Subgroup Analysis of Antibiotic Treatment for Skin Abscesses

Abstract

Study objective: Two large randomized trials recently demonstrated efficacy of methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotics for drained skin abscesses. We determine whether outcome advantages observed in one trial exist across lesion sizes and among subgroups with and without guideline-recommended antibiotic indications.

Methods: We conducted a planned subgroup analysis of a double-blind, randomized trial at 5 US emergency departments, demonstrating superiority of trimethoprim-sulfamethoxazole (320/1,600 mg twice daily for 7 days) compared with placebo for patients older than 12 years with a drained skin abscess. We determined between-group differences in rates of clinical (no new antibiotics) and composite cure (no new antibiotics or drainage) through 7 to 14 and 42 to 56 days after treatment among subgroups with and without abscess cavity or erythema diameter greater than or equal to 5 cm, history of MRSA, fever, diabetes, and comorbidities. We also evaluated treatment effect by lesion size and culture result.

Results: Among 1,057 mostly adult participants, median abscess cavity and erythema diameters were 2.5 cm (range 0.1 to 16.0 cm) and 6.5 cm (range 1.0 to 38.5), respectively; 44.3% grew MRSA. Overall, for trimethoprim-sulfamethoxazole and placebo groups, clinical cure rate at 7 to 14 days was 92.9% and 85.7%; composite cure rate at 7 to 14 days was 86.5% and 74.3%, and at 42 to 56 days, it was 82.4% and 70.2%. For all outcomes, across lesion sizes and among subgroups with and without guideline antibiotic criteria, trimethoprim-sulfamethoxazole was associated with improved outcomes. Treatment effect was greatest with history of MRSA infection, fever, and positive MRSA culture.

Conclusion: Treatment with trimethoprim-sulfamethoxazole was associated with improved outcomes regardless of lesion size or guideline antibiotic criteria.

Trial registration: ClinicalTrials.gov NCT00729937.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest:

Dr. Talan reports personal fees for consultation from Allergan, GlaxoSmithKline, and Paratek Pharmaceuticals and research grants from Allergan, Debiopharm, the Centers for Disease Control and Prevention, and the Patient Centered Outcomes Research Institute.

Dr. Moran reports personal fees for consultation and research grants from Allergan, and research grants from Allergan, Cempra, ContraFect, YES Biotechnology, the Centers for Disease Control and Prevention, and the Patient Centered Outcomes Research Institute.

Dr. Krishnadasan reports research grants from the Centers for Disease Control and Prevention, and the Patient Centered Outcomes Research Institute.

Dr. Lovecchio reports research grants from Allergan, NIH and the Centers for the Disease Control and Prevention.

Dr. Abrahamian reports personal fees from participation on speakers' bureaus for Merck, Allergan, and The Medicines Company, consultation for Cempra, Summit Therapeutics, Tetraphase Pharmaceuticals, Paratek Pharmaceuticals, and Janssen Research & Development, and research grants from the Centers for Disease Control and Prevention, Merck, and Cempra.

Dr. Karras has no potential conflicts of interest to report.

Dr. Steele reports research grants from Allergan and the Centers for the Disease Control and Prevention.

Dr. Rothman reports personal fees for consultation and research grant from Allergan, and research grants from Gilead (FOCUS Program) the Centers for the Disease Control and Prevention, NIH (NIAID), and HHS (BARDA). Dr. Rothman also participated in a 1 day consultation for Allergan with travel costs paid for by Allergan.

Dr. Mower reports research grants from Allergan, the Centers for Disease Control and Prevention, and the Patient Centered Outcomes Research Institute.

Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Enrollment, Randomization, and Follow-Up of Patients with a Drained Skin Abscess Treated with Trimethoprim-Sulfamethoxazole or Placebo.

Figure 2

Difference in Cure Rates* by Abscess Cavity Diameter† Among Participants with a Drained Skin Abscess Treated with Trimethoprim-Sulfamethoxazole Compared to Placebo. Overall, for trimethoprim-sulfamethoxazole and placebo groups, clinical cure rate at 7–14 days was 92.9% and 85.7% (difference, 7.2; 95% CI 3.2–11.2), composite cure rate at 7–14 was 86.5% and 74.3% (12.2; 95% CI 7.2–17.1) and extended composite cure at 42–56 days was 82.4% and 70.2% (difference, 12.2; 95% CI 6.8–17.6), respectively. * The between–group percentage point differences in cure rates were plotted by 1 cm increments of abscess cavity or erythema dimension. For each increment, cure rates were calculated for those that had the same or smaller size lesion. Outcomes were defined as follows: clinical cure was defined as resolution of all symptoms and signs of infection, or improvement such that no new antibiotics were prescribed (through 7–14 days after the end of treatment); composite cure was defined as resolution of all symptoms and signs of infection, or improvement such that no additional antibiotics and/or surgical drainage procedure were required (through 7–14 days and 42–56 days after the end of treatment). †Diameter was defined as the maximal linear dimension (length or width) of the abscess cavity, by probe after incision, and erythema, measured on the skin.

Figure 3

Difference in Cure Rates* by Erythema Diameter† Among Participants with a Drained Skin Abscess Treated with Trimethoprim-Sulfamethoxazole Compared to Placebo. Overall, for trimethoprim-sulfamethoxazole and placebo groups, clinical cure rate at 7–14 days was 92.9% and 85.7% (difference, 7.2; 95% CI 3.2–11.2), composite cure rate at 7–14 was 86.5% and 74.3% (12.2; 95% CI 7.2–17.1) and extended composite cure at 42–56 days was 82.4% and 70.2% (difference, 12.2; 95% CI 6.8–17.6), respectively. * The between-group percentage point differences in cure rates were plotted by 1 cm increments of abscess cavity or erythema dimension. For each increment, cure rates were calculated for those that had the same or smaller size lesion. Outcomes were defined as follows: clinical cure was defined as resolution of all symptoms and signs of infection, or improvement such that no new antibiotics were prescribed (through 7–14 days after the end of treatment); composite cure was defined as resolution of all symptoms and signs of infection, or improvement such that no additional antibiotics and/or surgical drainage procedure were required (through 7–14 days and 42–56 days after the end of treatment). †Diameter was defined as the maximal linear dimension (length or width) of the abscess cavity, by probe after incision, and erythema, measured on the skin.