What is the next step in managing a 44-year-old female with persistent fatigue and dry cough despite completing a 2-week course of azithromycin (Zithromax) and other medications?

Management of Persistent Dry Cough After Failed Antibiotic Therapy

Order a chest X-ray immediately to exclude pneumonia, structural abnormalities, or other serious pathology, then initiate empiric treatment with a first-generation antihistamine-decongestant combination for upper airway cough syndrome (UACS). 1, 2

Immediate Diagnostic Step

• Obtain a chest radiograph now to rule out persistent pneumonia, masses, interstitial disease, or congestive heart failure in this patient with chronic cough (>3 weeks duration). 2
• This patient's cough has persisted for at least 5 weeks total (2 weeks of treatment plus 2+ weeks post-treatment), qualifying as subacute cough (3-8 weeks). 1

Most Likely Diagnosis: Post-Infectious Cough with UACS

• The clinical presentation—dry persistent cough following respiratory infection that failed to resolve with antibiotics—strongly suggests post-infectious cough and/or upper airway cough syndrome. 1
• Multiple pathogenetic factors contribute: postviral airway inflammation, bronchial hyperresponsiveness, mucus hypersecretion, and impaired mucociliary clearance. 3, 1
• The fatigue and "worn down" feeling are consistent with post-viral syndrome. 1

First-Line Treatment Protocol

Start with antihistamine-decongestant therapy:

• Prescribe a first-generation antihistamine/decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine). 1, 2
• Begin with once-daily bedtime dosing for 2-3 days, then advance to twice-daily to minimize sedation. 1
• Add intranasal corticosteroid spray (e.g., fluticasone, mometasone) to decrease airway inflammation. 1
• Monitor for side effects: urinary retention, increased intraocular pressure, sedation, insomnia, jitteriness, tachycardia, and worsening hypertension. 1

Second-Line Options if No Improvement in 1-2 Weeks

If UACS treatment fails:

• Trial inhaled ipratropium bromide 2-3 puffs four times daily, which has been shown to attenuate post-infectious cough with fewer systemic side effects. 3, 1
• Consider inhaled corticosteroids (e.g., budesonide, fluticasone) if cough persists and adversely affects quality of life. 3, 1

For severe paroxysmal cough:

• Prescribe prednisone 30-40 mg daily for 5-7 days only after ruling out other causes (asthma, GERD). 3, 2
• Add central-acting antitussives (codeine 15-30 mg or dextromethorphan 30 mg every 6 hours) when other measures fail. 3, 1

Systematic Evaluation if Treatment Fails

After 2 weeks of adequate UACS therapy without improvement, evaluate sequentially for:

1. Asthma/Non-Asthmatic Eosinophilic Bronchitis:

   • The prior prednisone taper and albuterol suggest asthma was already considered, but reassess with spirometry and bronchoprovocation if not previously done. 2
   • Response to bronchodilators occurs within 1 week, with complete resolution taking up to 8 weeks. 2

2. Gastroesophageal Reflux Disease (GERD):

   • If both UACS and asthma treatments fail, initiate high-dose PPI therapy (e.g., omeprazole 40 mg twice daily), dietary modifications, and lifestyle changes. 3, 2
   • GERD-related cough may require 2 weeks to several months for response, with some patients needing 8-12 weeks. 3, 2
   • Consider adding prokinetic therapy (metoclopramide) if no response to PPI alone. 3

Advanced Testing if All Empiric Therapy Fails

Only after adequate therapeutic trials (minimum 2 weeks each) of UACS, asthma, and GERD:

• Order high-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses. 3, 2
• Consider bronchoscopy to evaluate for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection. 3, 2
• Order 24-hour esophageal pH monitoring if GERD remains suspected despite failed empiric therapy. 3, 2

Critical Pitfalls to Avoid

• Do not repeat antibiotics—this patient already failed azithromycin, and post-infectious cough is not bacterial. 3
• Do not use nasal decongestant sprays >3-5 days due to rebound congestion risk. 1
• Do not diagnose "unexplained cough" until completing systematic evaluation of UACS, asthma, and GERD with adequate treatment trials. 2
• Pertussis should be considered if paroxysmal cough with post-tussive vomiting or inspiratory whoop develops, though this is less likely given the clinical picture. 3