Once daily treatment with a new antibiotic called tedizolid phosphate for six days proves just as successful as the antibiotic linezolid twice a day for ten 10 days, for patients with acute bacterial skin and skin structure infections.
According to the new study, published in JAMA:
“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 [a class of antibiotics], is the only oral drug approved for complicated SSSI caused by methicillin-resistant Staphylococcus aureus (MRSA).”
Acute bacterial skin and skin structure infections (ABSSSIs) can be dangerous and could necessitate surgery and hospitalization. ABSSIs are linked to drug-resistant pathogens, and antimicrobial agents generally have severe side effects, limiting their use.
Tedizolid phosphate is a new antibiotic that is being developed for the treatment of these infections.
Philippe Prokocimer, M.D., of Trius Therapeutics Inc., San Diego, and his fellow researchers executed a study that showed that tedizolid phosphate and linezolid have equal efficacy in treating ABSSSIs. The authors compared the safety of both drugs.
The phase 3, randomized trial took place from August 2010 through September 2011 throughout 81 centers in Latin America, North America, and Europe. The study was made up of 667 adults aged 18 or older, 332 of them were treated with tedizolid phosphate and 335 were treated with linezolid.
The participants given tedizolid phosphate were administered 200 mg once a day for six days, while those taking linezolid were administered 600 mg every 12 hours for 10 days.
In the first analysis of efficacy intent-to-treat (ITT), the response levels at the 48- to 72-hour examination were 79.5 percent of 332 patients in the tedizolid group and 79.4 percent of 335 patients in the linezolid group.
Sustained clinical treatment response levels following treatment were similar in both groups in the ITT analysis. Also similar in both groups, was the investigator-assessed clinical treatment response at the post-therapy evaluation (PTE).
The authors said, “Of particular interest are the similar treatment response rates in the tedizolid phosphate group (78.0 percent) and in the linezolid group (76.1 percent) in the sensitivity analysis that was based on the Foundation for the National Institutes of Health recommended outcome (≥ 20 percent decrease in lesion area).”
The clinical response rate at the PTE was high (85 percent) for 178 patients with MRSA, and similar in the linezolid and tedizolid phosphate groups.
Adverse effects that were mostly moderate occured in 40.8 percent of patients in the tedizolid group and 43.3 percent of patients in the linezolid group. Overall, the occurrence of adverse events was low.
The authors concluded :
“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. Results were consistent for primary and sensitivity analyses, using either objective criteria or investigators’ assessments, and treatment response rates were concordant for early and late time points.”
In an accompanying editorial, Shira Doron, M.D., and Helen W. Boucher, M.D., of Tufts Medical Center and Tufts University School of Medicine, Boston, make a few suggestions on the findings of this study:
“In the study by Prokocimer et al, only 2.4 percent of those who responded to treatment at the 48- to 72-hour assessment in the tedizolid group and 2 percent of those in the linezolid group experienced treatment failure at later time points, and only 7.2 percent and 8 percent, respectively, of the early nonresponders to treatment successfully responded to treatment at the later time point. This notable correlation between the early and late end points suggests that either is appropriate for noninferiority antibiotic trials. However, broad conclusions should not be drawn from this single study; future studies are needed to further enlighten the choice of end points.”
Written by Kelly Fitzgerald