What's the next step for a patient with leg cellulitis who hasn't improved on doxycycline (doxy) after 8 days, despite being ambulatory and not elevating the affected leg?

Switch Antibiotics Immediately and Address Mobility Issues

For a patient with leg cellulitis failing doxycycline after 8 days, you must switch to an antibiotic with reliable streptococcal coverage—either add a beta-lactam (cephalexin 500mg four times daily) to the current doxycycline, or switch to clindamycin monotherapy (300-450mg three times daily)—and mandate strict leg elevation. 1

Why Doxycycline is Failing

• Doxycycline lacks consistent coverage for beta-hemolytic streptococci, which are the predominant pathogens in typical non-purulent cellulitis. 1 This unreliable streptococcal activity is the most likely reason for treatment failure, not MRSA resistance. 1

• The constant movement and failure to elevate the leg is compounding the problem by preventing drainage of edema, which is essential for resolution. 2, 1

Immediate Antibiotic Adjustment Algorithm

Step 1: Assess for features requiring hospitalization 1

• Fever, hypotension, altered mental status, or systemic inflammatory response syndrome (SIRS) → hospitalize and start IV vancomycin 1
• If stable for outpatient management, proceed to Step 2

Step 2: Evaluate for MRSA risk factors 1

• Purulent drainage or exudate 2
• Penetrating trauma or injection drug use 1
• Known MRSA colonization or previous MRSA infection 2
• If MRSA features present: Continue doxycycline AND add cephalexin 500mg PO four times daily for dual coverage 1
• If no MRSA features: Switch to clindamycin 300-450mg PO three times daily as monotherapy 2, 1

Step 3: Treatment duration 1

• Treat for 5 days if clinical improvement occurs 3, 1
• Reassess at 48-72 hours to determine treatment response 1, 4
• Extend treatment if no improvement by day 5 1

Critical Non-Pharmacologic Intervention

Leg elevation is non-negotiable and must be enforced. 2, 1 The patient's constant movement is preventing edema drainage, which is as important as antibiotic selection for cellulitis resolution. 2

• Instruct strict bed rest with leg elevated above heart level 2, 1
• If compliance is an issue, consider short-term hospitalization for supervised elevation and IV antibiotics 1

Address Predisposing Factors

• Examine for and treat tinea pedis (athlete's foot), which creates portals of entry for bacteria 2, 1
• Assess for venous insufficiency, lymphedema, or obesity 1
• Treat any underlying venous eczema or skin breakdown 2

Common Pitfalls to Avoid

• Do not continue doxycycline monotherapy for typical cellulitis—streptococcal coverage is inadequate. 1
• Do not assume treatment failure automatically means MRSA—inadequate streptococcal coverage is far more likely. 1
• Do not prescribe antibiotics without addressing leg elevation—the mechanical component of treatment is essential. 2, 1
• MRSA is actually an unusual cause of typical non-purulent cellulitis; treatment failure with doxycycline strongly suggests inadequate streptococcal coverage rather than MRSA resistance. 1

When to Hospitalize

Consider admission if: 1

• Systemic signs of infection (fever, hypotension, altered mental status)
• Patient cannot comply with leg elevation at home
• Failure to improve after 48-72 hours of appropriate outpatient therapy
• Severe infection requiring IV antibiotics (vancomycin 15-20mg/kg IV every 8-12 hours) 1