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.
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 a MIC(50) of 1 μg/ml and MIC(90) of 2 μg/ml for linezolid. For coagulase-negative staphylococci (n = 7), viridans group streptococci (n = 15), and beta-hemolytic streptococci (n = 3), the MICs ranged from 0.03 to 0.25 μg/ml for tedizolid and from 0.12 to 1 μg/ml for linezolid. The microbiological eradication rates at the test-of-cure visit (7 to 14 days posttreatment) 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. The 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 its 4-fold-greater potency in comparison with linezolid. All dosages of tedizolid phosphate showed excellent microbiological and clinical efficacy against MRSA and MSSA.
Trius Therapeutics, Inc., San Diego, California, USA.
Philippe
P
Prokocimer
Paul
P
Bien
Carisa
C
Deanda
Chris M
CM
Pillar
Ken
K
Bartizal
D000081:Acetamides / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010755:Organophosphates / Q000378:metabolism / Q000494:pharmacology*; D010080:Oxazoles / Q000378:metabolism / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects* / Q000254:growth & development; D013777:Tetrazoles / Q000494:pharmacology*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D003470:Culture Media; D010755:Organophosphates; D010080:Oxazoles; D023303:Oxazolidinones; D013777:Tetrazoles; C546016:tedizolid; D000069349:Linezolid; C515040:tedizolid phosphate