What is the appropriate first‑line oral antibiotic for acute bacterial sinusitis in a patient allergic to erythromycin (macrolide) and trimethoprim‑sulfamethoxazole (Bactrim), without a penicillin allergy and with normal renal and hepatic function?

Antibiotic Options for Acute Bacterial Sinusitis with Erythromycin and Bactrim Allergy

For a patient allergic to erythromycin (macrolide) and Bactrim but without penicillin allergy, amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days is the clear first-line choice. 1

First-Line Treatment: Amoxicillin-Clavulanate

• Amoxicillin-clavulanate (Augmentin) 875 mg/125 mg twice daily for 5-10 days is the preferred first-line antibiotic for acute bacterial sinusitis in adults without penicillin allergy, achieving 90-92% predicted clinical efficacy against the major pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). 1

• The clavulanate component is critical because 30-40% of H. influenzae and 90-100% of M. catarrhalis produce β-lactamase, rendering plain amoxicillin ineffective against these organisms. 1

• Treatment duration should be 5-10 days or until symptom-free for 7 consecutive days (typically 10-14 days total), with recent evidence supporting shorter 5-7 day courses as equally effective with fewer adverse effects. 1

Why Your Allergies Don't Eliminate This Option

• Your erythromycin (macrolide) allergy does NOT contraindicate amoxicillin-clavulanate—these are completely different drug classes with no cross-reactivity. 1

• Your Bactrim (trimethoprim-sulfamethoxazole) allergy also does NOT contraindicate amoxicillin-clavulanate—again, entirely different mechanisms and structures. 1

• Macrolides (erythromycin, azithromycin, clarithromycin) should be avoided anyway due to resistance rates exceeding 20-25% for both S. pneumoniae and H. influenzae, making them unsuitable for sinusitis regardless of allergy status. 1

• Bactrim itself is inappropriate for sinusitis due to 50% resistance in S. pneumoniae and 27% resistance in H. influenzae. 1

Confirming Bacterial Sinusitis Before Treatment

Before prescribing antibiotics, confirm you meet at least one of these three criteria for acute bacterial rhinosinusitis: 1

• Persistent symptoms ≥10 days without improvement (purulent nasal discharge with nasal obstruction or facial pain/pressure)
• Severe symptoms for ≥3-4 consecutive days (fever ≥39°C with purulent nasal discharge)
• "Double sickening"—worsening after initial improvement from a viral upper respiratory infection

Remember that 98-99.5% of acute rhinosinusitis is viral and resolves spontaneously within 7-10 days without antibiotics. 1

High-Dose Regimen for Specific Risk Factors

Use high-dose amoxicillin-clavulanate (2 g/125 mg twice daily) if you have any of these risk factors: 1

• Recent antibiotic use within the past 4-6 weeks
• Age >65 years
• Moderate-to-severe symptoms
• Comorbid conditions (diabetes, COPD, immunosuppression)

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily—strongly recommended to reduce mucosal inflammation and improve symptom resolution, backed by multiple randomized controlled trials. 1

• Saline nasal irrigation 2-3 times daily for symptomatic relief and mucus clearance. 1

• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1

Monitoring and When to Switch Antibiotics

• Reassess at 3-5 days: If no improvement, switch to a respiratory fluoroquinolone (levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10 days). 1

• Reassess at 7 days: If symptoms persist or worsen, reconfirm the diagnosis and consider complications (orbital cellulitis, meningitis) or alternative diagnoses. 1

• Expect noticeable improvement within 3-5 days of starting appropriate therapy, with complete resolution typically by 10-14 days. 1

Alternative Options (Only If Amoxicillin-Clavulanate Fails or Is Not Tolerated)

If you cannot tolerate amoxicillin-clavulanate (e.g., severe gastrointestinal side effects, which occur in 40-43% of patients): 1

• Respiratory fluoroquinolones (levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10 days) provide 90-92% efficacy and excellent coverage of multidrug-resistant organisms. 1, 2

• Doxycycline 100 mg once daily for 10 days is an acceptable but suboptimal alternative with 77-81% predicted efficacy and limited activity against H. influenzae. 1

Critical Pitfalls to Avoid

• Do not use macrolides (azithromycin, clarithromycin, erythromycin) as first-line therapy—resistance rates make treatment failure likely, and your erythromycin allergy already excludes this class. 1

• Do not prescribe antibiotics for symptoms <10 days unless severe features are present (fever ≥39°C with purulent discharge for ≥3 consecutive days). 1

• Do not obtain routine imaging (X-ray or CT) for uncomplicated acute bacterial sinusitis—reserve imaging for suspected complications or alternative diagnoses. 1

• Gastrointestinal side effects are common with amoxicillin-clavulanate (diarrhea in 40-43%, severe diarrhea in 7-8%)—taking it with food may reduce this. 1

When to Refer to ENT

Refer to otolaryngology if: 1

• No improvement after 7 days of appropriate second-line antibiotic therapy
• Worsening symptoms at any time
• Suspected complications (severe headache, visual changes, periorbital swelling, altered mental status)
• Recurrent sinusitis (≥3 episodes per year)