What is the most likely diagnosis in a 22‑year‑old patient presenting with leukocytosis, lactic acidosis, fever, lower abdominal pain, proctitis extending to the cecum, and negative blood, urine, and stool cultures?

Diagnosis: Clostridioides difficile Infection (CDI)

The most likely diagnosis in this 22-year-old patient with leukocytosis, lactic acidosis, fever, lower abdominal pain, and inflammation extending from the rectum to the cecum with negative cultures is severe Clostridioides difficile infection (CDI), which can present with negative initial stool cultures and requires specific C. difficile toxin testing for diagnosis. 1

Clinical Presentation Matches Severe CDI

This patient's constellation of findings is highly characteristic of severe CDI:

• Marked leukocytosis is a hallmark of severe colitis and specifically listed as a criterion for severe CDI (leukocyte count >15 × 10⁹/L) 1
• Elevated serum lactate is an established marker of severe colitis and correlates with disease severity 1
• Fever (core body temperature >38.5°C) is a defining sign of severe colitis 1
• Lower abdominal pain with colonic inflammation (proctitis extending to cecum) represents the typical distribution of CDI, which can involve any portion of the colon 1

Critical Diagnostic Pitfall: Negative Cultures Do Not Exclude CDI

The negative blood, urine, and stool cultures mentioned do NOT rule out CDI because standard bacterial cultures do not detect C. difficile toxins. 1 This is a common diagnostic error that can delay life-saving treatment.

• Standard stool cultures do not identify toxin-producing C. difficile 1
• Specific testing is required: C. difficile toxin assay (enzyme immunoassay for toxins A/B) or nucleic acid amplification test (NAAT) for toxigenic strains 1
• The diagnosis requires "microbiological evidence of toxin-producing C. difficile in stools" 1

Severe Disease Classification

This patient meets multiple criteria for severe CDI based on ESCMID guidelines 1:

• Marked leukocytosis (>15 × 10⁹/L)
• Elevated serum lactate
• Fever
• Abdominal pain with extensive colonic involvement
• Lower abdominal pain suggesting possible peritoneal signs

The 2019 WSES guidelines emphasize that patients with profound leukocytosis (>18,000/mm³), hemodynamic instability, and elevated lactate are at risk for fulminant colitis 1

Differential Considerations

While the presentation could theoretically suggest other conditions, several factors make CDI most likely:

• Inflammatory bowel disease (IBD) typically has a more chronic presentation in a 22-year-old, though acute severe colitis can occur. However, the combination of lactic acidosis and marked leukocytosis is more characteristic of infectious/toxin-mediated colitis 1
• Ischemic colitis would be unusual in a 22-year-old without risk factors (cardiac failure, low flow states, vasopressor use) 1
• Other infectious colitis would typically show positive stool cultures for common pathogens 1

The fact that inflammation extends from rectum (proctitis) to cecum suggests pancolitis, which can occur with severe CDI and carries worse prognosis 1

Immediate Management Algorithm

For severe CDI (which this patient has), treatment should be initiated immediately without waiting for confirmatory testing: 1

1. If oral therapy is possible:

   • Vancomycin 125 mg four times daily orally for 10 days (A-I recommendation) 1
   • Avoid metronidazole monotherapy in severe disease 1

2. If oral therapy is impossible or patient has ileus:

   • Metronidazole 500 mg three times daily intravenously PLUS
   • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 1

3. Critical management principles:

   • Avoid antiperistaltic agents and opiates (B-II recommendation) 1
   • Stop any inciting antibiotics if possible 1
   • Monitor closely for signs of fulminant colitis or toxic megacolon 1

When to Consider Surgery

Early surgical consultation is mandatory given the severity of presentation 1:

• Patients with lactate ≥5 mmol/L, leukocytosis ≥50 × 10⁹/L, age ≥75 years, or shock requiring vasopressors have high mortality risk 1
• Emergency colectomy should be performed for: perforation, toxic megacolon with systemic toxicity, or failure to respond to medical therapy within 3-5 days 1
• Total colectomy with end ileostomy is the standard surgical approach, though diverting loop ileostomy with colonic lavage is an alternative 1

Essential Next Steps

1. Order C. difficile-specific testing immediately (toxin EIA or NAAT) 1
2. Initiate empiric treatment with oral vancomycin without waiting for test results given severe presentation 1
3. Obtain CT imaging if not already done to assess for complications (colonic wall thickening, pericolonic fat stranding, ascites, megacolon) 1
4. Request urgent surgical consultation given severity markers 1
5. Monitor treatment response at 3 days (decreased stool frequency, improved consistency, no new signs of severe colitis) 1