Diagnosis and Management of C. difficile Infection

Diagnostic Approach

The World Health Organization and the Centers for Disease Control and Prevention recommend that diagnostic testing should only be performed on diarrheal stool (≥3 unformed stools in 24 hours) from symptomatic patients, not on formed stool, as this results in false positives and unnecessary antibiotic therapy 1, 2
The American College of Gastroenterology recommends laboratory testing of diarrheal stool specimens as the primary diagnostic method, using nucleic acid amplification tests (NAAT) or two-step algorithms starting with toxin-EIA, with a sensitivity of 95.7% and specificity of 100% for perirectal swabs tested by PCR 1, 2
The Infectious Diseases Society of America suggests considering clinical context, including recent antibiotic use, hospitalization, advanced age, fever, abdominal pain, and leukocytosis, to guide testing decisions, with a positive predictive value of 100% and negative predictive value of 99.1% for perirectal swabs compared to stool specimens 1, 2

The Society of Abdominal Radiology recommends imaging (CT) showing colonic wall thickening >4mm, accordion sign, pericolonic stranding, or unexplained ascites when stool testing is not feasible, with a high degree of evidence, although this is based on a lower level of evidence from Praxis Medical Insights 3, 4
The American Society for Gastrointestinal Endoscopy states that flexible sigmoidoscopy is appropriate only for patients with high clinical suspicion and negative stool tests, or when urgent differentiation from other causes of acute colitis is needed, with a moderate level of evidence 3

The Centers for Disease Control and Prevention advise against testing formed stool as this results in false positives and unnecessary antibiotic therapy, with a high strength of evidence 1
The World Health Organization recommends against performing routine rectal exams for C. difficile diagnosis when patients can produce diarrheal stool, with a high strength of evidence 1, 2