20 patients undergoing ileostomy reversal. Two stool samples were collected before
and after the procedure and tested for CD and toxins A and B. None of the patients had positive tests
preoperatively. Two of the 20 patients had asymptomatic postoperative CD colonization (10%), while one
[13]
patient developed clinical CDI with positive toxins (5%). Randall et al. retrospectively analyzed patients
who had ileostomy closure and subsequent CDI. Six (4.2%) of the 143 patients who had ileostomy reversal
[14]
developed CDI. In a retrospective large population-based analysis (2004-2008) in the US, Wilson et al.
found the incidence of CDI after ileostomy closure to be 1.6%.

There is no clear explanation yet for the high rate of CDI after ileostomy closure. Theoretically, CD could
colonize the small bowel, with many studies reporting symptomatic enteritis. Animal studies have shown
that excluded colons undergo mucosal and muscular atrophy with derangement in the intestinal immune
system. The exclusion of the colon could change the unique microbial ecosystem in the large bowel and
favor the growth of CD. When the stoma is closed, the spores could get reactivated and enter a growth
phase leading to clinical infection.

We suppose that the prophylactic antibiotics administered at the induction of anesthesia at the index
operation may have triggered the CDI in our 2 cases. Previous studies have reported that the risk of
subsequent CDI was 5.9-fold higher among patients colonized with toxigenic CD upon hospital admission
[15]
as compared to non-colonized patients . In our protocol, patients are tested for CD colonization before
all colorectal resections. Both patients in our study were negative preoperatively. Besides antibiotics as
well-known risk factors for CDI , other incriminating factors include previous hospitalization within
[16]
[17]
[15]
3 months , chemotherapy within the previous 8 weeks , or even gastric acid suppression with proton
[18]
pump inhibitors (PPIs) .
[19]
Rubio-Perez et al. reported a significant association between CDI and delayed ileostomy reversal (of
greater than 6 months), with the reported dysfunctional time ranging from 9 to 15 months. Our two
patients underwent ileostomy closure less than 2 months after the first surgery. Neither patient received
PPIs, and both had stopped their oral chemotherapy more than 3 months earlier. A meta-analysis published
in 2017 found that the incidence of CDI after ileostomy reversal was 1.8%. It also suggested that probiotics
should be considered, PPIs avoided, and rectal swabs considered in high-risk patients, and that when
[20]
possible ileostomy closure should be scheduled within 6 months .
Despite its low incidence, the clinical presentation of CDI may be indistinguishable from the usual
postoperative state. Therefore, diagnosis could be challenging. Since fulminant cases are known to occur,
clinicians must consider this condition in the differential diagnosis. Prompt evaluation is warranted in
patients undergoing ileostomy reversal who present with severe diarrhea and abdominal pain. Clinicians
should be aware of the risk factors for CDI. Systematic preoperative testing of colonization with CD should
be encouraged. We also recommend reducing the use of unwarranted antibiotics and PPIs.

Although neither of these patients required adjuvant chemotherapy, and the best timing of ileostomy
closure during or after adjuvant treatments has not been well established, one should consider early
ileostomy reversal where appropriate, even if it does not seem to completely prevent CDI. Considering the
nature of the topic and question, the highest level evidence that can potentially be achieved in this context
is from case-control studies (level 3) and meta-analysis of observational studies (level 2-3). Notably, a
meta-analysis did not see any difference in outcomes whether ileostomies were reversed during or after
[21]
adjuvant treatments . Prophylactic use of vancomycin enemas in the excluded colons prior to ileostomy
closure is an option to be further evaluated . Additionally, metronidazole should potentially be added to
[22]
the preoperative regimen when a protective ileostomy is envisioned.