Diagnostic Yields in Solid Organ Transplant Recipients Admitted With Diarrhea

(See the Editorial Commentary by Polage on pages 738–40.) Diarrhea in solid organ transplant (SOT) recipients has been estimated to occur in 22%–52% of patients [1–4]. At one center, gastrointestinal complaints accounted for 31% of presentations to their emergency department with an associated risk of hospitalization [5]. Furthermore, posttransplant diarrhea is associated with allograft loss and increased mortality [2, 6, 7]. The impact of diarrhea on immunosuppressive therapy may, in part, explain this association. Gastrointestinal distress is a recognized side effect of mycophenolate mofetil (MMF) and mycophenolic acid (MPA), which increase tacrolimus exposure [8]. Resulting reductions in immunosuppression increase the risk of acute rejection and ultimately graft failure [9–11]. Despite its significance, the epidemiology of diarrhea in transplant recipients is poorly defined. Previously, infectious causes of diarrhea in general accounted for 13%–19% of diarrheal episodes [2, 6]. The Diarrhea Diagnosis Aid and Clinical Treatment study prospectively investigated the etiology and management of diarrhea in renal transplant recipients and identified a specific infectious etiology in 30 of 108 (28%) patients, with Campylobacter jejuni enteritis and cytomegalovirus (CMV) colitis being the most common [1]. Later studies have found that Clostridium difficile colitis is frequent, but its incidence relative to other pathogens and noninfectious etiologies has not been compared [12–15]. Recommendations for the diagnostic evaluation and management of posttransplant diarrhea are based largely on expert opinion and generally include initial stool culture, stool C. difficile assessment, and blood CMV quantitative viral load, if necessary to be followed by consideration of empiric reduction in immunosuppression, and thereafter colonoscopy [1, 16–18]. Recommendations for additional testing are quite variable and may include fecal testing for leukocytes (or lactoferrin), ova and parasites, Cystoisospora (Isospora) and Cyclospora assessments, Giardia and Cryptosporidium antigen screen or enzyme immunoassay (EIA), and norovirus detection by polymerase chain reaction (PCR). SOT recipients are at increased risk of atypical and typical infections leading to diarrhea, but it is unclear that this immunocompromised state necessarily translates to an increased incidence of all possible etiologies of diarrhea, especially with consideration of endemic and geographic exposures. There may be more optimized testing strategies, for which evidence is required. We hypothesized that the majority of SOT recipients hospitalized with diarrheal illness were attributable to a few etiologies, predominantly C. difficile and norovirus, and that the yield for other studies is low.