Tedizolid equivalent to linezolid for skin infections

Tedizolid equivalent to linezolid for skin infections
Tedizolid equivalent to linezolid for skin infections

HealthDay News -- Acute bacterial skin and soft tissue infections responded equally well to treatment with linezolid (Zyvox) or a short course of the investigational agent tedizolid, results of a randomized trial showed.

Treatment with 200 mg of tedizolid phosphate once daily for 6 days was statistically noninferior in efficacy to 600 mg of linezolid twice daily for 10 days at both early (at day 2 to 3) and late time points (at day 11) and was generally well tolerated.

About 80% of patients had early responses to both drugs and post-treatment success rates ranged from 85% to 86%, Philippe Prokocimer, MD, of Trius Therapeutics in San Diego, and colleagues reported in Journal of the American Medical Association.

"Tedizolid phosphate may be a reasonable alternative to linezolid for treating acute bacterial skin and soft tissue infections," they wrote.

Although ABSSIs generally respond well to available antibiotic therapies, use is limited due to concerns about antimicrobial resistance, and only one drug -- linezolid -- is currently approved for use against complicated SSSIs caused by methicillin-resistant Staphylococcus aureus (MRSA).

“Increasingly, ABSSSIs are associated with drug-resistant pathogens, and many antimicrobial agents have adverse effects restricting their use," the researchers wrote.

So Prokocimer and colleagues conducted a phase-3 noninferiority trial to assess the safety and efficacy of tedizolid phosphate -- a novel oxazolidinone prodrug that has demonstrated activity against all clinically relevant gram-positive pathogens -- in comparison to linezolid.

The multicenter trial involved 81 study centers and 667 adults aged 18 years or older, who had cellulitis/erysipelas, major cutaneous abscess, or wound infections surrounded by erythema and a minimum lesion surface area of 75 cm2.

Participants were randomly assigned to receive treatment with a once-daily dose of 200 mg oral tedizolid phosphate for six days (n=332) or 600 mg of oral linezolid every 12 hours for 10 days (n=335). Follow-up was performed 48 to 72 hours after the first dose of randomized therapy, at the end of treatment, and 7 to 14 days after the end of treatment. The primary endpoint was clinical response at the first assessment.

More than half of patients -- 68% -- had one or more pathogens isolated from the primary lesion, 99% of which were gram positive. S. aureus was the most common pathogen isolated from primary lesions, including MRSA in 178 patients, representing more than 40% of positive cultures.

Early clinical treatment response rates were 79.5% in the tedizolid phosphate group and 79.4%in the linezolid group. At the end of treatment (day 11), the sustained clinical treatment response rates were 69.3% and 71.9% percent, respectively. At a post-therapy evaluation visit one to two weeks after the end-of-treatment visit, the investigator-assessed clinical treatment success rates were 85.5 and 86%, respectively.

The tedizolid arm had an adverse event rate of 40.8% versus 43.3% in the linezolid arm, including thrombocytopenia rates of 2.3% and 4.9%, respectively.

In an accompanying editorial, Shira Doron, MD, and Helen W. Boucher, MD, of Tufts Medical Center in Boston, pointed out if tedizolid wins FDA approval, it would be the first oral drug in the Infectious Diseases Society of America initiative to bring 10 new antibiotics to market by 2020.

References

  1. Prokocimer P et al. JAMA. 2013; 309: 559-569.
  2. Doron S, Boucher HW. JAMA. 2013; 309: 609-611.
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