What is the recommended doxycycline dose, duration, and administration instructions for an adult with uncomplicated acute cellulitis when community‑acquired methicillin‑resistant Staphylococcus aureus is a possible etiology?

Doxycycline Dosing for Cellulitis with Possible CA-MRSA

For uncomplicated acute cellulitis when CA-MRSA is a possible etiology, doxycycline 100 mg orally twice daily for 5 days must be combined with a beta-lactam (cephalexin 500 mg four times daily or amoxicillin 500 mg three times daily) because doxycycline alone lacks reliable activity against beta-hemolytic streptococci, which cause the vast majority of typical cellulitis cases. 1

When Doxycycline Combination Therapy Is Appropriate

Add MRSA coverage with doxycycline plus a beta-lactam only when specific risk factors are present:

• Purulent drainage or exudate at the infection site 1
• Penetrating trauma or injection drug use 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min) 1
• Failure to respond to beta-lactam monotherapy after 48–72 hours 1

In the absence of these risk factors, beta-lactam monotherapy achieves 96% clinical success, making MRSA coverage unnecessary and representing overtreatment. 1

Exact Dosing Regimen

Combination Therapy (Non-Purulent Cellulitis with MRSA Risk Factors)

• Doxycycline 100 mg orally twice daily 1
• PLUS cephalexin 500 mg orally four times daily 1
• OR amoxicillin 500 mg orally three times daily 1
• Duration: 5 days if clinical improvement occurs (warmth and tenderness resolved, erythema improving, patient afebrile); extend only if symptoms have not improved 1

Monotherapy (Purulent Cellulitis with Visible Drainage)

• Doxycycline 100 mg orally twice daily for 5 days as monotherapy is appropriate when purulent drainage is present 1

Severe Infections Requiring IV Therapy

• Doxycycline 100 mg IV every 12 hours combined with vancomycin 15–20 mg/kg IV every 8–12 hours for hospitalized patients with systemic toxicity 1

Absolute Contraindications

• Children younger than 8 years – risk of permanent tooth discoloration and impaired bone growth 1
• Pregnant women – pregnancy category D with fetal risk 1

Critical Pitfalls to Avoid

Never use doxycycline as monotherapy for typical non-purulent cellulitis. This fundamental error misses streptococcal pathogens in approximately 96% of cases, and some streptococcal strains possess intrinsic tetracycline resistance. 1 Doxycycline lacks reliable activity against beta-hemolytic streptococci, which are the primary pathogens in typical cellulitis. 1

Do not reflexively add MRSA coverage to all cellulitis cases. MRSA is an uncommon cause of typical non-purulent cellulitis even in high-prevalence settings. 1 Adding MRSA coverage without specific risk factors increases antibiotic resistance without improving outcomes. 1

Alternative Regimen for Penicillin Allergy

When beta-lactams cannot be used and MRSA coverage is needed, clindamycin 300–450 mg orally every 6 hours is preferred over doxycycline because it provides single-agent coverage of both streptococci and MRSA, eliminating the need for combination therapy—but only if local MRSA clindamycin resistance rates are ≤10%. 1

Pediatric Dosing (Children ≥8 Years)

• Doxycycline 2 mg/kg per dose orally every 12 hours (maximum 100 mg per dose) 1
• MUST be combined with a beta-lactam (cephalexin 25–50 mg/kg/day divided every 6 hours) for non-purulent cellulitis 1
• Weight restriction: <45 kg 1

Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances 1
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration; treating these eradicates colonization and reduces recurrent infection 1
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema 1

Evidence Quality

The 2011 Infectious Diseases Society of America guidelines assign an A-II level (strong recommendation, moderate-quality evidence) to the use of doxycycline for outpatient MRSA coverage in skin and soft-tissue infections. 1 High-quality randomized controlled trial evidence shows that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis; traditional 7–14-day regimens are no longer necessary. 1