Strategies Using Off-Patent Antibiotics for Methicillin Resistant S. Aureus "STOP MRSA"

Summary

The purpose of this study is to determine the optimal outpatient treatment strategy of uncomplicated skin and soft tissue infection (SSTI) in areas of the United States where the prevalence of Community-Acquired Methicillin-Resistant Staphylococcus (S.) aureus (CA-MRSA) is high. Infection with the S. aureus bacteria that is resistant to antibiotics is a cause of SSTIs. Three oral antibiotics will be tested for off patent treatment. Patients will receive Trimethoprim/Sulfamethoxazole (TMP/SMX), placebo (substance containing no medication), clindamycin, or cephalexin or some combination of these. The study population will include 2,235 volunteers, children 13 years of age and over and adults presenting to 5 large urban Emergency Departments. Therapy for acute uncomplicated SSTIs, including abscess, infected wound, and cellulitis will start on the day of enrollment. Participants may be involved in study related procedures for about 9 weeks.

Timeline

Start

2009-04

Primary completion

2013-05

Completion

2013-06

Outcome

Mixed primary results

paper Trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. PMID 26962903 ↗

paper Among patients with uncomplicated cellulitis, the use of cephalexin plus trimethoprim-sulfamethoxazole compared to cephalexin alone did not result in higher rates of clinical resolution of cellulitis in the per-protocol analysis. PMID 28535235 ↗

paper In settings where MRSA is prevalent, clindamycin and TMP-SMX produce similar cure and adverse event rates among patients with an uncomplicated wound infection. PMID 27025829 ↗

Publications

• Mower WR, Crisp JG, Krishnadasan A, Moran GJ, Abrahamian FM, Lovecchio F, Karras DJ, Steele MT, Rothman RE, Talan DA. Effect of Initial Bedside Ultrasonography on Emergency Department Skin and Soft Tissue Infection Management. Ann Emerg Med. 2019 Sep;74(3):372-380. doi: 10.1016/j.annemergmed.2019.02.002. Epub 2019 Mar 27.
• Talan DA, Moran GJ, Krishnadasan A, Abrahamian FM, Lovecchio F, Karras DJ, Steele MT, Rothman RE, Mower WR. Subgroup Analysis of Antibiotic Treatment for Skin Abscesses. Ann Emerg Med. 2018 Jan;71(1):21-30. doi: 10.1016/j.annemergmed.2017.07.483. Epub 2017 Oct 5.
• Moran GJ, Krishnadasan A, Mower WR, Abrahamian FM, LoVecchio F, Steele MT, Rothman RE, Karras DJ, Hoagland R, Pettibone S, Talan DA. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653.
• Talan DA, Lovecchio F, Abrahamian FM, Karras DJ, Steele MT, Rothman RE, Krishnadasan A, Mower WR, Hoagland R, Moran GJ. A Randomized Trial of Clindamycin Versus Trimethoprim-sulfamethoxazole for Uncomplicated Wound Infection. Clin Infect Dis. 2016 Jun 15;62(12):1505-1513. doi: 10.1093/cid/ciw177. Epub 2016 Mar 29.
• Talan DA, Mower WR, Krishnadasan A, Abrahamian FM, Lovecchio F, Karras DJ, Steele MT, Rothman RE, Hoagland R, Moran GJ. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016 Mar 3;374(9):823-32. doi: 10.1056/NEJMoa1507476.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	CEPHALEXIN ANHYDROUS	Small molecule	500 mg	Oral
Subject	Clindamycin	Unknown	300 mg	Oral
Subject	trimethoprim-sulfamethoxazole	Unknown	320 mg	Oral
Subject	trimethoprim-sulfamethoxazole	Unknown	1600 mg	Oral

Indications