Affiliation:
1. Trius Therapeutics, Inc., San Diego, California, USA
2. Eurofins Medinet, Chantilly, Virginia, USA
Abstract
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 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
78 articles.
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