By Richard R. Watkins, MD, MS, FACP
Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
Dr. Watkins reports that he receives research support from Actavis.
SYNOPSIS: A multicenter, double-blind, randomized, clinical trial found that a seven-day course of trimethoprim-sulfamethoxazole following incision and drainage (I&D) resulted in a higher rate of cure for skin abscesses compared to I&D and placebo.
SOURCE: Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med 2016;374:823-832.
A skin abscess is a common presenting complaint in EDs, especially since the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) is the primary treatment, and antibiotics have been considered adjunctive. Talan et al aimed to clarify the role for trimethoprim-sulfamethoxazole (TMP-SMX) in treating skin abscesses after I&D and determine if this drug leads to a higher rate of cure.
This double-blind, randomized, clinical trial compared a seven-day outpatient course of TMP-SMX (320 mg/1,600 mg) twice a day to placebo in patients with cutaneous abscesses who received I&D in the ED. Patients older than 12 years of age were enrolled from five EDs between April 2009 and April 2013. They all presented with a skin abscess that existed for less than a week and measured at least 2 cm in diameter. The primary outcome was clinical cure of the abscess, which was determined seven to 14 days after the end of the treatment period.
Researchers randomized 630 patients to receive TMP-SMX, while 617 received placebo. Their median age was 35 years (range, 14-73 years) and 58.2% were male. MRSA grew in 45.3% of the wound cultures, and 97.4% of the strains were susceptible to TMP-SMX. The abscess cure rate was 80.5% in the TMP-SMX group compared to 73.6% in the placebo group (P = 0.005) in the modified intention-to-treat population, which included all participants who took at least one dose of TMP-SMX or placebo. In the per-protocol group, which included patients who took ≥ 75% of the total doses of study drug during the first five days and experienced a test-of-cure visit, clinical cure for those who received TMP-SMX was 92.9% vs. 85.7% for placebo (P < 0.001). TMP-SMX was superior to placebo for most of the secondary outcomes, including lower rates of subsequent surgical drainage procedures, skin infections at a new site, and infections among household members. Gastrointestinal symptoms were the most common adverse events, which occurred among 42.7% in the TMP-SMX group and 36.1% in the placebo group.
COMMENTARY
The decision to prescribe oral antibiotics for uncomplicated skin abscesses after I&D has been controversial. The potential benefits, including faster healing, reduced future occurrences, and decreased transmission to household contacts, must be weighed against the risks of side effects, potentially spreading antibiotic resistance, Clostridium difficile infection, and the cost of medication. The 2014 Infectious Diseases Society of America guidelines recommend antibiotics after I&D for patients with impaired host defenses or evidence of systemic inflammatory response syndrome, including temperature > 38°C or < 36°C, tachypnea > 24 breaths per minute, tachycardia > 90 beats per minute, or white blood cell count > 12,000 or < 4,000 cells/µL, which is based on moderate-quality evidence.1 Of the five studies cited for this recommendation, only two were conducted during the current MRSA era: one included children and one included adults. The latter was a multicenter, double-blind, randomized, placebo-controlled trial that found treatment with TMP-SMX after I&D did not reduce treatment failure but did decrease the formation of subsequent lesions.2 However, this study and others have been criticized for being underpowered because the cure rate with I&D alone exceeds 80% and large sample sizes are necessary to test for small differences in cure rates.
The Talan et al study provides some welcome clarity to the role for antibiotics after I&D. Their study was large, well-designed, and found a significant benefit for a seven-day course of TMP-SMX. The low rate of adverse events with TMP-SMX was surprising, since this drug is one of the most frequent antibiotics to cause adverse reactions, including ones that lead to ED visits.3 Although the risks associated with antibiotics are well known, one also must appreciate that higher cures of primary abscesses will subsequently lead to reduced costs from fewer follow-up visits, surgeries, hospitalizations, and less spreading of infection to others in households and communities. Although it is the latest, the Talan et al study will likely not be the last on the topic. Clinicians must manage cutaneous abscesses based on careful interpretation of the available data. Therefore, after a frank discussion with the patient about the risks and benefits, a seven-day course of an antibiotic with MRSA activity (e.g., TMP-SMX or doxycycline) should be prescribed after I&D of a moderate-sized (≥ 2 cm) cutaneous abscess.
REFERENCES
- 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:e10-52.
- Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med 2010;56:283-287.
- Shehab N, Patel PR, Srinivasan A, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis 2008;47:735-743.