Trius Therapeutics, Inc. (TSRX)

[DonShimoda]

This study confirms the potent in vitro activity of tedizolid against pathogenic gram-positive cocci, including MRSA, and 4-fold greater potency compared with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.

2012 Jun 11. [Epub ahead of print]
In Vitro Activity and Microbiological Efficacy of Tedizolid (TR-700) against Gram-Positive Clinical Isolates from a Phase 2 Study of Oral Tedizolid Phosphate (TR-701) in Patients with Complicated Skin and Skin Structure Infections.
Prokocimer PP, Bien P, Deanda C, Pillar CM, Bartizal K.
Source
Trius Therapeutics, Inc., San Diego, California.
Abstract
Tedizolid (TR-700, formerly torezolid) is the active moiety of the prodrug tedizolid phosphate (TR-701), a next-generation oxazolidinone, with high potency against gram-positive species, including methicillin-resistant Staphylococcus aureus (MRSA). A recently completed randomized, double-blind phase 2 trial evaluated 200, 300, or 400 mg of oral tedizolid phosphate once daily for 5 to 7 days in patients with complicated skin and skin structure infections. This report examines the in vitro activity of tedizolid and Zyvox® (linezolid) against gram-positive pathogens isolated at baseline and describes the microbiological and clinical efficacy of tedizolid. Of 196 isolates tested, 81.6% were S. aureus, and of these, 76% were MRSA. The MIC(50) and MIC(90) of tedizolid against both methicillin-susceptible S. aureus (MSSA) and MRSA were 0.25 µg/ml, compared with MIC(50) of 1 µg/ml and MIC(90) of 2 µg/ml with linezolid. For coagulase-negative staphylococci (n=7), viridans group streptococci (n=15), and ß-hemolytic streptococci (n=3), MICs ranged from 0.03-0.25 µg/ml for tedizolid and 0.12-1 µg/ml for linezolid. Microbiological eradication rates at the test-of-cure visit (7-14 days post-treatment) in the microbiologically evaluable population (n=133) were similar in all treatment groups, with overall eradication rates of 97.7% for all pathogens, 97.9% for MRSA, and 95.7% for MSSA. Clinical cure rates for MRSA and MSSA infections were 96.9% and 95.7%, respectively, across all dose groups. This study confirms the potent in vitro activity of tedizolid against pathogenic gram-positive cocci, including MRSA, and 4-fold greater potency compared with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.
PMID: 22687509 [PubMed - as supplied by publisher]