The questions I get asked most are, “How do you treat cellulitis? Do I need to cover methicillin-resistant Staphylococcus aureus (MRSA)?”

With the emergence of community-associated MRSA as the most common cause of purulent skin infections in the United States, treatment of cellulitis (without a wound or discharge) has veered toward combination cephalexin and trimethoprim/sulfamethoxazole (TMP/SMX), the latter antibiotic added to cover MRSA. Recently, my colleagues and I published the results of a placebo-controlled trial that demonstrated that TMP/SMX treatment of patients with a drained skin abscess (most caused by MRSA) was associated with better outcomes (eg, higher cure rates and lower rates of recurrences, additional drainage procedures, hospitalizations, and household infections). So it’s logical that MRSA coverage would lead to better outcomes for cellulitis.

Infectious Diseases Society of America (IDSA) treatment guidelines state that uncomplicated cellulitis can be treated with just penicillin, providing fodder for yet another target for ED antibiotic-overuse shaming. Get real; in practice, no one, not even an infectious disease specialist, uses penicillin alone to treat cellulitis, except maybe for redness around the rim of a syphilitic chancre!

Unlike with abscesses, we almost never know the cause of cellulitis because there’s nothing to culture. Studies have tried unsuccessfully to use conventional cultures of skin biopsies. You may recall being directed as an intern to aspirate the leading edge. All for naught. Serological studies have suggested -strep, but these tests might yield false positives. Rarely, a blood culture kicks out a strep or staph, but these cases hardly reflect usual circumstances. Our group even tried to unlock this mystery by comparing polymerase chain reaction and pyrosequencing results from skin biopsies of the infected and opposite limb uninfected site with no luck.¹

In the May 23, 2017, issue of JAMA, our five-ED research group reported on the first large trial to directly address whether the addition of an antibiotic with MRSA activity resulted in better outcomes among patients followed for four to six weeks. Five-hundred mostly adult patients with cellulitis were randomized to receive either oral cephalexin (500 mg QID) plus placebo or cephalexin (500 mg QID) plus TMP/SMX (2 DS BID) for seven days. This was “pure” cellulitis without a wound or drainage.

As you can see from Table 1, outcomes were similar between the groups in terms of initial cure rates, recurrent infections, and additional drainage procedures. Of interest was that among the minority who failed in each group, some developed abscesses or wounds that grew MRSA. This suggested that MRSA plays a role in some cellulitis cases, but overall, adding an antibiotic with MRSA activity did not improve outcomes.

Table 1: Effectiveness of Adding a MRSA-Targeting Antibiotic to Cellulitis Treatment

I am next most frequently asked, “Do you really work with Dr. Greg Moran?” Yes, so for this article, I interviewed Gregory J. Moran, MD, at the department of emergency medicine and division of infectious diseases at Olive View–UCLA Medical Center, David Geffen School of Medicine at UCLA in Los Angeles, who was the paper’s first author.

DT: Greg, is it true that after your landmark 2006 New England Journal of Medicine article describing the emergence of MRSA, people started calling you “Mr. SA”?³

GM: That’s one of the nicer things they call me. I prefer that to, “Yo, Pus-Dawg!”

DT: What made this new study so awesome that people will frequently quote you?

GM: There aren’t many studies of commonly used generic antibiotics because pharma only funds trials of newer and more expensive drugs, so props to the NIH. Unlike one previous similar trial by Dr. Dan Pallin, this study was large enough to answer the question with some confidence.⁴ Also, we defined specific failure criteria rather than leaving it to the clinician’s judgment and allowed up to a 25 percent increase in erythema size in the first 48 hours since many successfully treated patients may initially worsen before improving.

DT: How should this trial’s results affect ED practice?

GM: Cephalexin alone for cellulitis! No need to routinely add a second (MRSA) antibiotic. We hope that this study will lead to a reduction in unnecessary antibiotic use.

DT: Finally, what do you make of the MRSA cases among the failures? Are there any exceptions when you might cover for MRSA?

GM: This study does not exclude the possibility that there’s a minority of patients who could benefit from MRSA treatment. About 9 percent of all participants had treatment failure due to MRSA, but this occurred in the same proportion in each treatment group and thus was not prevented with TMP/SMX treatment. We suspect some participants had small abscesses, undetected by ultrasound, which required drainage. While I use cephalexin alone for most cellulitis, I add TMP/SMX for patients with any purulent drainage (excluded from this trial), a history of recurrent abscesses and what looks like folliculitis (commonly caused by MRSA), and patients who are very ill.

DT: Thanks, Pus-Dawg! That means one fewer antibiotic prescription to write and one fewer for my patient to take.

Dr. Talan is professor of medicine in residence (emeritus) at the David Geffen School of Medicine at UCLA, chairman emeritus of the department of emergency medicine, and faculty in the division of infectious diseases at Olive View–UCLA Medical Center in Los Angeles.

Illustration by Adam Talan, Dr. Talan’s son, who obtained his degree in illustration from Academy of Art University in San Francisco and currently works in Los Angeles. See more of his work and contact him at adamtalan.com.

References

1. Crisp JG, Takhar SS, Moran GJ, et al. Inability of polymerase chain reaction, pyrosequencing, and culture of infected and uninfected site skin biopsy specimens to identify the cause of cellulitis. Clin Infect Dis. 2015;61(11):1679-1687.
2. 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.
3. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355(7):666-674.
4. Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis. 2013;56(12):1754-1762.