What is the best course of treatment for a patient with a history of a 3-week productive cough last month, which resolved with empiric antibiotics (e.g. azithromycin or amoxicillin-clavulanate) and supportive treatment, and a negative Tuberculosis (TB) workup, who now presents with a relapse of cough symptoms for 1 week?

Management of Relapsed Productive Cough After Recent Resolution

This patient has postinfectious cough, and antibiotics are explicitly contraindicated—they provide no benefit and contribute to antimicrobial resistance. 1

Clinical Context and Diagnosis

This presentation fits the classic pattern of postinfectious cough, defined as cough persisting 3-8 weeks following an acute respiratory infection. 2 The patient's timeline—initial 3-week productive cough that resolved, now relapsing at 1 week—places them in the acute-to-subacute window where viral inflammation and bronchial hyperresponsiveness are the primary drivers. 1

Key diagnostic features that exclude bacterial infection include: 1

• Non-purulent sputum
• No fever
• Clear lungs (except transient wheezes that clear with coughing)
• No crackles suggesting pneumonia
• Otherwise healthy nonsmoker

The fact that colored or green sputum may be present does not indicate bacterial infection—this simply reflects inflammatory cells and debris from viral infection. 3 The previous negative TB workup and symptom resolution with supportive care further support a non-bacterial etiology.

Treatment Algorithm

First-Line: Supportive Care (Current Phase - Week 1)

Start with over-the-counter supportive measures: 1

• Guaifenesin 200-400 mg every 4 hours (up to 6 times daily) to help loosen phlegm and thin bronchial secretions 1
• Honey for cough suppression 4
• Warm fluids 3
• Adequate hydration 4
• Acetaminophen for associated discomfort 4

Consider adding symptomatic relief: 2, 3

• First-generation antihistamine/decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) if postnasal drip is suspected 1, 4
• Naproxen may favorably affect cough 2, 4
• Dextromethorphan 60 mg for maximum cough suppression effect 3

Second-Line: Inhaled Ipratropium (If Symptoms Persist 1-2 Weeks)

If quality of life becomes significantly affected after 1-2 weeks of supportive care, escalate to inhaled ipratropium bromide 2-3 puffs (17-34 mcg per puff) four times daily. 1 This has the strongest evidence for attenuating postinfectious cough, with expected response within 1-2 weeks. 1

Third-Line: Inhaled Corticosteroids (If Cough Persists Beyond 3-4 Weeks)

If quality of life remains significantly affected despite ipratropium treatment, consider inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily), with response time up to 8 weeks. 2, 1

Reserve Oral Corticosteroids for Severe Cases Only

Prednisone 30-40 mg daily for 5-10 days should only be prescribed if severe paroxysms significantly impair quality of life and other common causes (upper airway cough syndrome, asthma, GERD) have been ruled out. 2, 1 This is not appropriate for mild relapsed cough at 1 week.

Critical Pitfall to Avoid

Do not prescribe antibiotics (amoxicillin, azithromycin, or others) for this relapsed cough. 1 The American College of Chest Physicians explicitly states that antibiotics have no role in postinfectious cough because the cause is not bacterial infection. 2, 1 Inappropriate antibiotic use contributes to resistance and provides no clinical benefit. 3

The only exceptions where antibiotics would be appropriate are: 2, 1

• Clear evidence of bacterial sinusitis
• Early Bordetella pertussis infection (which would present differently with characteristic paroxysms and inspiratory whoop)

When to Reassess

Red flags requiring immediate re-evaluation: 1, 3

• Development of fever
• Hemoptysis
• Dyspnea or respiratory distress
• Weight loss or night sweats
• Abnormal lung examination findings (persistent crackles, clubbing)

If cough persists beyond 8 weeks, this transitions to chronic cough requiring systematic evaluation for: 2, 1

• Upper airway cough syndrome (UACS)
• Asthma (consider bronchoprovocation challenge or empiric inhaled corticosteroids/beta-agonists)
• Gastroesophageal reflux disease (GERD—consider high-dose PPI therapy)

Chronic cough is frequently multifactorial, and all contributing causes must be treated for resolution. 1 Chest X-ray should be obtained if cough persists beyond 8 weeks or if any red flags develop. 1