What is the next appropriate antibiotic for acute bacterial rhinosinusitis in a patient allergic to amoxicillin, amoxicillin‑clavulanate (Augmentin), cephalexin (Cephulac), and unable to tolerate vancomycin, who is taking levothyroxine (Synthroid)?

Recommended Antibiotic for Acute Bacterial Rhinosinusitis with Multiple Allergies

For a patient with documented allergies to amoxicillin, Augmentin, cephalexin, and vancomycin who has failed azithromycin, prescribe levofloxacin 500 mg once daily for 10–14 days as the definitive next-step antibiotic. 1

Why Levofloxacin Is the Correct Choice

• Levofloxacin provides 90–92% predicted clinical efficacy against the three major sinusitis pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), including multidrug-resistant strains. 1

• Respiratory fluoroquinolones (levofloxacin or moxifloxacin) are the guideline-recommended first-line agents for patients with severe penicillin allergy who cannot receive β-lactam antibiotics. 1, 2

• Your patient's allergy profile eliminates all β-lactam options: amoxicillin, Augmentin, and cephalexin are all contraindicated due to documented allergies. 1

• Azithromycin has already failed, and macrolides have 20–25% resistance rates for S. pneumoniae and H. influenzae, making them unsuitable for empiric therapy. 1, 3

Dosing and Duration

• Standard regimen: levofloxacin 500 mg orally once daily for 10–14 days (or until symptom-free for 7 consecutive days, typically resulting in a 10–14 day total course). 1, 4

• Alternative high-dose short-course: levofloxacin 750 mg once daily for 5 days is FDA-approved and non-inferior to the 10-day 500 mg regimen, though the 10–14 day course is more commonly recommended in guidelines. 4

Why Other Options Are Inappropriate

Doxycycline

• Doxycycline has only 77–81% predicted efficacy with a 20–25% bacteriologic failure rate due to limited activity against H. influenzae. 1
• Doxycycline should be reserved only when fluoroquinolones are contraindicated (e.g., pregnancy, tendon disorders, QT-prolongation risk). 1

Clindamycin

• Clindamycin lacks activity against H. influenzae and M. catarrhalis, two of the three most common bacterial pathogens in acute sinusitis. 1
• Clindamycin monotherapy will fail in approximately 30–40% of acute bacterial sinusitis cases. 1
• If clindamycin is used, it must be combined with a third-generation cephalosporin (cefixime or cefpodoxime), but your patient is allergic to cephalexin, raising concern about cross-reactivity. 1

Trimethoprim-Sulfamethoxazole (Bactrim)

• Bactrim has 50% resistance in S. pneumoniae and 27% resistance in H. influenzae, making it unsuitable for empiric therapy. 1

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1

• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1

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

Monitoring and Reassessment Protocol

• Reassess at 3–5 days: If no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), this signals treatment failure and requires urgent ENT referral, sinus cultures (direct aspiration or endoscopic sampling), and CT imaging to exclude complications. 1

• Reassess at 7 days: By this point, most patients should show significant improvement. Persistent or worsening symptoms mandate diagnostic reconsideration, exclusion of complications (orbital cellulitis, meningitis, intracranial abscess), and specialist referral. 1

Red-Flag Situations Requiring Urgent ENT Referral

• No clinical improvement after 7 days of appropriate levofloxacin therapy. 1, 2

• Any worsening of symptoms at any time (increasing facial pain, fever, purulent drainage). 1, 2

• Signs of complications: severe headache, visual changes, periorbital swelling/erythema, proptosis, diplopia, altered mental status, or cranial nerve deficits. 1, 2

• Recurrent sinusitis (≥3 episodes per year) suggesting underlying allergic rhinitis, immunodeficiency, or anatomic abnormality. 1, 2

Critical Pitfalls to Avoid

• Do not extend azithromycin or try another macrolide—resistance rates are too high (20–25%) and your patient has already failed azithromycin. 1, 3

• Do not use doxycycline as first-line when levofloxacin is available; doxycycline has inferior efficacy (77–81% vs. 90–92%). 1

• Ensure a minimum 10-day treatment duration to prevent relapse and resistance development. 1

• Fluoroquinolone-associated risks must be discussed: tendon rupture (especially >60 years, concurrent corticosteroids, or renal disease), QT-interval prolongation, and photosensitivity. 1

Alternative If Fluoroquinolones Are Contraindicated

• If levofloxacin is contraindicated (e.g., pregnancy, history of tendon rupture, severe QT prolongation), consider combination therapy with clindamycin plus a third-generation cephalosporin (cefixime or cefpodoxime). 1

• However, confirm the type of cephalexin allergy first—if it was a severe Type I reaction, all cephalosporins should be avoided. 1

• For non-severe cephalexin allergy (e.g., mild rash), second- or third-generation cephalosporins with dissimilar side chains can be used safely. 1