A 57-year-old man presents with pain and swelling in his leg. He has had low-grade fevers. He has a history of type 2 diabetes. On exam, his right lower extremity is warm, erythematous, and swollen to the midcalf. There is no purulence, fluctuance, or weeping skin. Labs are: WBC, 12,000; Na, 134; K, 5.2; BUN, 20; creatinine, 1.4.
What therapy would you recommend?
A) Ciprofloxacin.
B) Cefazolin.
C) Vancomycin.
D) Trimethoprim-sulfamethoxazole.
Dr. Douglas S. Paauw
Myth: Cellulitis treatment should include MRSA coverage.
Cellulitis is almost always caused by group A streptococcus. There are exceptional circumstances where other organisms must be considered; but for the most part, those situations are rare. With the growing concern for community-associated methicillin-resistant Staphylococcus aureus infection (MRSA), more and more patients are receiving empiric coverage for MRSA for all skin infections. Is this coverage for MRSA in patients with cellulitis a new myth in evolution?
In a study by Dr. Arthur Jeng and colleagues, all patients admitted to one hospital over a 3-year period with diffuse cellulitis were studied (Medicine 2010;89:217-26). A total of 179 patients were enrolled in the study; all patients had serologic studies for exposure to streptococci and what antibiotics they received, and outcomes were recorded.
Almost all patients with positive antibodies to streptococci responded to beta-lactam antibiotics (97%). But 91% of the patients who did not develop streptococcal antibodies also responded to beta-lactam antibiotics, for an overall response rate of 95% for treatment with beta-lactam antibiotics.
The most recent clinical practice guidelines published by the Infectious Diseases Society of America recommend treatment for infection with beta-hemolytic streptococci for outpatients with nonpurulent cellulitis (Clin. Infect. Dis. 2011;52:285-92). The addition of vancomycin is reserved for patients with purulence/evidence of abscess or exudate.
How common is it to prescribe antibiotics that cover MRSA in patients with cellulitis?
In a 2013 study, 61% of patients treated for cellulitis received antibiotics that included community-acquired MRSA coverage (Am. J. Med. 2013;126:1099-106).
A recent study looked at whether additional community-associated MRSA coverage with trimethoprim-sulfamethoxazole in addition to beta-lactam therapy for cellulitis showed any benefit over therapy with only a beta-lactam (Clin. Infect. Dis. 2013;56:1754-62). The study was a randomized, double-blind, placebo-controlled trial. The experimental group received trimethoprim-sulfamethoxazole and cephalexin, while the control group received cephalexin plus placebo.
There was no difference in outcome between the two groups, with the conclusion that addition of trimethoprim-sulfamethoxazole to cephalexin did not lead to a better outcome than cephalexin alone in patients with nonpurulent cellulitis.
A study by Dr. Thana Khawcharoenporn and Dr. Alan Tice looked at whether cephalexin, trimethoprim-sulfamethoxazole, or clindamycin was superior for the treatment of outpatient cellulitis (Am. J. Med. 2010;123:942-50). They concluded that trimethoprim-sulfamethoxazole and clindamycin were better than cephalexin. However, more than 50% of patients in this study had abscesses or ulcers – clinical criteria that increase the possibility of MRSA.
The most commonly used oral antibiotic for the coverage of community-associated MRSA is trimethoprim-sulfamethoxazole. This increasing use of TMP-sulfa has its risks, especially in elderly populations (Ann. Emerg. Med. 2014; 63:783-4). Trimethoprim-sulfamethoxazole can cause serious skin reactions and hyperkalemia (especially in the elderly and those with renal impairment), and the drug has a marked drug interaction with warfarin, leading to high risk of excessive anticoagulation.
These risks of TMP-sulfa use make it extremely important to have clear and worthwhile indications for its use.
The best evidence right now is that for simple cellulitis (no purulence, abscess, or exudate), treatment with a beta-lactam antibiotic is the best option. There is no need to add MRSA coverage to beta-lactam therapy.
If there is no response to treatment, then broadening coverage to include MRSA would be appropriate.
Dr. 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. Contact Dr. Paauw at dpaauw@uw.edu.