In an otherwise healthy adult with persistent sinusitis, can amoxicillin‑clavulanate (Augmentin) be combined with levofloxacin?

Can Augmentin and Levofloxacin Be Combined for Persistent Sinusitis?

No, you should not combine amoxicillin-clavulanate (Augmentin) and levofloxacin for persistent sinusitis—instead, switch from Augmentin to levofloxacin as monotherapy when first-line treatment fails. 1

Why Combination Therapy Is Not Recommended

• Guidelines explicitly recommend switching antibiotics rather than adding a second agent when initial therapy fails after 3–5 days of treatment. 1, 2
• No evidence supports dual antibiotic therapy for uncomplicated acute bacterial sinusitis; all major guidelines (American Academy of Otolaryngology–Head and Neck Surgery, IDSA, European Position Paper) recommend sequential monotherapy rather than combination regimens. 1
• Combining antibiotics increases adverse effects without improving outcomes—amoxicillin-clavulanate already causes diarrhea in 40–43% of patients, and adding levofloxacin would compound gastrointestinal side effects and other fluoroquinolone-associated risks (tendon rupture, QT prolongation). 1, 2

The Correct Approach: Sequential Monotherapy

When to Switch from Augmentin

• Reassess at 3–5 days: If purulent nasal discharge persists, facial pain/pressure is unchanged, or symptoms worsen, this constitutes treatment failure requiring immediate switch to second-line therapy. 1, 2
• Do not wait beyond 3–5 days to change therapy in non-responders; delayed escalation increases complication risk and prolongs ineffective treatment. 1, 2

Second-Line Regimen After Augmentin Failure

• Levofloxacin 500 mg orally once daily for 10–14 days (or until symptom-free for 7 consecutive days) provides 90–92% predicted clinical efficacy against drug-resistant Streptococcus pneumoniae and β-lactamase-producing Haemophilus influenzae. 1, 3
• Moxifloxacin 400 mg orally once daily for 10 days offers equivalent efficacy (90–92%) and may improve compliance with once-daily dosing. 1, 3
• Stop Augmentin when starting the fluoroquinolone—there is no role for continuing both antibiotics simultaneously. 1, 2

Why Levofloxacin Works After Augmentin Fails

• Fluoroquinolones cover β-lactamase-producing organisms (H. influenzae, Moraxella catarrhalis) that may have caused Augmentin failure, while retaining excellent activity against penicillin-resistant and multidrug-resistant S. pneumoniae. 1, 3
• Levofloxacin and amoxicillin-clavulanate showed comparable efficacy (88.4% vs 87.3% clinical success) in head-to-head trials, but levofloxacin had significantly fewer adverse effects (7.4% vs 21.2%). 4, 5

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily markedly reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1, 2
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1, 2
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1, 2

Monitoring After Switching to Levofloxacin

• Reassess at 3–5 days after switching: Persistent lack of improvement signals treatment failure and requires ENT referral, sinus cultures (direct aspiration or endoscopic sampling), and CT imaging to exclude complications. 1, 2
• By day 7 of levofloxacin, most patients should show significant improvement; ongoing or worsening symptoms mandate diagnostic reconsideration, exclusion of complications (orbital cellulitis, meningitis, intracranial abscess), and specialist referral. 1, 2

Red-Flag Situations Requiring Urgent ENT Referral

• No clinical improvement after 7 days of appropriate levofloxacin therapy. 1, 2
• Any worsening of symptoms (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 Augmentin beyond 3–5 days without improvement—early discontinuation prevents unnecessary exposure and bacterial proliferation. 1, 2
• Do not combine antibiotics—guidelines universally recommend switching, not adding. 1, 2
• Ensure minimum 10-day levofloxacin duration to prevent relapse and resistance development. 1, 2
• Reserve fluoroquinolones appropriately: after Augmentin failure they become the next step rather than being held in reserve. 1, 3