Doxycycline for Cellulitis
Doxycycline should NOT be used as monotherapy for typical 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 must always be combined with a beta-lactam to ensure adequate streptococcal coverage. 1
MRSA Risk Factors Requiring Doxycycline:
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Known MRSA colonization or evidence of MRSA infection elsewhere 1
- Systemic inflammatory response syndrome (SIRS) 1
Correct Dosing When Indicated:
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam (such as cephalexin 500 mg four times daily) for 5 days if clinical improvement occurs 1
- Extension beyond 5 days only if symptoms have not improved 1
Why Doxycycline Monotherapy Fails
Beta-lactam monotherapy is successful in 96% of typical cellulitis cases, confirming that streptococci are the predominant pathogens. 1 Doxycycline's unreliable streptococcal coverage means treatment failure is highly likely when used alone. 1, 2
A randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole (another agent with poor streptococcal coverage, similar to doxycycline) to cephalexin provided no additional benefit in pure cellulitis without abscess or purulent drainage. 3 This reinforces that MRSA coverage is unnecessary in typical cases. 1
Preferred First-Line Treatment
For typical nonpurulent cellulitis, use beta-lactam monotherapy: 1
- Cephalexin 500 mg four times daily 1
- Dicloxacillin 250-500 mg every 6 hours 1
- Amoxicillin 1
- Treatment duration: 5 days if clinical improvement occurs 1
Alternative When MRSA Coverage is Needed
If MRSA risk factors are present, clindamycin 300-450 mg orally every 6 hours is superior to doxycycline combinations because it provides single-agent coverage for both streptococci and MRSA, avoiding the need for combination therapy. 1 However, clindamycin should only be used if local MRSA resistance rates are <10%. 1
Critical Pitfall to Avoid
Never use doxycycline as monotherapy for cellulitis. 1, 2 If a patient fails doxycycline monotherapy, the most likely explanation is inadequate streptococcal coverage, not MRSA resistance. 2 In this scenario, either add a beta-lactam to the doxycycline or switch to clindamycin monotherapy. 2
Special Populations
Children under 8 years: Never use doxycycline due to tooth discoloration and bone growth effects. 1
Pregnant women: Doxycycline is pregnancy category D and should be avoided. 1