*Purpose: Clostridium difficile infection (CDI) is the most common healthcare-associated infection in the United States. One out of 8 recipients who undergo transplantation with more than 1 organ will develop CDI. Little is known on the impact of CDI on multivisceral transplant (MVT). To our knowledge, there is no reported association between CDI and rejection in the literature, and this will be the first report of one.

*Methods: Our case series was approved by our university’s Institutional Review Board. We describe our experience with 4 pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal acute cellular rejection (ACR).

*Results: Our patients were males aged 2 to 5 years old. Case 1 had severe pseudomembranous colitis (see fig. 1) and was started on CDI treatment. Colonoscopy 5 days later showed significantly improved mucosa, but Grade 1 ACR of transplant terminal ileum and colon on biopsy. No treatment for rejection was given. His repeat endoscopy 6 days later showed resolution of his rejection. Case 2 had Grade 1 ACR at the colonic anastomotic site 6 days after diagnosis of CDI. No treatment for rejection was given. He clinically improved on CDI treatment alone and there was no rejection on his next set of biopsies 3 months later. Case 3 had Grade 1 ACR of transplant duodenum 2 days after diagnosis of CDI. No treatment for rejection was given. His endoscopy 2 weeks after CDI treatment showed resolution of his rejection. Case 4 had total aganglionosis and in the first 2 years post-transplant he had 6 admissions for recurrent CDI, three of which resulted in septic shock. He had removal of remaining native colon and a subsequent decreased frequency and severity of CDI. Biopsies from the first, third and fourth episodes showed no intestinal rejection.

*Conclusions: Case 1, 2 and 3 all had biopsy findings of mild ACR during episodes of CDI, and treatment of the CDI (without any treatment for rejection) resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over-suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild ACR is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided. It may be prudent to avoid decreasing immunosuppression during active CDI until studies are done to prove that CDI does not induce rejection.

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