Doxycycline for Cellulitis
Doxycycline should NOT be used as monotherapy for typical nonpurulent cellulitis because it lacks reliable activity against beta-hemolytic streptococci, which are the primary pathogens in most cases. 1
When Doxycycline is Appropriate
Doxycycline is only appropriate for cellulitis when specific MRSA risk factors are present, and even then it must be combined with a beta-lactam antibiotic to ensure adequate streptococcal coverage. 1
MRSA Risk Factors Requiring Doxycycline + Beta-Lactam Combination:
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Evidence of MRSA infection elsewhere or documented MRSA colonization 1
- Systemic inflammatory response syndrome (SIRS) 1
- Failure to respond to beta-lactam monotherapy 1
Dosing When Indicated:
- Adults: Doxycycline 100 mg orally twice daily PLUS a beta-lactam (such as cephalexin 500 mg four times daily) 1
- Children >8 years and <45 kg: Doxycycline 2 mg/kg/dose orally every 12 hours PLUS a beta-lactam 1
- Duration: 5 days if clinical improvement occurs; extend only if symptoms persist 1
Why Beta-Lactam Monotherapy is Preferred for Typical Cellulitis
Beta-lactam monotherapy is successful in 96% of typical cellulitis cases, making it the standard of care. 1 MRSA is an uncommon cause of typical nonpurulent cellulitis, even in high-prevalence settings. 1, 2
First-Line Beta-Lactam Options:
- Cephalexin, dicloxacillin, amoxicillin, or penicillin 1
- These provide adequate coverage for streptococci and methicillin-sensitive S. aureus, the predominant pathogens 1, 2
Critical Contraindications for Doxycycline
- Never use in children under 8 years of age due to tooth discoloration and bone growth effects 1
- Avoid in pregnancy (category D) 1
Alternative to Doxycycline When MRSA Coverage is Needed
Clindamycin monotherapy is superior to doxycycline combinations because it provides coverage for both streptococci and MRSA without requiring a second antibiotic. 1
- Clindamycin dosing: 300-450 mg orally three times daily for 5 days 1
- This avoids the need for combination therapy and simplifies the regimen 1
Common Pitfall to Avoid
The most common error is using doxycycline alone for typical cellulitis without adding a beta-lactam, which leaves streptococcal coverage inadequate and risks treatment failure. 1 The research evidence confirms that adding trimethoprim-sulfamethoxazole (another agent with poor streptococcal activity) to cephalexin provides no benefit in pure cellulitis without abscess. 3 This reinforces that MRSA coverage is unnecessary in typical cases, and when it is needed, the streptococcal coverage must remain intact. 1