Which oral antibiotic is first‑line for an adult with acute bacterial sinusitis presenting with symptoms ≥10 days or worsening after initial improvement, fever ≥39 °C, purulent nasal discharge, and facial pain/pressure, and what are the alternatives for penicillin allergy or resistant Streptococcus pneumoniae?

First-Line Antibiotic for Acute Bacterial Sinusitis

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days is the preferred first-line antibiotic for adults with acute bacterial sinusitis. 1, 2, 3

Confirming the Diagnosis Before Prescribing

Before prescribing any antibiotic, verify the patient meets criteria for acute bacterial rhinosinusitis (ABRS) rather than viral rhinosinusitis, as 98-99.5% of acute rhinosinusitis is viral and resolves spontaneously within 7-10 days. 1, 3

Diagnose ABRS when one of three patterns is present: 1, 3

• Persistent symptoms ≥10 days without improvement (purulent nasal discharge with nasal obstruction, facial pain/pressure, or both)
• Severe symptoms ≥3-4 consecutive days (fever ≥39°C with purulent nasal discharge and facial pain)
• "Double sickening" – worsening after initial improvement within 10 days

First-Line Treatment: Amoxicillin-Clavulanate

Standard dosing: 875 mg/125 mg twice daily for 5-10 days 1, 2, 3

High-dose regimen (2 g/125 mg twice daily) when: 2, 3

• Recent antibiotic use within past 4-6 weeks
• Age >65 years
• Moderate-to-severe symptoms
• Comorbid conditions or immunocompromised state

The clavulanate component provides essential coverage against β-lactamase-producing Haemophilus influenzae (nearly 50% produce β-lactamase) and Moraxella catarrhalis (90-100% produce β-lactamase), while high-dose amoxicillin covers penicillin-resistant Streptococcus pneumoniae. 2, 4, 5 This combination achieves 90-92% predicted clinical efficacy against all major sinusitis pathogens. 2

Treatment duration: Continue for 5-10 days, or until symptom-free for 7 consecutive days (typically 10-14 days total). 1, 2 Recent evidence supports shorter 5-7 day courses with comparable efficacy and fewer adverse effects. 1, 2

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Penicillin Allergy

Second-generation cephalosporins: 1, 2

• Cefuroxime-axetil (standard dosing for 10 days)

Third-generation cephalosporins: 1, 2

• Cefpodoxime-proxetil (standard dosing for 10 days)
• Cefdinir 300 mg twice daily for 10 days 2
• Cefprozil (standard dosing for 10 days) 1

The risk of cross-reactivity between penicillins and second/third-generation cephalosporins is negligible in non-severe allergies. 2

Severe (Type I/Anaphylactic) Penicillin Allergy

Respiratory fluoroquinolones (reserve for documented severe allergy): 2, 3

• Levofloxacin 500 mg once daily for 10-14 days (preferred)
• Moxifloxacin 400 mg once daily for 10 days

Fluoroquinolones achieve 90-92% predicted clinical efficacy with excellent coverage against multidrug-resistant S. pneumoniae and complete activity against β-lactamase-producing organisms. 2 However, they should be reserved specifically for severe β-lactam allergies or treatment failures to prevent resistance development. 2

Doxycycline 100 mg once daily for 10 days is an acceptable but suboptimal alternative, with only 77-81% predicted efficacy and limited activity against H. influenzae. 2

Alternatives for Resistant Streptococcus pneumoniae

If the patient has risk factors for drug-resistant S. pneumoniae (DRSP)—including recent antibiotic use, age >65, daycare exposure, or comorbidities—start with high-dose amoxicillin-clavulanate (2 g/125 mg twice daily) from the outset. 2, 3, 4

If initial standard-dose amoxicillin-clavulanate fails after 3-5 days, switch to: 2

• High-dose amoxicillin-clavulanate (2 g/125 mg twice daily), OR
• Respiratory fluoroquinolone (levofloxacin 500 mg daily or moxifloxacin 400 mg daily)

Fluoroquinolones provide superior coverage against DRSP with 100% microbiologic eradication rates for S. pneumoniae. 2

Critical Antibiotics to AVOID

Never use as first-line therapy: 2, 3

• Azithromycin/macrolides – 20-25% resistance rates for both S. pneumoniae and H. influenzae make these ineffective
• Trimethoprim-sulfamethoxazole – 50% resistance for S. pneumoniae, 27% for H. influenzae
• First-generation cephalosporins (cephalexin) – inadequate coverage against H. influenzae

Watchful Waiting as an Alternative

For adults with uncomplicated ABRS, watchful waiting without immediate antibiotics is an appropriate initial strategy when reliable follow-up can be assured. 1 Start antibiotics only if no improvement occurs by 7 days or symptoms worsen at any time. 1

The number needed to treat with antibiotics is 10-15 to achieve one additional cure at 7-15 days, as most patients improve spontaneously. 1

Essential Adjunctive Therapies

Add to all patients regardless of antibiotic choice: 1, 2, 3

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily) – reduce mucosal inflammation and improve symptom resolution (strong evidence from multiple RCTs)
• Saline nasal irrigation – provides symptomatic relief and removes mucus
• Analgesics (acetaminophen or ibuprofen) – for pain and fever

Treatment Monitoring and Reassessment

Reassess at 3-5 days: 2, 3

• If no improvement, switch to high-dose amoxicillin-clavulanate or respiratory fluoroquinolone
• If worsening at any time, immediately evaluate for complications (orbital cellulitis, meningitis, brain abscess)

Reassess at 7 days: 1, 2, 3

• If symptoms persist or worsen, reconfirm diagnosis and exclude complications
• Consider imaging (CT scan) only if complications suspected or alternative diagnosis likely
• Refer to otolaryngology if no improvement after 7 days of appropriate second-line therapy

Expected timeline: Most patients show noticeable improvement within 3-5 days, with complete resolution by 10-14 days. 2, 3

Common Pitfalls to Avoid

• Do not prescribe antibiotics for symptoms <10 days unless severe features are present (fever ≥39°C with purulent discharge for ≥3 consecutive days). 1, 3
• Do not use fluoroquinolones as first-line in patients without documented β-lactam allergies—this promotes antimicrobial resistance. 2
• Do not extend ineffective therapy beyond 3-5 days—early switching prevents treatment failure and complications. 2, 3
• Do not obtain imaging (X-ray or CT) for uncomplicated cases—reserve for suspected complications or alternative diagnoses. 1