What antibiotic can I use for a patient with cellulitis who is on warfarin (anticoagulant)?

Antibiotic Selection for Cellulitis in Patients on Warfarin

For a patient with cellulitis on warfarin, use cephalexin 500 mg orally four times daily for 5 days, as it provides excellent streptococcal coverage without significant warfarin interaction risk. 1, 2

First-Line Antibiotic Choice

• Cephalexin is the preferred first-line agent for uncomplicated cellulitis, targeting streptococci (the primary pathogen in typical cellulitis) and methicillin-sensitive Staphylococcus aureus 1, 2
• The standard dose is 500 mg orally four times daily for 5 days 2
• Cephalosporins like cephalexin have minimal documented interaction with warfarin, though one case report exists with ceftaroline (a different cephalosporin) showing INR elevation 3

Antibiotics to AVOID in Warfarin Patients

• Clarithromycin should be avoided as it significantly potentiates warfarin effects, requiring careful prothrombin time monitoring if used 4
• Doxycycline requires caution as tetracyclines have been shown to depress plasma prothrombin activity, potentially requiring downward adjustment of anticoagulant dosage 5
• Trimethoprim-sulfamethoxazole also interacts with warfarin and should be avoided unless MRSA coverage is specifically indicated 5

Alternative Options if Cephalexin Cannot Be Used

• Clindamycin 300-450 mg orally four times daily for 5 days is the best alternative, particularly for penicillin/cephalosporin-allergic patients 6, 2
• Clindamycin provides excellent streptococcal coverage and does not have significant warfarin interactions 6
• Penicillin VK or amoxicillin are also reasonable alternatives with minimal warfarin interaction concerns 1, 2

When to Consider MRSA Coverage (Despite Warfarin)

MRSA coverage is only indicated in specific high-risk situations 1, 2:

• Penetrating trauma associated with the cellulitis
• Evidence of MRSA infection elsewhere or known nasal colonization
• Purulent drainage present
• Injection drug use history
• Systemic inflammatory response syndrome (SIRS) present

If MRSA coverage is required in a warfarin patient, clindamycin alone is the safest choice, as it covers both streptococci and MRSA without warfarin interaction 6, 2

Critical Monitoring Considerations

• If you must use an antibiotic with warfarin interaction potential (clarithromycin, doxycycline, or trimethoprim-sulfamethoxazole), prothrombin time/INR must be carefully monitored 4, 5
• Standard beta-lactam therapy (cephalexin) is successful in 96% of typical cellulitis cases, making MRSA coverage unnecessary in most patients 2
• Treatment duration is 5 days if clinical improvement occurs; extend only if no improvement within this timeframe 1, 6

Adjunctive Measures

• Elevate the affected extremity to promote drainage 1, 6, 2
• Examine and treat interdigital toe spaces for tinea pedis or maceration, as this reduces recurrence risk 1, 6
• Address underlying predisposing factors such as venous insufficiency or lymphedema 1, 2