What are the next steps for a patient with a 2-week history of nausea, vomiting, and diarrhea with fever, who experiences a pattern of improvement followed by recurrence?

Immediate Diagnostic Workup and Management

This patient requires urgent evaluation for Clostridioides difficile infection (CDI) and other breakthrough infections, with immediate stool testing, blood cultures, and consideration of abdominal imaging given the recurrent fever pattern. 1

Initial Assessment and Testing

The pattern of improvement followed by recurrence over 2 weeks with fever is highly concerning for:

• Test stool immediately for C. difficile toxin using enzyme immunoassay or 2-step antigen/toxin assay, as breakthrough CDI is common in patients with persistent symptoms 1
• Obtain new blood cultures to evaluate for bacteremia or catheter-related bloodstream infection if any vascular access is present 1
• Check fecal lactoferrin to assess for inflammatory diarrhea, as positive results warrant more aggressive evaluation even with mild symptoms 1
• Consider abdominal CT imaging if patient has abdominal pain, as this evaluates for neutropenic enterocolitis or other intra-abdominal pathology 1

The recurrent fever pattern specifically suggests that this is not simple viral gastroenteritis and requires investigation for bacterial or parasitic causes 2.

Rehydration as Priority

While diagnostic workup proceeds:

• Administer reduced osmolarity oral rehydration solution (ORS) at 50-100 mL/kg over 2-4 hours for mild-moderate dehydration 2, 3
• Use isotonic IV fluids (normal saline or lactated Ringer's) in 20 mL/kg boluses if severe dehydration, shock, or inability to tolerate oral intake 2, 3
• Replace ongoing losses with 10 mL/kg for each watery stool and 2 mL/kg per vomiting episode 3

Empiric Antimicrobial Therapy Considerations

Start empiric antimicrobial therapy immediately if:

• Fever ≥38.5°C with signs of sepsis 2
• Bloody diarrhea is present 2
• Patient is immunocompromised 2
• Severe illness with hemodynamic instability 1

If C. difficile is strongly suspected clinically (recurrent symptoms, recent antibiotic exposure, abdominal cramping):

• Begin empiric treatment with oral vancomycin 125 mg four times daily OR metronidazole 500 mg three times daily while awaiting test results 1
• Do not delay treatment in high-risk patients, as early intervention improves outcomes 1

Endoscopy Timing

Perform endoscopy within 7-14 days of symptom onset if:

• Fecal lactoferrin is positive 1
• Symptoms persist despite initial management 1
• Bloody diarrhea or severe abdominal pain develops 1

Early endoscopy (≤7 days) is associated with significantly shorter symptom duration (19 vs 47 days) and reduced steroid treatment duration compared to delayed endoscopy 1.

Adjunctive Management

• Avoid antimotility agents (loperamide, diphenoxylate/atropine) given the presence of fever, as these increase risk of toxic megacolon in inflammatory diarrhea 1, 2
• Consider ondansetron 4-8 mg for persistent vomiting to facilitate oral rehydration 2, 4
• Resume age-appropriate diet immediately once rehydrated; do not withhold food 2, 5

Red Flags Requiring Hospitalization

Admit to hospital if:

• Severe dehydration not responding to oral rehydration 3
• Persistent vomiting preventing oral intake 3
• Altered mental status or signs of shock 3
• Fever with abdominal distention or severe tenderness (concern for perforation) 1

Common Pitfalls to Avoid

• Do not dismiss recurrent fever as "just viral" – this pattern demands investigation for bacterial superinfection or CDI 1
• Do not use antibiotics empirically for simple watery diarrhea without fever or high-risk features, but this patient's recurrent fever pattern warrants consideration 2
• Do not delay C. difficile testing in patients with persistent or recurrent symptoms, as breakthrough CDI occurs frequently 1
• Do not use antimotility agents when fever is present, as this can precipitate toxic megacolon 1, 2

Follow-up Strategy

• Recheck hydration status after 2-4 hours of rehydration therapy 3
• Modify or discontinue antimicrobials once specific pathogen identified or ruled out 2
• If symptoms persist beyond 5-7 days despite negative workup, consider non-infectious causes including inflammatory bowel disease, medication effects, or functional disorders 2, 6