What is the likely cause and appropriate management of abdominal pain and diarrhea in a patient who began azithromycin (X‑Pack) and oral prednisone four days ago for a two‑week cough and congestion?

Likely Cause and Management of Abdominal Pain and Diarrhea After Azithromycin and Prednisone

Most Likely Diagnosis

The patient's abdominal pain and diarrhea are most likely caused by azithromycin-induced gastrointestinal side effects, which occur in approximately 33.8% of patients for diarrhea and 17.8% for abdominal pain. 1 These are well-documented adverse effects of azithromycin therapy that typically manifest during or shortly after treatment. 2

Immediate Assessment Required

Rule Out Serious Complications First

• Obtain stool studies immediately to exclude Clostridium difficile infection (CDAI), which can occur with any antibacterial agent including azithromycin and ranges from mild diarrhea to fatal colitis. 2
• Assess for signs of severe colitis: fever ≥38.5°C, bloody stools, severe abdominal pain or distension, or signs of peritoneal irritation. 3
• Check complete blood count, comprehensive metabolic panel, and inflammatory markers (CRP, ESR) to evaluate for anemia from blood loss, electrolyte disturbances, and systemic inflammation. 3

Critical Warning Signs Requiring Immediate Escalation

• Instruct the patient to return immediately if they develop: worsening bloody stools, fever ≥38.5°C, severe abdominal pain or distension, signs of dehydration (decreased urine output, dizziness, tachycardia), or inability to tolerate oral intake. 3
• If C. difficile is confirmed, discontinue azithromycin immediately and initiate appropriate antibiotic treatment directed against C. difficile. 2

Management Algorithm

If Stool Studies Are Negative for Infection

Supportive care is the primary management strategy for azithromycin-induced gastrointestinal symptoms:

• Maintain adequate oral hydration to prevent electrolyte imbalances, as dehydration is a common complication. 1
• Recommend a bland diet during the acute diarrheal period. 1
• Avoid antidiarrheal medications (loperamide) until infectious workup is definitively negative, as these can worsen outcomes if bacterial colitis is present. 1, 3
• Symptoms are typically self-limited and resolve within 1-4 days after completing or discontinuing azithromycin. 1

Prednisone Considerations

• The prednisone prescribed for respiratory symptoms is unlikely to be the primary cause of acute diarrhea after only 4 days of therapy. 1
• However, corticosteroids can alter normal gut flora and may contribute to gastrointestinal symptoms. 2
• Do not discontinue prednisone abruptly if the patient has been on it for several days; taper appropriately if cessation is indicated. 1

Reassessment of Original Antibiotic Indication

Question the Need for Antibiotics

The original prescription of azithromycin for a 2-week cough and congestion was likely inappropriate. 1 Most acute bronchitis cases in otherwise healthy adults are viral and do not benefit from antibiotics. 1

• Acute bronchitis guidelines recommend against routine antibiotic treatment in the absence of pneumonia. 1
• Systematic reviews show limited evidence supporting antibiotics for acute bronchitis, with a trend toward increased adverse events in antibiotic-treated patients. 1
• Patients treated with macrolides (azithromycin) for acute bronchitis had significantly more adverse events than those receiving placebo. 1

Pneumonia Was Likely Not Present

• For healthy immunocompetent adults under 70 years, pneumonia is unlikely in the absence of all of the following: tachycardia (>100 bpm), tachypnea (>24 breaths/min), fever (>38°C), and abnormal chest examination findings (rales, egophony, tactile fremitus). 1
• If these criteria were not met 4 days ago, the azithromycin prescription was unnecessary and has now caused iatrogenic harm. 1

Follow-Up Protocol

Within 24-48 Hours

• Contact the patient by phone or electronic system to assess clinical response and review pending laboratory results. 3
• Verify that symptoms are improving and no warning signs have developed. 3
• Confirm adequate hydration status and ability to maintain oral intake. 1

If Symptoms Persist Beyond 48-72 Hours

• Re-evaluate for alternative diagnoses: inflammatory bowel disease flare, ischemic colitis (especially if older or vascular risk factors), or other infectious etiologies not covered by initial stool studies. 1
• Consider gastroenterology referral if symptoms are severe, persistent, or accompanied by concerning features. 1, 3
• Repeat stool studies including fecal calprotectin if inflammatory bowel disease is suspected. 1

Key Pitfalls to Avoid

• Do not prescribe additional antibiotics empirically without documented bacterial infection, as this increases the risk of C. difficile and antimicrobial resistance. 1, 2
• Do not use antidiarrheal agents until infectious causes are excluded, particularly C. difficile and invasive bacterial pathogens. 1, 3
• Do not dismiss the possibility of C. difficile colitis based on timing alone; CDAD has been reported to occur over 2 months after antibacterial administration. 2
• Recognize that azithromycin's prolonged tissue half-life (up to 5 days) means symptoms may persist or even worsen initially after discontinuation. 2, 4

Documentation and Patient Education

• Document the adverse drug reaction in the patient's medical record and allergy list to prevent future inappropriate prescribing. 2
• Educate the patient that most respiratory infections are viral and self-limited, and that antibiotics are not beneficial and carry risks of adverse effects. 1
• Counsel on appropriate symptomatic management for future respiratory infections: cough suppressants, expectorants, antihistamines, and decongestants as needed. 1