although only 15% are significant enough to warrant endoscopic, radiological, or surgical
procedures. Possible manifestations include gastrointestinal bleeding, diarrhea, abdominal
pain, jaundice, nausea or vomiting, odynophagia, dysphagia, or just weight loss (166).
Hepatobiliary, peptic ulcer, and pancreatic complications are the most prevalent. Peritonitis,
intra-abdominal infections, andClostridium difficilecolitis accounted for 5% of all febrile
episodes in OLT in the ICU (9). CMV andC. difficileare the most common causes of infectious
diarrhea in SOT patients. A particular gastric lymphoma called mucosa-associated lymphoid
tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the
eradication ofHelicobacter pylori(167).
CMV may involve the whole gastrointestinal tract, although duodenum and stomach are
the most frequent sites involved (168). Infection of the upper gastrointestinal tract with CMV
used to be a major cause of morbidity in transplant patients (169). In one series 53/201 HT
patients had persistent upper gastrointestinal symptoms (abdominal pain, nausea, and
vomiting). Of these 53 patients, 16 (30.2%) had diffuse erythema or ulceration of the gastric
mucosa (14), esophagus (1), and duodenum (1) with biopsy results that were positive for CMV
on viral cultures (incidence, 8%). All patients with positive biopsy results were treated with IV
ganciclovir. Recurrence developed in 6 patients (37.5%) and required repeated therapy with
ganciclovir. None of the 16 patients died as a result of gastrointestinal CMV infection. Other
possible presentation symptoms are fever and gastrointestinal bleeding. Differential diagnosis
should include diverticulitis, intestinal ischemia, cancer, and Epstein-Barr virus (EBV)-
associated lymphoproliferative disorders. Practically all patients with gastrointestinal CMV
will have a positive PCR in blood. However, occasionally, severe intestinal CMV disease may
occur in patients with negative antigenemia, especially in patients on mycophenolate mofetil
(58). PCR is also an accurate method for the detection of CMV in the mucosa of the GI tract
(170).
The natural history of CMV disease associated with solid-organ transplantation has been
modified as a result of the widespread use of potent immunosuppressants and antiviral
prophylaxis and late severe forms are now detected (171). Hypogammaglobulinemia may also
justify severe or relapsing forms of CMV after solid-organ transplantation (172).
Clostridium difficileshould be suspected in patients who present with nosocomial or
community-acquired diarrhea. It is more common in transplant population who frequently
receive antimicrobial agents, and up to 20% to 25% of patients may experience a relapse
(173–175). Incidence ofC. difficileinfection is increasing, even taking into account improved
diagnosis and increased awareness. Most infections occur early after transplantation (174). The
most important factor in the pathogenesis of disease is exposure to antibiotics that disturb the
homeostasis of the colonic flora. Nosocomial transmission has also been described. SOT
recipients have many risk factors for developingC. difficileassociated diarrhea (CDAD):
surgery, frequent hospital admissions, antimicrobials exposure, and immunosuppression.
Most common clinical presentation is diarrhea, but clinical presentation may be
unusually severe (176,177). In a recent series, 5.7% of the kidney or pancreas transplant
recipients developed fulminant CDAD that presented with toxic megacolon, and underwent
colectomy. One of them died; the other patient survived after colectomy (178). Absence of
diarrhea is a poor prognostic factor. In these cases significant leukocytosis may be a very useful
clue. The infection may be demonstrated with a rectal swab. Occasionally, patients present
with an acute abdomen (179) or inflammatory pseudotumor (180).
Fresh stool samples should be analyzed for the presence of toxin producerC. difficile. The
reference method for diagnosis is the cell culture cytotoxin test that detects toxin B in a cellular
culture of human fibroblasts (181). Culture in specific media is also recommended since it
allows resistance study, molecular analysis of the strains, and the performance of a “second-
look” cell culture assay that enhances the potential for diagnosis (182). Toxigenic culture tests
C. difficileisolates for toxin production and has higher sensitivity and equivalent specificity
compared with the cytotoxicity assay (183).C. difficilecolitis may occur in coincidence with
CMV gastrointestinal infection (173,184).
The first step in managing diarrhea and colitis caused byC. difficileis discontinuation of
the antibiotic therapy that precipitated the disease, whenever possible. About 15% to 25% of
patients respond within a few days. Patients with severe disease should be treated with oral
Infections in Organ Transplants in Critical Care 399