Would I prescribe amoxicillin-clavulanate (amox-clav) and azithromycin 500mg once daily for 10 days?

Should You Prescribe Amoxicillin-Clavulanate and Azithromycin 500mg Once Daily for 10 Days?

No, you should not prescribe both amoxicillin-clavulanate and azithromycin together for 10 days, as this combination is not supported by any guideline and represents unnecessary dual antibiotic therapy that increases adverse effects without improving outcomes. 1, 2, 3

Why This Combination Is Not Recommended

Lack of Guideline Support for Dual Therapy

• No major guideline recommends combining amoxicillin-clavulanate with azithromycin for any common indication. 1
• The IDSA guidelines for streptococcal pharyngitis list these antibiotics as alternative monotherapy options, not combination therapy. 1
• For respiratory infections including acute bacterial rhinosinusitis, guidelines compare these agents head-to-head as single-agent alternatives, never recommending concurrent use. 1

Increased Risk Without Benefit

• Combining these antibiotics significantly increases gastrointestinal adverse effects (diarrhea occurs in 17-32% with amoxicillin-clavulanate alone and 6% with azithromycin alone). 4, 5
• Studies directly comparing azithromycin versus amoxicillin-clavulanate show comparable efficacy as monotherapy, with no rationale for combining them. 6, 7, 8
• The most recent pediatric bronchiectasis trial (2018) demonstrated azithromycin was non-inferior to amoxicillin-clavulanate, but actually resulted in longer exacerbation duration (14 vs 10 days, p=0.014). 9

Correct Prescribing Approach

For Streptococcal Pharyngitis

• First-line: Amoxicillin alone at 50 mg/kg once daily (max 1,000 mg) or 25 mg/kg twice daily (max 500 mg per dose) for 10 days. 1, 2
• Azithromycin is reserved for penicillin-allergic patients only at 12 mg/kg once daily (max 500 mg) for 5 days, not 10 days. 1
• Amoxicillin-clavulanate is indicated only for chronic carriers who failed first-line therapy, not as initial treatment. 1, 2

For Respiratory Tract Infections

• Acute bacterial rhinosinusitis: Amoxicillin-clavulanate alone for 10 days is appropriate if bacterial infection is confirmed. 1
• Community-acquired pneumonia in children: If atypical coverage is needed, use amoxicillin 90 mg/kg/day with azithromycin 10 mg/kg day 1, then 5 mg/kg/day for days 2-5 (total 5 days, not 10). 3

Critical Dosing Errors in Your Proposed Regimen

Azithromycin Duration Is Wrong

• Azithromycin for pharyngitis is dosed for 5 days, not 10 days. 1, 4
• The FDA-approved regimen is 500 mg once daily for 3 days for sinusitis or 5 days for pharyngitis. 4
• Extending azithromycin to 10 days increases resistance risk without improving efficacy. 1

Unnecessary Antibiotic Exposure

• Dual therapy promotes antimicrobial resistance without clinical benefit. 3
• The IDSA emphasizes using the shortest effective duration of antimicrobial therapy. 3

When Dual Therapy Might Be Considered (Rare Scenarios)

Community-Acquired Pneumonia with Atypical Coverage

• Only scenario where combining beta-lactam with macrolide is appropriate: Suspected atypical pathogens in CAP. 3
• Correct regimen: Amoxicillin 90 mg/kg/day divided twice daily PLUS azithromycin 10 mg/kg day 1, then 5 mg/kg once daily for 4 more days (5 days total). 3
• This is not amoxicillin-clavulanate, and azithromycin is still only 5 days. 3

Common Pitfalls to Avoid

• Do not prescribe antibiotics in combination without clear guideline support for that specific combination. 1
• Do not extend azithromycin beyond 5 days for respiratory infections (3 days for sinusitis, 5 days for pharyngitis/pneumonia). 1, 4
• Do not use amoxicillin-clavulanate as first-line for uncomplicated strep throat—it is reserved for treatment failures or chronic carriers. 1, 2
• Assess for penicillin allergy before prescribing: If true allergy exists, use azithromycin OR a cephalosporin, not both with amoxicillin-clavulanate. 1

What You Should Prescribe Instead

Choose ONE antibiotic based on the specific indication:

• For strep throat (no penicillin allergy): Amoxicillin 500 mg twice daily for 10 days. 1
• For strep throat (penicillin allergy): Azithromycin 500 mg once daily for 5 days. 1
• For acute bacterial sinusitis: Amoxicillin-clavulanate 875/125 mg twice daily for 10 days. 1
• For CAP requiring atypical coverage: Amoxicillin (not amox-clav) 1000 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 4 days. 3