A patient treated two weeks ago with amoxicillin‑clavulanate (Augmentin) for ten days and a prednisone (Medrol) dose pack now has persistent cough and systemic symptoms; what further management or medication should be given?

Persistent Cough After Augmentin and Prednisone: Next Steps

Add a macrolide antibiotic (azithromycin 500 mg daily for 5 days or clarithromycin 500 mg twice daily for 10–14 days) to cover atypical bacterial pathogens that are not susceptible to amoxicillin-clavulanate. 1

Clinical Reassessment Required

Before prescribing additional medication, determine whether this represents treatment failure requiring antibiotic change versus expected post-infectious cough:

• Persistent fever (≥38.5°C) beyond 3 days of completing antibiotics strongly suggests bacterial infection that was inadequately treated and warrants immediate antibiotic change 1
• Systemic symptoms (malaise, worsening dyspnea, increased sputum production or purulence) indicate ongoing active infection requiring different antimicrobial coverage 1
• Isolated cough without fever or systemic symptoms may represent post-infectious airway hyperreactivity rather than treatment failure, as cough can persist for weeks after successful bacterial eradication 1

Antibiotic Switch Strategy

When to Add or Switch Antibiotics

Failure of amoxicillin-clavulanate after 48–72 hours suggests atypical bacterial pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae) that require macrolide monotherapy 1

• First-line macrolide options:

  • Azithromycin 500 mg orally once daily for 5 days 2
  • Clarithromycin 500 mg orally twice daily for 10–14 days 2
  • These agents provide coverage against atypical pathogens and alternative coverage for Streptococcus pneumoniae 2

• For nonspecific clinical symptoms or lack of improvement with monotherapy, combined treatment with amoxicillin plus a macrolide may be used 1

• Atypical pneumonia requires at least 14 days of macrolide therapy for adequate treatment 1

Alternative Second-Line Options

If macrolides are contraindicated or ineffective after 48 hours:

• Respiratory fluoroquinolones (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) for 5–7 days provide broad coverage including resistant S. pneumoniae and atypical pathogens 1, 3
• Second-generation cephalosporins (cefuroxime-axetil) or third-generation cephalosporins (cefpodoxime-proxetil) can be considered, though they lack atypical pathogen coverage 1, 3

Reassessment Timeline

• Evaluate clinical response 48–72 hours after initiating new antibiotic therapy; fever should resolve within this window if bacterial infection is responding 1, 3
• If no improvement after 5 days of appropriate therapy, consider alternative diagnoses (viral infection, post-viral cough, bronchiectasis, tuberculosis, malignancy) and obtain chest imaging if not already performed 1
• Hospitalization is warranted if no improvement or worsening condition occurs after 5 days of combined therapy 1

Management of Isolated Post-Infectious Cough

If the patient is afebrile without systemic symptoms, the persistent cough likely represents post-infectious airway hyperreactivity rather than ongoing infection:

• Do not prescribe additional antibiotics for isolated cough without fever or systemic symptoms, as this increases antimicrobial resistance without benefit 3
• Consider bronchodilator therapy or inhaled corticosteroids for symptomatic relief of post-infectious cough 1
• Evaluate for upper airway cough syndrome (UACS) with first-generation antihistamine-decongestant therapy if nasal symptoms are present 1
• Consider bronchoprovocation challenge testing to evaluate for asthma as a contributing factor 1

Critical Pitfalls to Avoid

• Do not continue ineffective amoxicillin-clavulanate beyond 5–7 days without clinical improvement, as this represents treatment failure requiring antibiotic change 2, 3
• Do not overlook atypical pathogens (Mycoplasma, Chlamydophila), which require macrolide coverage and are a common cause of amoxicillin failure 1, 2
• Do not prescribe additional corticosteroids (another Medrol dose pack) without clear indication, as the patient already received a steroid course and prolonged corticosteroid use increases infection risk and immunosuppression 4
• Persistent cough alone does not constitute treatment failure if the patient is otherwise improving; cough may linger for weeks after successful infection resolution 1, 3

When to Consider Imaging or Specialist Referral

• Obtain chest X-ray if not already performed to rule out pneumonia, atelectasis, or other radiological abnormalities 1
• Consider hospitalization or pulmonology referral for worsening symptoms despite appropriate antibiotic changes, development of complications (pleural effusion, abscess), or inability to maintain oral intake 1, 2
• Rule out tuberculosis, inhaled foreign body, or malignancy in patients with persistent symptoms unresponsive to multiple antibiotic courses 1