The Biggest Myth in Cellulitis Treatment

Douglas S. Paauw, MD

March 11, 2021

An obese 64-year-old man with type 2 diabetes presents with redness and warmth of his lower left leg.

He noticed discomfort today and saw that his left lower leg had redness and was warm. He does not recall scratches or injury to his leg. He has not had fever or chills. He has no other symptoms. His diabetes has been well controlled with diet and metformin.

On exam, his blood pressure is 120/70, pulse is 80, temperature is 37 degrees Celsius.

In the left lower extremity, the patient had 1+ edema at the ankle, with a 14-cm x 20-cm warm, erythematous area just above the ankle and extending proximally.

His labs found an HCT of 44 and a WBC of 12,000. What do you recommend?

A. Vascular duplex exam

B. 1st generation cephalosporin

C. 1st generation cephalosporin + TMP/Sulfa

D. Oral clindamycin

E. IV vancomycin

This patient has cellulitis and should receive a beta lactam antibiotic, which will have the best coverage and lowest minimal inhibitory concentration for the likely organism, beta hemolytic streptococci. Clindamycin would likely work, but it has greater side effects. This patient does not need coverage for methicillin-resistant staphylococcus aureus (MRSA). I know many of you, if not most, know this, but I want to go through relevant data and formal recommendations, because of a recent call I received from a patient.

My patient had a full body rash after receiving cephalexin + TMP/sulfa [trimethoprim-sulfamethoxazole] treatment for cellulitis. In recent years the addition of TMP/sulfa to strep treatment to also cover MRSA has become popular, especially in emergency department and urgent care settings.

Moran and colleagues studied cephalexin + TMP/sulfa vs. cephalexin and placebo in patients with uncomplicated cellulitis.1 The outcome measured was clinical cure, and there was no difference between groups; clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus TMP/sulfa group vs. 165 (85.5%) of 193 in the cephalexin group (difference, −2.0%; 95% confidence interval, −9.7% to 5.7%; P = .50).

Jeng and colleagues studied patients admitted for a cellulitis, and evaluated the patients’ response to beta-lactam antibiotics.2 Patients had acute and convalescent serologies for beta hemolytic strep. Almost all evaluable patients with positive strep studies (97%) responded to beta-lactams, and 21 of 23 (91%) with negative studies responded to beta-lactams (overall response rate 95%). This study was done during a time of high MRSA prevalence.

The most recent Infectious Diseases Society of America guidelines for skin and soft tissue infections, recommend oral penicillin, cephalexin, dicloxacillin, or clindamycin for mild cellulitis, and IV equivalent if patients have moderate cellulitis.3 If abscesses are present, then drainage is recommended and MRSA coverage. Kamath and colleagues reported on how closely guidelines for skin and soft tissue infections were followed.4 In patients with mild cellulitis, only 36% received guideline-suggested antibiotics. The most common antibiotic prescribed that was outside the guidelines was trimethoprim-sulfamethoxazole.

Myth: Cellulitis treatment should include MRSA coverage.

My advice: Stick with beta-lactam antibiotics, unless an abscess is present. There is no need to add MRSA coverage for initial treatment of mild to moderate cellulitis.

Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Paauw has no conflicts to disclose. Contact him at


1. Moran GJ et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs. cephalexin alone on clinical cure of uncomplicated cellulitis: A randomized clinical trial. JAMA 2017 May 23;317(20):2088-96.

2. Jeng Arthur et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis. Medicine. 2010;July;89(4):217-26.

3. Stevens DL 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):e10-e52.

4. Kamath RS et al. Guidelines vs. actual management of skin and soft tissue infections in the emergency department. Open Forum Infect Dis. 2018 Jan 12;5(1):ofx188.

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