What is the diagnostic and treatment approach for C. difficile infection in a patient without diarrhea but with ileus or toxic megacolon, abdominal pain, fever, leukocytosis, recent broad‑spectrum antibiotic exposure, and colonic wall thickening on imaging?

C. difficile Colitis Without Diarrhea

C. difficile infection can present with ileus or toxic megacolon in the absence of diarrhea, and this presentation requires immediate aggressive treatment with IV metronidazole plus intracolonic and/or nasogastric vancomycin, with early surgical consultation for colectomy if the patient deteriorates. 1

Diagnostic Approach

Recognize This Atypical Presentation

• C. difficile infection without diarrhea is a well-documented and potentially lethal presentation, particularly when ileus or toxic megacolon develops. 2, 3
• The ESCMID guidelines explicitly define CDI as including ileus or toxic megacolon even without diarrhea, as long as there is evidence of toxin-producing C. difficile in stools and no other cause of symptoms. 1, 4
• Recent case series demonstrate that patients can present with abdominal distention, constipation, or minimal bowel movements rather than diarrhea, with rapid progression to toxic megacolon. 3

Clinical Criteria for Diagnosis

The diagnosis is established by: 1, 4

• Signs of ileus: vomiting, absent passage of stool, decreased bowel sounds
• Signs of toxic megacolon: radiological colonic distension plus severe systemic inflammatory response
• Fever (>38.5°C), abdominal pain, and abdominal distention
• Marked leukocytosis (>15 × 10⁹/L) or marked left shift (>20% bands)
• Colonic wall thickening on CT imaging, pericolonic fat stranding, or ascites
• Microbiological evidence of toxin-producing C. difficile in stool (or rectal swab if no stool available)

Laboratory Testing Strategy

• Send stool (or rectal swab if no stool) for C. difficile testing using a two-step algorithm: initial GDH or PCR for toxin B gene, followed by confirmatory toxin assay if positive. 4
• Do not delay treatment while awaiting confirmatory testing in high-risk patients with clinical signs of severe disease. 1
• Check serum lactate as a marker of severity—elevated lactate indicates need for urgent surgical consultation. 1
• Monitor serum creatinine (>50% rise above baseline indicates severe disease). 1, 4

Imaging Findings

CT abdomen/pelvis will typically show: 1, 4

• Colonic distention (diagnostic of toxic megacolon when >6 cm)
• Colonic wall thickening with low-attenuation mural edema
• Pericolonic fat stranding
• Ascites not explained by other causes

Critical Diagnostic Pitfall

Avoid endoscopy in patients with suspected severe colitis or toxic megacolon, as this significantly increases the risk of perforation or hemorrhage. 1 Endoscopy is only indicated if the diagnosis remains uncertain after non-invasive testing and the patient is stable.

Treatment Approach

Immediate Management

This presentation represents severe CDI that is impossible to treat orally due to ileus, requiring multi-route antibiotic delivery: 1

• IV metronidazole 500 mg every 8 hours (A-III evidence)
• PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours via rectal catheter (C-III evidence)
• AND/OR vancomycin 500 mg four times daily via nasogastric tube (C-III evidence)

The rationale for multi-route therapy is that IV metronidazole alone achieves poor colonic concentrations when ileus is present, necessitating direct colonic delivery of vancomycin. 1

Supportive Care

• Discontinue all inciting antibiotics if clinically feasible and narrow spectrum of any necessary antibiotics. 1
• Absolutely avoid antiperistaltic agents and opiates—these can precipitate or worsen toxic megacolon and mask clinical deterioration. 1, 5
• Provide aggressive IV fluid resuscitation for hemodynamic support. 5
• Correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia.

Surgical Consultation and Timing

Obtain immediate surgical consultation for any patient with: 1

• Toxic megacolon or severe ileus
• Colonic perforation
• Systemic inflammation with deteriorating clinical condition despite antibiotic therapy
• Elevated serum lactate (marker of impending need for surgery)

Colectomy should be performed early, before the patient becomes critically ill, as mortality increases dramatically with delayed surgery. 1 The procedure of choice is subtotal colectomy with end ileostomy.

Monitoring Treatment Response

Assess response after 3 days of therapy by: 4

• Improvement in clinical parameters (decreased fever, abdominal pain, distention)
• Improvement in laboratory markers (decreasing WBC, lactate, creatinine)
• Improvement in radiological findings (decreased colonic distention)
• No new signs of severe disease developing

If no improvement or clinical deterioration occurs within 3-5 days despite maximal medical therapy, proceed urgently to colectomy. 1

Key Clinical Pitfalls

• Never assume absence of diarrhea excludes C. difficile infection in patients with ileus, abdominal distention, fever, and leukocytosis after antibiotic exposure. 2, 3, 6
• Do not treat presumed "constipation" with stool softeners, suppositories, or enemas without first excluding C. difficile—this delays diagnosis and can worsen outcomes. 3
• Avoid relying solely on oral vancomycin when ileus is present, as drug delivery to the colon is severely impaired. 1
• Do not delay surgical consultation until the patient is moribund—early colectomy in deteriorating patients saves lives. 1