Antimicrobial Coverage Comparison: Cephalexin vs Doxycycline vs Bactrim
For typical skin and soft tissue infections, cephalexin provides superior coverage against the most common pathogens (streptococci and methicillin-susceptible Staphylococcus aureus), while doxycycline and Bactrim (trimethoprim-sulfamethoxazole) are preferred when MRSA is suspected or confirmed. 1
Coverage Spectrum by Antibiotic
Cephalexin (First-Generation Cephalosporin)
Primary Coverage:
- Excellent activity against β-hemolytic streptococci (Group A Streptococcus pyogenes), which are the predominant pathogens in non-purulent cellulitis 1
- Excellent activity against methicillin-susceptible S. aureus (MSSA) 1
- Stable against gastric acid degradation with uniform absorption, ensuring reliable bioavailability 2, 3
Limited/No Coverage:
- No clinically relevant activity against MRSA 1, 4
- Poor activity against Haemophilus influenzae (50% failure rate in otitis media caused by this organism) 5
- No coverage for atypical organisms, gram-negative rods beyond basic urinary pathogens, or anaerobes 2
Doxycycline (Tetracycline)
Primary Coverage:
- Effective against MRSA - recommended as first-line oral therapy for MRSA skin infections 1
- Good activity against Aeromonas hydrophila and Vibrio vulnificus (when combined with other agents) 1
- Excellent activity against Pasteurella multocida (animal bites) 1
- Good activity against Eikenella corrodens (human bites), staphylococci, and anaerobes 1
Limited/No Coverage:
- Uncertain activity against β-hemolytic streptococci - the Infectious Diseases Society of America notes that activity against these organisms is "not known" 1
- Some streptococci are resistant to tetracyclines 1
- Should be combined with a β-lactam (like cephalexin or amoxicillin) when dual coverage for streptococci and MRSA is needed 1
Bactrim/TMP-SMX (Trimethoprim-Sulfamethoxazole)
Primary Coverage:
- Effective against MRSA - recommended as first-line oral therapy for MRSA skin infections 1
- Good activity against aerobic gram-positive and gram-negative organisms 1
- Bactericidal (unlike doxycycline which is bacteriostatic) 1
Limited/No Coverage:
- Uncertain activity against β-hemolytic streptococci - similar to doxycycline, the IDSA states activity is "not known" 1
- Poor activity against anaerobes 1
- Should be combined with a β-lactam (like cephalexin or amoxicillin) when dual coverage for streptococci and MRSA is needed 1
Clinical Application Algorithm
For Non-Purulent Cellulitis (No Abscess/Drainage)
Use cephalexin monotherapy (500 mg QID for 5-7 days) 1
- MRSA is an uncommon cause of typical cellulitis (96% success rate with β-lactams alone in high-MRSA prevalence centers) 1
- A randomized trial demonstrated no additional benefit from adding TMP-SMX to cephalexin for pure cellulitis (cure rates 83.5% vs 85.5%, difference -2.0%, 95% CI -9.7% to 5.7%) 1, 4
For Purulent Skin Infections (Abscesses, Furuncles)
Consider MRSA coverage with doxycycline (100 mg BID) or TMP-SMX (1-2 double-strength tablets BID) 1
- These infections are most likely due to S. aureus, including MRSA 1
- Incision and drainage is the primary intervention; antibiotics are adjunctive 1
When Dual Coverage Needed (Streptococci + MRSA)
Combine either doxycycline OR TMP-SMX with cephalexin 1
- Indications include: penetrating trauma, IV drug use, purulent drainage with surrounding cellulitis, or documented MRSA infection elsewhere 1
- Do not use doxycycline or TMP-SMX alone for non-purulent infections without β-lactam coverage 1
Critical Caveats
Age Restrictions:
- Doxycycline is contraindicated in children <8 years due to tooth discoloration risk 1
- Fluoroquinolones are contraindicated in children <18 years 1
Clinical Failure Patterns:
- If a patient fails cephalexin monotherapy for cellulitis, consider adding MRSA coverage rather than switching entirely 1
- For infections with high clinical suspicion for MRSA (healthcare-associated, prior MRSA history, severe systemic toxicity), start with dual coverage from the outset 1
Resistance Considerations: