Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Treating Patients with Uncomplicated Cellulitis

JAMA; 2017 May 23/30; Moran, Krishnadasan, et al

The use of cephalexin plus trimethoprim-sulfamethoxazole compared to cephalexin alone among patients with uncomplicated cellulitis did not result in higher rates of clinical resolution of cellulitis, a recent study found. The multicenter, double-blind, randomized trial in 5 emergency departments included outpatients aged >12 years with cellulitis and no wound, purulent drainage, or abscess enrolled from April 2009 through June 2012. Final follow-up was August 2012. Patients received either cephalexin (500 mg, 4 times daily) plus trimethoprim-sulfamethoxazole (320 mg/1600 mg twice daily) for 7 days (n=248) or cephalexin plus placebo for 7 days (n=248). Researchers found:

  • In the per-protocol population, clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 165 (85.5%) of 193 in the cephalexin group.
  • In the modified intention-to-treat population, clinical cure occurred in 189 (76.2%) of 248 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 171 (69.0%) of 248 in the cephalexin group.
  • Adverse event rates and secondary outcomes through 7 to 9 weeks did not differ significantly.


Moran GJ, Krishnadasan A, Mower WR, et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs cephalexin alone on clinical cure of uncomplicated cellulitis. A randomized clinical trial. JAMA. 2017;317(20):2088-2096. doi:10.1001/jama.2017.5653.


Community-acquired MRSA has become an increasing concern over the last 10 years, leading many clinicians to treat cellulitis with trimethoprim-sulfamethoxazole with or without a cephalosporin in order to cover for MRSA. Coverage with trimethoprim-sulfamethoxazole may not be necessary, however, as most non-purulent skin infections are due to beta-hemolytic streptococci. MRSA usually causes purulent skin infections with the development of abscesses. In order to use the information from this study in clinical practice, it is important to recognize that all patients in the study had ultrasound exams to look for abscesses and were excluded from the trial if an abscess was present. What this means, for those of us who do not have ultrasound in our offices, is that if an abscess cannot be excluded clinically, it may make sense to cover for both strep and staph. Otherwise, this study strongly supports the current Infectious Disease Society of America’s (IDSA) recommendations for the treatment of skin infections:¹

Typical cases of cellulitis without systemic signs of infection should receive an antimicrobial agent that is active against streptococci. For cellulitis with systemic signs of infection (moderate nonpurulent), systemic antibiotics are indicated. Many clinicians could include coverage against methicillin-susceptible S. aureus (MSSA). For patients whose cellulitis is associated with penetrating trauma, evidence of MRSA infection elsewhere, nasal colonization with MRSA, injection drug use, or SIRS vancomycin or another antimicrobial effective against both MRSA and streptococci is recommended. —Neil Skolnik, MD

  1. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):147-159. doi:10.1093/cid/ciu296.