Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess

Abstract

Background: U.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear.

Methods: We conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period.

Results: The median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group.

Conclusions: In settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).

Figure 1. Enrollment, Randomization, and Follow-Up of Patients with a Drained Uncomplicated Cutaneous Abscess

Participants received a 7-day course of trial therapy; follow-up visits occurred on day 3 or 4 (during the treatment period), day 8 to 10 (end of the treatment period), day 14 to 21 (test-of-cure assessment), and day 49 to 63 (extended follow-up). The safety population included participants who received the study drug or placebo and did not return 100% of the doses at the end of the treatment period. The modified intention-to-treat 1 (mITT-1) population included participants who took at least one dose of active drug or placebo and had an in-person or telephone assessment through the test-of-cure visit, as well as those who withdrew from the trial, were lost to follow-up before final classification, or had missing or unassigned outcomes. The per-protocol population included participants who either took at least 75% of the doses provided during the first 5 days of the treatment period and had an in-person test-of-cure visit or were determined to have had clinical failure before the test-of-cure visit and took at least 75% of the doses provided during the first 48 hours of the treatment period. Participants who were excluded from the per-protocol population could have more than one reason for exclusion. The Food and Drug Administration guidance early end point (FDAGEEP) population included participants who took at least one dose of trial medication and completed the follow-up evaluation at 48 to 72 hours after the study drug or placebo was initiated. For information on the modified intention to treat 2 (mITT-2) population, see the Supplementary Appendix. TMP/SMX denotes trimethoprim–sulfamethoxazole.