What's the next step for an adult patient with no significant past medical history and sinusitis not relieved by azithromycin (Zithromax) for three days?

Switch to Amoxicillin-Clavulanate Immediately

For an adult with sinusitis not responding to azithromycin after three days, switch to high-dose amoxicillin-clavulanate (875 mg/125 mg twice daily) for 10-14 days. 1

Why Azithromycin Failed

Azithromycin should never have been prescribed as first-line therapy for acute bacterial sinusitis due to significant resistance patterns:

• Resistance rates exceed 20-25% for both Streptococcus pneumoniae and Haemophilus influenzae, the two most common bacterial pathogens in sinusitis 1
• The American Academy of Pediatrics explicitly states that azithromycin should not be used to treat acute bacterial sinusitis due to these resistance patterns 1
• French guidelines exclude macrolides, including azithromycin, from recommended therapy due to resistance prevalence 1

Correct Second-Line Treatment

Switch to amoxicillin-clavulanate 875 mg/125 mg twice daily for 10-14 days (or until symptom-free for 7 days): 1, 2

• This provides coverage against β-lactamase-producing H. influenzae and M. catarrhalis, which azithromycin likely failed to eradicate 1
• Amoxicillin-clavulanate achieves 90-92% predicted clinical efficacy for acute bacterial sinusitis 1
• The clavulanate component specifically targets β-lactamase-producing organisms that render azithromycin ineffective 1

Alternative Options If Penicillin Allergy Exists

For non-severe penicillin allergy (rash, mild reactions):

• Second-generation cephalosporins: cefuroxime-axetil 1, 3
• Third-generation cephalosporins: cefpodoxime-proxetil or cefdinir 1, 3
• These have negligible cross-reactivity risk with penicillin allergy 1

For severe penicillin allergy (anaphylaxis):

• Respiratory fluoroquinolones: levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10 days 1, 3
• These provide 90-92% predicted clinical efficacy against drug-resistant S. pneumoniae and β-lactamase-producing H. influenzae 1

Critical Reassessment Timeline

• Reassess at 3-5 days after starting the new antibiotic 1
• If no improvement occurs, consider:
  • Switching to a respiratory fluoroquinolone 1
  • Re-evaluating the diagnosis (may not be bacterial sinusitis) 1
  • Checking for complications (orbital cellulitis, meningitis) 1
  • Referring to otolaryngology if symptoms are refractory to two courses of appropriate antibiotics 1

Add Adjunctive Therapies

Intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily):

• Strongly recommended to reduce mucosal inflammation and improve symptom resolution 1, 2
• Can be continued throughout antibiotic therapy 1

Symptomatic relief measures:

• Analgesics (acetaminophen or NSAIDs) for pain 1
• Saline nasal irrigation for symptomatic relief 1
• Adequate hydration, warm facial packs, sleeping with head elevated 1

Common Pitfall to Avoid

Never continue azithromycin or switch to another macrolide (clarithromycin, erythromycin), as resistance rates exceed 40% for S. pneumoniae in the United States, making treatment failure highly likely. 1, 3