SAN FRANCISCO A short course of therapy with torezolid phosphate cured virtually all patients with Staphylococcus aureusbased severe complicated skin and skin structure infections in a randomized, double-blind, phase II study.
A second-generation oxazolidinone related to linezolid, torezolid phosphate is a prodrug that can be given orally once per day, Dr. Philippe Prokocimer said in an interview. Dr. Prokocimer is medical director of Trius Therapeutics, the San Diegobased company that is developing the drug. He was one of the authors of the study, which was presented in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy, sponsored by the American Society for Microbiology.
The study involved 192 patients with S. aureus infections who were randomized to receive 200 mg, 300 mg, or 400 mg of torezolid phosphate once a day for 57 days. All patients had severe complicated skin and skin structure infections (cSSSI, also called acute bacterial skin structure infections), defined as skin infections that were 5 cm or greater in diameter and/or included systemic signs of infection. Patients with uncomplicated disease or with infections requiring gram-negative coverage were excluded, as were immunocompromised patients and those who had used antibiotics for more than 24 hours within 96 hours of the start of the study.
The clinical outcomes were similar in all dosage groups. Of the patients whose lesions were microbiologically evaluable, 96% achieved a clinical cure, including 95.7% of the patients with methicillin-susceptible S. aureus infections and 96.9% of the patients with methicillin-resistant S. aureus infections.
Five of the patients in the study experienced serious adverse events, but only one of these could have been drug relateda case of acute cholecystitis in an obese 57-year-old woman 2 days after the end of therapy. All other treatment-emergent adverse events were mild or moderate, with nausea the most common (19% of patients). The investigators saw no clinically significant changes in QTc.
"The side effect profile is stellar," Dr. Prokocimer said. "When we increase the dose, we don't see a dose-related increase in the incidence of side effects."
He noted that unlike linezolid, the 200-mg dose of torezolid phosphate had virtually no effects on patients' laboratory values and showed no evidence of immunosuppression. The 200-mg dose will be the subject of two pivotal phase III studies, due to begin in 2010.