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 combined with a beta-lactam antibiotic in specific clinical scenarios requiring MRSA coverage: 1
- Purulent cellulitis with drainage or exudate 1
- Penetrating trauma or injection drug use 1
- Known MRSA colonization or infection elsewhere 1
- Systemic inflammatory response syndrome (SIRS) 1
Dosing When Indicated
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam (such as cephalexin) for 5 days if clinical improvement occurs 1
- Extension beyond 5 days only if symptoms have not improved 1
Why Doxycycline Fails as Monotherapy
Beta-hemolytic streptococci cause 96% of typical nonpurulent cellulitis, and doxycycline's activity against these organisms is unreliable and inconsistent. 1, 2 This explains why patients on doxycycline monotherapy frequently experience treatment failure—not because of MRSA resistance, but because of inadequate streptococcal coverage. 2
Preferred First-Line Treatment
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate: 1
- Cephalexin (oral)
- Dicloxacillin (oral)
- Amoxicillin (oral)
- Cefazolin (IV for hospitalized patients)
These agents provide excellent coverage against streptococci and methicillin-sensitive Staphylococcus aureus without the need for MRSA coverage in typical cases. 1, 3
When to Add MRSA Coverage
MRSA is an uncommon cause of typical cellulitis, even in high-prevalence settings. 1 Add MRSA-active therapy ONLY when specific risk factors are present:
- Purulent drainage or exudate 1
- Penetrating trauma or injection drug use 1
- Evidence of MRSA infection elsewhere 1
- Failure of beta-lactam therapy after 48 hours 1
Preferred MRSA-Active Regimens
If MRSA coverage is needed, choose ONE of these options:
- Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
- Doxycycline 100 mg twice daily PLUS cephalexin 1
- Trimethoprim-sulfamethoxazole PLUS a beta-lactam 1
Critical Pitfalls to Avoid
- Never use doxycycline alone for typical nonpurulent cellulitis—streptococcal coverage will be inadequate 1, 2
- Do not reflexively add MRSA coverage to all cellulitis cases, as this represents overtreatment and increases antibiotic resistance 1
- Reassess at 24-48 hours to verify clinical response, as treatment failure may indicate resistant organisms or misdiagnosis 1
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 Traditional 7-14 day courses are unnecessary for uncomplicated cases. 1