In a 44-year-old woman with a two-week cough that began after a mild upper respiratory prodrome, now characterized by paroxysmal coughing with post‑tussive vomiting, afebrile, normal respiratory rate and heart rate, clear lungs, and a normal chest radiograph, which empiric therapy is most appropriate: prednisone, antihistamine, inhaled β‑agonist (beta‑agonist), immunoglobulin infusion, or azithromycin (Zithromax)?

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Azithromycin (Zithromax) is the Most Appropriate Empiric Therapy

This clinical presentation is classic for pertussis (whooping cough), and azithromycin should be initiated immediately without waiting for laboratory confirmation. 1, 2, 3

Clinical Diagnosis of Pertussis

The patient's presentation meets the diagnostic criteria for pertussis:

  • Cough lasting >2 weeks with paroxysmal characteristics and post-tussive vomiting are the hallmark features that define pertussis clinically 1, 2, 3
  • The initial mild upper respiratory prodrome (catarrhal phase) lasting approximately 10 days followed by worsening paroxysmal cough is the classic disease progression 2, 3
  • Post-tussive vomiting has high specificity (77.7%) for pertussis—when present, it strongly suggests the diagnosis 3
  • The absence of fever, clear lung examination, and normal chest radiograph are typical findings in pertussis, as the physical examination is often surprisingly unremarkable between coughing episodes 1, 3

Why Azithromycin is the Correct Choice

The American College of Chest Physicians explicitly states: "When the cough is accompanied by paroxysms of coughing, posttussive vomiting, and/or an inspiratory whooping sound, the diagnosis of B. pertussis infection should be made unless another diagnosis is proven." 1

  • Macrolide antibiotics are the drugs of choice for pertussis treatment, with azithromycin preferred as first-line therapy 2, 4
  • Treatment should be initiated immediately upon clinical suspicion without awaiting laboratory confirmation 2, 5
  • Although antibiotics started after the catarrhal phase (which has already passed in this patient) will not significantly alter the clinical course, they are still essential to eradicate B. pertussis from the nasopharynx and prevent transmission to others 1, 2, 6
  • The patient is currently in the most infectious period (first 3 weeks after cough onset), making prompt antibiotic therapy critical for public health 2, 3

Why the Other Options are Incorrect

  • Prednisone (option a): Corticosteroids have no established role in adult pertussis management and are only considered in severe neonatal cases 7
  • Antihistamines (option b): Not indicated for pertussis; the cough is due to airway inflammation and bacterial infection, not histamine-mediated processes 1
  • Inhaled β-agonists (option c): While the ACCP guideline mentions that inhaled ipratropium (an anticholinergic, not a β-agonist) may be helpful for post-infectious cough with airway hyperresponsiveness, this patient's presentation is most consistent with active pertussis infection requiring antimicrobial therapy 1
  • Immunoglobulin infusion (option d): Has no role in pertussis treatment; management relies on antibiotics and supportive care 2, 7

Critical Action Points

  • Isolate the patient for 5 days after starting antibiotic therapy to prevent transmission 2, 3
  • Identify and provide prophylaxis to close contacts, particularly household members and anyone at high risk (infants, pregnant women in third trimester, immunocompromised individuals) 2, 4
  • Azithromycin dosing: Standard adult regimen is 500 mg on day 1, then 250 mg daily for days 2-5 4

Common Pitfall to Avoid

Do not dismiss pertussis in vaccinated adults. Neither vaccination nor natural infection confers lifelong immunity, with protective immunity waning 5-10 years after the last pertussis-containing vaccine dose. 2 The illness can present with milder symptoms and absent whoop in previously vaccinated individuals. 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Pertussis (Whooping Cough): Clinical Features, Epidemiology, and Preventive Strategies

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Pertussis Clinical Presentation and Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Pertussis: Common Questions and Answers.

American family physician, 2021

Guideline

Supportive Care for Infants with Pertussis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Antibiotics for whooping cough (pertussis).

The Cochrane database of systematic reviews, 2007

Research

Current pharmacotherapy of pertussis.

Expert opinion on pharmacotherapy, 2001

Professional Medical Disclaimer

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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