Doxycycline Dosing for Cellulitis
For uncomplicated cellulitis in adults, doxycycline 100 mg orally twice daily for 5 days is the recommended dosage, but ONLY when combined with a beta-lactam antibiotic, as doxycycline alone lacks reliable activity against beta-hemolytic streptococci, the primary pathogens in typical cellulitis. 1, 2
Critical Decision Point: When Doxycycline Is Appropriate
Doxycycline should ONLY be used for cellulitis when specific MRSA risk factors are present:
- Purulent drainage or exudate 1
- Penetrating trauma or injection drug use 1
- Evidence of MRSA infection elsewhere or known MRSA colonization 1
- Systemic inflammatory response syndrome (SIRS) 1
For typical nonpurulent cellulitis WITHOUT these risk factors, beta-lactam monotherapy (cephalexin, dicloxacillin, or amoxicillin) is the standard of care with a 96% success rate, and doxycycline is NOT indicated. 1
Mandatory Combination Therapy
Doxycycline MUST be combined with a beta-lactam when treating cellulitis because tetracyclines have unreliable activity against beta-hemolytic streptococci. 1
Recommended combination regimens:
- Doxycycline 100 mg orally twice daily PLUS cephalexin 500 mg orally four times daily 1
- Doxycycline 100 mg orally twice daily PLUS amoxicillin 500 mg orally three times daily 1
Standard Adult Dosing
The FDA-approved dosing for doxycycline is 200 mg on the first day (100 mg every 12 hours), followed by 100 mg daily as maintenance. 2 However, for skin and soft tissue infections including cellulitis, the standard regimen is 100 mg orally twice daily (every 12 hours) for the entire treatment course. 3, 2
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, and erythema). 1, 4 Extend treatment ONLY if symptoms have not improved within this 5-day timeframe. 1, 4
Do NOT reflexively extend to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication. 1
Pediatric Dosing
For children ≥8 years weighing <45 kg: 2 mg/kg/dose orally every 12 hours 3
For children ≥8 years weighing ≥45 kg: Use adult dose of 100 mg orally twice daily 3
NEVER use doxycycline in children <8 years due to tooth discoloration and bone growth effects. 1
Absolute Contraindications
Pregnancy (Category D): Doxycycline is contraindicated in pregnant women. 1
Children <8 years: Risk of permanent tooth discoloration and impaired bone development. 1
When Doxycycline Monotherapy Is NEVER Appropriate
Do NOT use doxycycline as monotherapy for typical nonpurulent cellulitis. 1 Streptococcal coverage will be inadequate, leading to treatment failure. 1
Alternative single-agent options that cover both streptococci and MRSA:
- Clindamycin 300-450 mg orally every 6 hours (if local MRSA resistance <10%) 1
- Linezolid 600 mg orally twice daily (expensive, reserve for complicated cases) 1
Clinical Reassessment
Mandatory reassessment within 24-48 hours to verify clinical response. 1 Treatment failure rates of 21% have been reported with some oral regimens. 1
If no improvement or worsening after 48 hours:
- Consider resistant organisms (MRSA) 1
- Evaluate for deeper infection or abscess requiring drainage 1
- Assess for necrotizing fasciitis (severe pain out of proportion, skin anesthesia, rapid progression) 1
- Switch to vancomycin 15-20 mg/kg IV every 8-12 hours if systemic toxicity present 1
Common Pitfall to Avoid
The most common error is using doxycycline alone for typical cellulitis without adding a beta-lactam. 1 This results in inadequate streptococcal coverage and predictable treatment failure. 1 Always combine doxycycline with cephalexin, amoxicillin, or use clindamycin monotherapy instead. 1