In an adult with a skin or soft‑tissue infection, does doxycycline cover Staphylococcus aureus (including MSSA and MRSA) and what is the recommended dosing regimen?

Doxycycline Coverage for Staphylococcus aureus

Doxycycline has unreliable activity against beta-hemolytic streptococci and should never be used as monotherapy for typical cellulitis, but it does provide reasonable coverage for MRSA in skin and soft tissue infections when combined with a beta-lactam. 1

Coverage Spectrum and Limitations

MRSA Coverage

• Doxycycline demonstrates good in vitro activity against community-acquired MRSA strains, with approximately 95% susceptibility rates in most regions 2
• For purulent cellulitis requiring MRSA coverage, doxycycline 100 mg orally twice daily is an appropriate option when combined with a beta-lactam 3
• Doxycycline is specifically recommended by IDSA guidelines for cellulitis associated with penetrating trauma, purulent drainage, or MRSA risk factors—but only in combination therapy 1

Critical Gap: Streptococcal Coverage

• Doxycycline lacks reliable activity against beta-hemolytic streptococci (particularly Streptococcus pyogenes), which are the primary pathogens in typical nonpurulent cellulitis 1, 3
• The IDSA explicitly states that tetracyclines should not be used as monotherapy for typical cellulitis because streptococcal coverage is inadequate 3
• Some streptococcal strains demonstrate intrinsic resistance to tetracyclines 1

MSSA Coverage

• While doxycycline shows in vitro susceptibility against many MSSA strains, clinical data supporting its effectiveness for MSSA infections is limited compared to beta-lactams 4
• Beta-lactams (penicillinase-resistant penicillins or first-generation cephalosporins) remain superior choices for documented MSSA infections 5

Recommended Dosing Regimens

Standard Adult Dosing

• Doxycycline 100 mg orally twice daily for 5 days if clinical improvement occurs, extending only if symptoms persist 3
• For severe infections requiring IV therapy: doxycycline 100 mg IV every 12 hours 1

Pediatric Dosing

• Children ≥8 years and <45 kg: 2 mg/kg/dose orally every 12 hours 3
• Never use doxycycline in children <8 years due to tooth discoloration and bone growth effects 1, 3

Combination Therapy Requirements

• For typical nonpurulent cellulitis: doxycycline MUST be combined with a beta-lactam (cephalexin, dicloxacillin, or amoxicillin) to ensure adequate streptococcal coverage 3
• For purulent cellulitis with MRSA risk factors: doxycycline plus cephalexin or dicloxacillin 1, 3

Clinical Decision Algorithm

When Doxycycline Is Appropriate

1. Purulent cellulitis with visible drainage or exudate (MRSA coverage needed) 1, 3
2. Penetrating trauma or injection drug use (MRSA risk factor present) 1, 3
3. Known MRSA colonization or infection elsewhere 3
4. Patient has penicillin allergy but can tolerate cephalosporins (use doxycycline + cephalexin) 3

When Doxycycline Is NOT Appropriate

1. Typical nonpurulent cellulitis as monotherapy (will miss streptococci) 1, 3
2. Children <8 years of age (tooth/bone toxicity) 1, 3
3. Pregnant women (pregnancy category D) 3
4. When clindamycin is available and local MRSA resistance <10% (clindamycin provides single-agent coverage for both streptococci and MRSA) 3

Evidence Quality Considerations

Minocycline vs. Doxycycline

• Minocycline demonstrates superior clinical effectiveness compared to doxycycline for MRSA skin infections, with more reliable eradication rates 6, 7
• For MRSA, in vitro susceptibilities do not always predict in vivo effectiveness, and minocycline is more reliably effective than doxycycline when TMP-SMX or doxycycline fails 6
• Minocycline cannot be substituted with doxycycline for MRSA CNS infections 7

Clinical Outcomes Data

• Retrospective cohort data shows doxycycline/minocycline treatment resulted in significantly lower failure rates compared to beta-lactam monotherapy for community-acquired MRSA skin infections (adjusted OR for beta-lactam failure: 3.94) 2
• Treatment failure rates of 21% have been reported with some oral regimens, mandating reassessment within 24-48 hours 3

Common Pitfalls to Avoid

1. Never use doxycycline alone for typical cellulitis—this is the most common error, as it will miss streptococcal pathogens that cause 96% of typical cellulitis cases 1, 3
2. Do not assume doxycycline and minocycline are interchangeable—minocycline has superior clinical effectiveness for MRSA 6, 7
3. Do not reflexively add MRSA coverage to all cellulitis cases—MRSA is uncommon in typical nonpurulent cellulitis even in high-prevalence settings 3
4. Avoid doxycycline in pregnancy and young children—use clindamycin or TMP-SMX plus beta-lactam instead 1, 3