What is the best antibiotic for acute bacterial sinusitis?

Best Antibiotic for Acute Bacterial Sinusitis

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days is the preferred first-line antibiotic for acute bacterial sinusitis in adults, providing superior coverage against β-lactamase-producing organisms and drug-resistant Streptococcus pneumoniae compared to amoxicillin alone. 1, 2

First-Line Treatment Selection

For adults with mild disease and no recent antibiotic use (past 4-6 weeks):

• Amoxicillin-clavulanate 875 mg/125 mg twice daily remains the optimal choice with 90-91% predicted clinical efficacy and 97-99% bacteriologic efficacy 1, 2
• Plain amoxicillin 500 mg twice daily is acceptable only for uncomplicated cases without recent antibiotic exposure, but has lower efficacy (87-88% clinical, 91-92% bacteriologic) 1
• A recent 2021 RCT found no additional benefit from high-dose amoxicillin-clavulanate (1750 mg amoxicillin component) compared to standard dosing, with similar efficacy but increased diarrhea risk 3

For adults with recent antibiotic use (past 4-6 weeks) or moderate-to-severe disease:

• Amoxicillin-clavulanate 875 mg/125 mg twice daily is mandatory as first-line therapy 1, 2
• Respiratory fluoroquinolones (levofloxacin 500-750 mg once daily or moxifloxacin 400 mg once daily) provide 92% clinical efficacy and 100% bacteriologic efficacy, but should be reserved for treatment failures or penicillin allergy 1, 2, 4

Treatment Duration

• Standard duration is 5-10 days, with most guidelines recommending treatment until symptom-free for 7 days (typically 10-14 days total) 2, 5
• Shorter 5-7 day courses have comparable efficacy with fewer side effects 2
• Levofloxacin 750 mg once daily for 5 days is FDA-approved and non-inferior to 10-day regimens 4

Penicillin-Allergic Patients

For non-severe penicillin allergy (e.g., rash):

• Second-generation cephalosporins: cefuroxime axetil 250-500 mg twice daily 1, 2
• Third-generation cephalosporins: cefpodoxime proxetil 200-400 mg twice daily or cefdinir 300 mg twice daily 1, 2
• The risk of cross-reactivity with second- and third-generation cephalosporins in penicillin-allergic patients is negligible 2

For severe Type I hypersensitivity (anaphylaxis):

• Respiratory fluoroquinolones are the only appropriate option: levofloxacin 500 mg once daily for 10 days or moxifloxacin 400 mg once daily for 10 days 1, 2, 5
• Do NOT use azithromycin or other macrolides due to 20-25% resistance rates against S. pneumoniae and H. influenzae 1, 2
• TMP-SMX and doxycycline have limited effectiveness (81-83% clinical efficacy) with 20-25% bacterial failure rates 1

Treatment Failure Protocol

If no improvement after 72 hours (pediatrics) or 3-5 days (adults):

• Switch to respiratory fluoroquinolones (levofloxacin or moxifloxacin) if initially treated with amoxicillin-clavulanate 1, 2
• Consider ceftriaxone 1-2 grams IV once daily if oral therapy fails 1
• Reevaluate the diagnosis—obtain CT scan, fiberoptic endoscopy, or sinus aspiration for culture 1

Pediatric Dosing (Ages 1-18 Years)

Standard therapy (no risk factors):

• Amoxicillin 45 mg/kg/day divided twice daily 1, 5, 6

High-risk patients (age <2 years, daycare attendance, recent antibiotic use within 4 weeks, high local prevalence of resistant S. pneumoniae):

• High-dose amoxicillin-clavulanate 90 mg/kg/day of amoxicillin component with 6.4 mg/kg/day clavulanate in 2 divided doses (maximum 2 g every 12 hours) 1, 5, 6

Penicillin-allergic children:

• Cefpodoxime proxetil 8 mg/kg/day in 2 doses 1, 2
• Cefdinir or cefuroxime axetil are alternatives 1
• Ceftriaxone 50 mg/kg IM/IV once daily for children unable to tolerate oral medication 2

Reassess at 72 hours—if worsening or no improvement, switch to high-dose amoxicillin-clavulanate or ceftriaxone 1, 6

Adjunctive Therapies

• Intranasal corticosteroids reduce mucosal inflammation and may decrease antibiotic use 1, 2, 5
• Short-term oral corticosteroids (e.g., prednisone for 5 days) are reasonable for marked mucosal edema or treatment failure 2
• Saline nasal irrigation improves mucociliary clearance 5
• Analgesics (acetaminophen, NSAIDs) for pain control 2

Critical Pitfalls to Avoid

• Never use azithromycin or clarithromycin as first-line therapy due to high resistance rates (20-25% bacterial failure) 1, 2
• Reserve fluoroquinolones for treatment failures or severe penicillin allergy to prevent resistance development 1, 2
• Do not use doxycycline or TMP-SMX unless absolutely necessary due to limited effectiveness (81-83% clinical efficacy) 1
• Ensure adequate treatment duration (minimum 5 days, typically 7-10 days) to prevent relapse 2, 5
• Reassess at 72 hours (pediatrics) or 3-5 days (adults) if no improvement to avoid treatment failure 1, 6

Special Anatomic Considerations

For frontal, ethmoidal, or sphenoidal sinusitis (not maxillary):

• Respiratory fluoroquinolones (levofloxacin or moxifloxacin) are preferred due to potential for serious complications 1, 2
• These locations require more aggressive initial therapy compared to uncomplicated maxillary sinusitis 1, 2