A 53-year-old man diagnosed with pneumonia ten days ago and now improving respiratory-wise presents with two days of watery, non‑bloody diarrhea (~10 stools per day), fever, and abdominal pain after receiving broad‑spectrum antibiotics; what is the most likely diagnosis and recommended management?

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Antibiotic-Associated Diarrhea with Suspected Clostridioides difficile Infection

This patient's presentation—watery diarrhea (~10 episodes/day), fever, and abdominal pain developing 2 days after broad-spectrum antibiotic therapy for pneumonia—is highly suspicious for Clostridioides difficile infection (CDI), which should be tested immediately and treated empirically while awaiting results. 1


Immediate Diagnostic Approach

  • Send stool for C. difficile testing using enzyme immunoassay or the 2-step antigen/toxin assay—this is the single most important test given recent antibiotic exposure, fever, abdominal pain, and high-frequency watery diarrhea. 1
  • Do NOT routinely order stool bacterial cultures, ova/parasites, or fecal white blood cell counts in hospitalized patients with antibiotic-associated diarrhea, as CDI is the overwhelming concern in this setting. 1
  • The combination of recent antibiotics + fever + abdominal pain + watery diarrhea (≥3 unformed stools/24 hours) meets clinical criteria for empirical CDI treatment even before test results return. 1

Empirical Treatment While Awaiting Test Results

  • Start oral vancomycin 125 mg four times daily OR oral fidaxomicin 200 mg twice daily immediately without waiting for test confirmation, given the high pretest probability and potential for rapid deterioration. 1, 2
  • Oral metronidazole 500 mg three times daily is an alternative if vancomycin/fidaxomicin are unavailable, though it is no longer first-line due to lower cure rates and higher recurrence. 1
  • Continue the pneumonia antibiotics (ceftriaxone + azithromycin or equivalent) to completion, as stopping them prematurely risks pneumonia treatment failure—CDI treatment addresses the superinfection. 1, 3

Clinical Severity Assessment

  • This patient has "complicated" CDI based on the presence of fever and abdominal pain alongside diarrhea, which mandates closer monitoring and potentially more aggressive management. 1
  • Monitor for signs of severe/fulminant CDI: white blood cell count >15,000/μL, serum creatinine >1.5× baseline, hypotension, ileus, or toxic megacolon—any of these would require escalation to vancomycin 500 mg PO/NG four times daily ± IV metronidazole 500 mg every 8 hours. 1
  • Consider abdominal CT if the patient develops worsening abdominal pain, distension, or signs of peritonitis to evaluate for toxic megacolon, perforation, or neutropenic enterocolitis (though the latter is less likely without neutropenia). 1

Duration and Follow-Up

  • Treat CDI for 10 days with oral vancomycin or fidaxomicin once the diagnosis is confirmed. 2
  • Reassess at 48–72 hours: if diarrhea persists or worsens despite therapy, repeat stool testing and consider alternative diagnoses (viral gastroenteritis, other bacterial pathogens, inflammatory bowel disease). 1
  • Do NOT use antidiarrheal agents (loperamide, diphenoxylate) in suspected CDI, as they may precipitate toxic megacolon by impairing toxin clearance. 1, 4

Alternative or Concurrent Diagnoses to Consider

  • Antibiotic-associated diarrhea without CDI (osmotic/secretory diarrhea from altered gut flora) is possible but less likely given fever and abdominal pain—this typically resolves with supportive care alone. 1
  • Viral gastroenteritis (norovirus, rotavirus) can mimic CDI but usually lacks the severe abdominal pain and is less common in adults without epidemic exposure. 1
  • Bacterial enteritis (Salmonella, Campylobacter, Shigella) is unlikely given the absence of bloody stools and the temporal relationship to antibiotics rather than food/water exposure. 1
  • Pneumococcal enteritis with bacteremia is an exceedingly rare cause of acute diarrhea and fever but has been reported in elderly patients with pneumococcal pneumonia—blood cultures (if drawn) may clarify this. 5

Critical Pitfalls to Avoid

  • Never delay empirical CDI treatment in a patient with recent antibiotics, fever, abdominal pain, and high-frequency diarrhea—waiting for test results risks progression to severe/fulminant disease. 1
  • Do not stop the pneumonia antibiotics prematurely to "treat" the diarrhea—this risks pneumonia relapse and does not address established CDI, which requires specific anti-CDI therapy. 1, 3
  • Avoid indiscriminate stool testing (bacterial cultures, O&P) in hospitalized patients with antibiotic-associated diarrhea, as these rarely change management and CDI testing is the priority. 1
  • Do not use metronidazole as first-line therapy if vancomycin or fidaxomicin are available, as it has inferior sustained response rates (57% vs. 70% for vancomycin). 2

Supportive Care

  • Aggressive IV fluid resuscitation with isotonic crystalloid to correct dehydration (dry mucous membranes, tachycardia, decreased urination). 1
  • Monitor electrolytes (potassium, magnesium) and replace as needed, as secretory diarrhea causes significant losses. 1
  • Discontinue proton pump inhibitors if the patient is on them, as they increase CDI risk and recurrence. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Antibiotic Regimen Recommendations for Community-Acquired Pneumonia in Adults

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Severe acute diarrhea.

Gastroenterology clinics of North America, 2003

Research

Acute enteritis associated with pneumococcal bacteremia.

The Journal of the Association of Physicians of India, 2009

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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