February 27, 2013
Shorter Course Antibiotic Effective for Resistant Skin Infection
San Diego—Treatment with a newer antibiotic, tedizolid phosphate, once daily for 6 days was statistically as effective as the antibiotic linezolid twice daily for 10 days for acute bacterial skin infections, according to a recently published study.
The industry-sponsored study, which appeared in JAMA, said the clinical responses held up early in the infection, at Day 2 to 3, and over a sustained period, at Day 11, in potentially life-threatening acute bacterial skin and skin structure infections (ABSSSIs).
“Antimicrobials available for treatment of complicated skin and skin structure infections (SSSIs) are generally efficacious, but antimicrobial resistance and adverse effects limit their use. Linezolid, an oxazolidinone, is the only oral drug approved for complicated SSSI caused by methicillin-resistant Staphylococcus aureus (MRSA),” according to background information in the article.
Linezolid-resistant strains of MRSA have been reported, however. “Increasingly, ABSSSIs are associated with drug-resistant pathogens, and many antimicrobial agents have adverse effects restricting their use,” the authors note. “Tedizolid phosphate is a novel oxazolidinone in development for the treatment of ABSSSIs.”
In the study, researchers from Trius Therapeutics Inc. in San Diego sought to establish the noninferiority of tedizolid phosphate to linezolid in treating ABSSSIs. The phase III randomized trial, conducted from August 2010 through September 2011 at 81 study centers in North America, Latin America, and Europe, also monitored the comparative safety of the two drugs.
Researchers compared two groups of adults with ABSSSIs: 332 patients were treated with a 200-mg once-daily dose of oral tedizolid phosphate for 6 days, while 335 received 600 mg of oral linezolid every 12 hours for 10 days.
In the primary efficacy intent-to-treat (ITT) analysis—defined as no increase in lesion surface area from baseline and an oral temperature of 99.7°F or less—the response rates were 79.5% in the tedizolid phosphate group and 79.4% in the linezolid group. Sustained clinical treatment response rates at the end of treatment also were similar in the tedizolid phosphate and linezolid groups, 69.3% and 71.9%, respectively.
Related adverse events were mostly mild or moderate, occurring in 40.8% of patients in the tedizolid phosphate group and 43.3% of patients in the linezolid group.
“A short course of tedizolid phosphate was statistically noninferior to a 10-day course of linezolid for both early and sustained clinical responses in patients with ABSSSIs,” the authors conclude.
In an accompanying editorial, Shira Doron, MD, and Helen W. Boucher, MD, of Tufts Medical Center and Tufts University School of Medicine in Boston, suggested the results were promising but called for more studies.
“Tedizolid is a new oral antibiotic that appears efficacious using a short course and may have a better safety profile than linezolid,” according to the editorial writers. “The current study brings the Infectious Diseases Society of America’s 10X20 initiative one step closer to its goal of regulatory approval of 10 new antibacterial drugs with activity against drug-resistant bacteria by 2020. If approved, tedizolid will be the first oral drug in this initiative.”
“Future studies should add to the understanding of which patients may be treated safely with shorter-course therapy and further explore the correlation between early and sustained response in ABSSSI,” Doron and Boucher added.
|U.S. Pharmacist Social Connect