Is Cephalexin Sufficient for Purulent Cellulitis?
No, cephalexin alone is not sufficient for purulent cellulitis—you must add MRSA-active coverage with either trimethoprim-sulfamethoxazole or doxycycline, or switch to clindamycin monotherapy. 1
Critical Distinction: Purulent vs. Nonpurulent Cellulitis
The presence of purulent drainage fundamentally changes antibiotic selection because it signals likely MRSA involvement:
- For typical nonpurulent cellulitis, beta-lactam monotherapy (cephalexin alone) is the standard of care with 96% success rates 1
- For purulent cellulitis, empirical MRSA coverage is mandatory because community-associated MRSA is the predominant pathogen in purulent skin infections 2, 3
Evidence Against Cephalexin Monotherapy for Purulent Disease
The landmark 2017 JAMA trial and 2013 Clinical Infectious Diseases study both demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provides no benefit for pure cellulitis without purulent drainage 2, 4. However, these trials specifically excluded patients with purulent drainage, abscess, or wound infections—meaning their findings do not apply to your purulent cellulitis scenario 2, 4.
The FDA label for cephalexin lists skin and skin structure infections caused by S. aureus as an indication, but this predates the MRSA era and does not account for methicillin resistance 5.
Recommended Treatment Regimens for Purulent Cellulitis
First-line combination therapy options:
- Cephalexin 500 mg four times daily PLUS trimethoprim-sulfamethoxazole 320/1600 mg twice daily for 5 days 1
- Cephalexin 500 mg four times daily PLUS doxycycline 100 mg twice daily for 5 days 1
Alternative monotherapy (covers both streptococci and MRSA):
- Clindamycin 300-450 mg four times daily for 5 days (only if local MRSA clindamycin resistance <10%) 1, 6
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe 1. This applies to both combination therapy and clindamycin monotherapy 1.
Why Combination Therapy is Necessary
Purulent cellulitis requires coverage for both:
- Beta-hemolytic streptococci (covered by cephalexin) 1
- MRSA (NOT covered by cephalexin, requiring trimethoprim-sulfamethoxazole, doxycycline, or clindamycin) 1
Neither trimethoprim-sulfamethoxazole nor doxycycline provides reliable streptococcal coverage, which is why they must be combined with a beta-lactam when treating purulent cellulitis 1. Clindamycin uniquely covers both pathogens, avoiding the need for true combination therapy 1.
Common Pitfall to Avoid
Do not use cephalexin alone for purulent cellulitis simply because it worked for nonpurulent cases. The microbiology is fundamentally different—purulent drainage indicates MRSA until proven otherwise, and cephalexin lacks clinically relevant anti-MRSA activity despite in vitro susceptibility testing that may suggest otherwise 7.