In a 58‑year‑old man with metastatic colon cancer post‑rectosigmoid resection on chemotherapy, now neutropenic with fever, colicky abdominal pain and persistent watery diarrhea while receiving ceftriaxone and metronidazole, what is the most likely diagnosis and recommended management?

Diagnosis: Neutropenic Enterocolitis (Typhlitis) with Possible Clostridium difficile Superinfection

This patient has neutropenic enterocolitis until proven otherwise, and the current antibiotic regimen is inadequate—immediate escalation to anti-pseudomonal coverage with vancomycin for C. difficile is mandatory. 1

Critical Diagnostic Considerations

The combination of profound neutropenia (ANC 112), persistent diarrhea, colicky abdominal pain, and recent chemotherapy in a colon cancer patient creates a life-threatening scenario with mortality rates approaching 29.5% to 81% depending on severity. 1

Primary Diagnosis: Neutropenic Enterocolitis (Typhlitis)

• Neutropenic enterocolitis develops during the second-third week after chemotherapy when mucosal damage from cytotoxic drugs allows bacterial invasion of the bowel wall 1
• The colicky abdominal pain pattern is characteristic of bowel wall inflammation and potential ischemia 1
• Mortality reaches 60% when bowel wall thickening exceeds 10mm on imaging 1
• The declining ANC despite filgrastim (237→112) indicates severe bone marrow suppression and poor prognosis 1

High-Risk Concurrent Diagnosis: C. difficile Infection

• C. difficile accounts for up to 50% of antibiotic-associated diarrhea and occurs in 5-20% of cancer patients on chemotherapy 1
• The current ceftriaxone and metronidazole regimen itself increases C. difficile risk 1
• In neutropenic patients, pseudomembrane formation may be absent or altered because neutrophils are required for typical appearance 1
• Leukocytosis cannot be used as a severity criterion in neutropenic patients, making clinical assessment more challenging 1

Immediate Management Algorithm

Step 1: Urgent Imaging (Within 2-4 Hours)

Order abdominal CT scan with IV contrast immediately to assess:

• Bowel wall thickening (particularly right colon/cecum) >10mm indicates high mortality risk 1
• Signs of perforation, pneumatosis intestinalis, or portal venous gas 1
• Presence of abscess formation or free fluid 1
• Toxic megacolon or bowel ischemia 1

Step 2: Escalate Antibiotic Coverage Immediately (Do Not Wait for Imaging)

The current regimen of ceftriaxone plus metronidazole is inadequate for neutropenic enterocolitis. 1

Switch to:

• Anti-pseudomonal beta-lactam: Piperacillin-tazobactam 4.5g IV q6h OR meropenem 1g IV q8h OR cefepime 2g IV q8h 1
• ADD vancomycin 125mg PO q6h for empiric C. difficile coverage (do not wait for stool toxin results, as testing sensitivity is only 50-80% and neutropenic patients may lack typical findings) 1
• Consider adding metronidazole 500mg IV q8h if oral vancomycin absorption is questionable due to ileus 1

Step 3: Obtain Diagnostic Studies

• Stool testing: C. difficile toxin A/B by EIA AND PCR for toxin B gene (dual testing increases sensitivity) 1
• Blood cultures × 2 sets before antibiotic escalation 1
• Complete metabolic panel to assess for organ dysfunction (creatinine, bilirubin, lactate) 1
• Do NOT perform colonoscopy—carries very high perforation risk in neutropenic enterocolitis 1

Step 4: Supportive Care

• Bowel rest: NPO status with IV hydration 1
• Parenteral nutrition if prolonged course anticipated 1
• Continue filgrastim 5 mcg/kg/day subcutaneously until ANC >1000 for two consecutive days 2
• Aggressive fluid resuscitation targeting urine output >0.5 mL/kg/h 1

Step 5: Surgical Consultation

Obtain immediate surgical consultation for potential emergency intervention if: 1

• CT shows perforation, pneumoperitoneum, or portal venous gas
• Clinical deterioration despite 24-48 hours of appropriate antibiotics
• Persistent GI bleeding
• Development of toxic megacolon (colon diameter >6cm)
• Signs of bowel ischemia or necrosis

Mortality for emergency surgery during chemotherapy-induced neutropenia reaches 57-81%, but surgery is life-saving when perforation or ischemia occurs. 1

Critical Pitfalls to Avoid

Do not continue current inadequate antibiotic regimen: Ceftriaxone lacks adequate anti-pseudomonal coverage required for neutropenic enterocolitis, and metronidazole alone is insufficient for C. difficile in severe cases 1

Do not delay imaging: Bowel wall thickness >10mm predicts 60% mortality versus 4.2% if <10mm—early identification allows risk stratification 1

Do not perform endoscopy: Colonoscopy carries extremely high perforation risk in inflamed, neutropenic bowel 1

Do not withhold vancomycin pending stool results: Neutropenic patients may have atypical C. difficile presentations without pseudomembranes, and toxin assay sensitivity is only 50-80% 1

Do not assume filgrastim failure means futility: Resolution of neutropenic enterocolitis directly correlates with neutrophil recovery—continue G-CSF support 1

Prognosis and Monitoring

• Resolution occurs in 86% of patients with conservative management when treated appropriately, typically within 6-8 days 1
• Daily monitoring required: Stool frequency, abdominal exam, vital signs, renal function, and repeat ANC 3
• Rising neutrophil count after nadir directly correlates with symptom resolution 1
• If no improvement within 48-72 hours despite appropriate antibiotics, consider adding empiric antifungal coverage (micafungin 100mg IV daily or caspofungin) 1