Official Title: “Empiric Therapy With Trimethoprim-Sulfamethoxazole or Doxycycline for Outpatient Skin and Soft Tissue Infections in an Area of High MRSA Prevalence: A Prospective Randomized Trial”

Background: In many communities, skin and soft tissue infections (SSTI) with MRSA have become more prevalent than infections with β-lactam susceptible bacteria. This has necessitated altered empiric antimicrobial therapy of SSTI to cover MRSA.

Objective: To evaluate empiric therapy with trimethoprim-sulfamethoxazole or doxycycline for outpatient SSTI in an area of high MRSA prevalence.

Design: Randomized, prospective, open-label investigation. Setting: Emergency Department of Parkland Hospital in Dallas, Texas. Patients: Adults with SSTI. Intervention: Empiric oral therapy with trimethoprim-sulfamethoxazole (160 mg/800 mg, twice daily) or doxycycline (100 mg, twice daily).

Measurement: The primary endpoint was clinical failure defined as hospitalization or change in antibiotic therapy over the 10 to 14 days after initial emergency department evaluation.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

As MRSA in more likely to be isolated from a SSTI than is a β-lactam susceptible organism at Parkland Hospital in Dallas, Texas, we performed a randomized, prospective, open-label investigation in our emergency department to determine the efficacy of empiric therapy using off-patent oral antibiotics (trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily or doxycycline 100 mg twice daily for 7 days) for the outpatient treatment of SSTI abscesses, requiring wound packing after incision and drainage but not requiring hospitalization. Only SSTI requiring wound packing were enrolled to eliminate the inclusion of smaller SSTI not requiring wound packing.

This investigation was approved by The University of Texas Southwestern Medical Center Institutional Review Board and included adults (≥ 18 years old) who were willing and able to provide informed consent. Inclusion criteria included being able to return for follow-up at 2 to 5 days after enrollment and being accessible by telephone for follow-up assessment at 10 to 14 days and 28 to 35 days after enrollment. Exclusion criteria excluded patients with contraindications or history of hypersensitivity reaction to any of the study treatment regimens, an infected prosthesis or device, concomitant bacteremia or deep infections (e.g.

osteomyelitis, necrotizing fasciitis, endocarditis), diabetic foot infections, known immunodeficiency, pregnant or breastfeeding, requirement of additional antimicrobial agents, and those who did not obtain assigned antibiotics.

The primary endpoint of this study was clinical failure defined as subsequent hospital admission, administration of intravenous antibiotics, or change in oral antibiotics over a period of 10-14 days after initial emergency department presentation. Repeated outpatient incision and drainage of the SSTI at 2 to 5 days after enrollment was not considered a clinical failure, if antibiotics were not changed and intravenous antibiotics were not administered. The trial enrolled patients from October 2005 to May 2006. Method of randomization was by generation of random numbers using www.randomizer.org, and alternately assigning these to the two treatment groups, and then sorting the numbers consecutively to determine the sequence of assigning treatment group to consecutively recruited patients.

Statistical analysis was performed with SigmaStat 3.0 software (SPSS Inc., Chicago, Illinois). This investigation had no external funding.

Intervention(s) in this Clinical Trial

• Drug: trimethoprim-sulfamethoxazole or doxycycline

Primary Measures

• The primary endpoint was clinical failure defined as hospitalization or change in antibiotic therapy over the 10 to 14 days after initial emergency department evaluation.

Inclusion Criteria:

• Outpatient treatment of SSTI abscesses, requiring wound packing after incision and drainage but not requiring hospitalization.
• Adults (≥ 18 years old) who were willing and able to provide informed consent.
• Able to return for follow-up at 2 to 5 days after enrollment and being accessible by telephone for follow-up assessment at 10 to 14 days and 28 to 35 days after enrollment.

Exclusion Criteria:

• Exclusion criteria excluded patients with contraindications or history of hypersensitivity reaction to any of the study treatment regimens, an infected prosthesis or device, concomitant bacteremia or deep infections (e.g. osteomyelitis, necrotizing fasciitis, endocarditis), diabetic foot infections, known immunodeficiency, pregnant or breastfeeding, requirement of additional antimicrobial agents, and those who did not obtain assigned antibiotics.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Texas Southwestern Medical Center

Overall Clinical Trial Officials and Contacts

Robert D Hardy, MD Study Director University of Texas Southwestern Medical Center  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00428818

Study ID Number: 072005-011

ClinicalTrials.gov Identifier: NCT00428818

Health Authority: United States: Institutional Review Board