Doxycycline Dosing for Cellulitis
For typical nonpurulent cellulitis, doxycycline should NEVER be used as monotherapy—it must be combined with a beta-lactam (e.g., cephalexin or amoxicillin) because doxycycline lacks reliable activity against beta-hemolytic streptococci, which cause the vast majority of cellulitis cases. 1, 2
When Doxycycline Is Appropriate
Doxycycline is indicated only when MRSA coverage is needed, specifically in these scenarios:
- Purulent cellulitis with visible drainage or exudate 1, 2
- Penetrating trauma or injection drug use 1, 2
- Known MRSA colonization or prior MRSA infection 2
- Systemic inflammatory response syndrome (SIRS) present 2
- Failure to respond to beta-lactam therapy after 48-72 hours 2
For typical nonpurulent cellulitis without these risk factors, beta-lactam monotherapy achieves 96% success rates, making MRSA coverage unnecessary. 1, 2
Dosing Regimens
For Purulent Cellulitis (MRSA Coverage Needed)
Doxycycline 100 mg orally twice daily for 5 days as monotherapy is appropriate when purulent drainage is present. 2, 3 Extend treatment only if warmth, tenderness, or erythema have not improved within this timeframe. 2
For Nonpurulent Cellulitis Requiring MRSA Coverage
Combination therapy is mandatory: Doxycycline 100 mg orally twice daily PLUS a beta-lactam (cephalexin 500 mg four times daily OR amoxicillin 500 mg three times daily) for 5 days. 1, 2 This combination provides both streptococcal and MRSA coverage.
For Severe Infections Requiring IV Therapy
Doxycycline 100 mg IV every 12 hours can be used, but must be combined with vancomycin 15-20 mg/kg IV every 8-12 hours for adequate MRSA and streptococcal coverage in hospitalized patients. 1, 3
Absolute Contraindications
- Children younger than 8 years: Risk of permanent tooth discoloration and impaired bone growth 1, 2, 3
- Pregnant women: Pregnancy category D; fetal risk 1, 2
Critical Pitfalls to Avoid
Never use doxycycline alone for typical cellulitis—this misses streptococcal pathogens in 96% of cases and represents a fundamental treatment error. 1, 2 Some streptococcal strains possess intrinsic tetracycline resistance, further limiting doxycycline's utility. 1
Do not reflexively add MRSA coverage to all cellulitis cases simply because MRSA exists in your community—MRSA is an uncommon cause of typical nonpurulent cellulitis even in high-prevalence settings. 1, 2
Alternative Regimens for Penicillin Allergy
If the patient cannot take beta-lactams and requires MRSA coverage, 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. 1, 2 However, clindamycin should only be used if local MRSA clindamycin resistance rates are ≤10%. 1, 2
Treatment Duration Evidence
The 5-day duration is supported by high-quality randomized controlled trial evidence showing no difference in outcomes between 5-day and 10-day courses for uncomplicated cellulitis. 2, 4 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1, 2