Affiliation:
1. Dong-A Pharmaceutical Co., Yongin-Si, South Korea
2. Trius Therapeutics, Inc., San Diego, California, USA
Abstract
ABSTRACT
The
in vitro
activity of tedizolid (previously known as torezolid, TR-700) against penicillin-resistant
Streptococcus pneumoniae
(PRSP) clinical isolates and the
in vivo
efficacy of tedizolid phosphate (torezolid phosphate, TR-701) in murine models of PRSP systemic infection and penicillin-susceptible
S. pneumoniae
(PSSP) pneumonia were examined using linezolid as a comparator. The MIC
90
against 28 PRSP isolates was 0.25 μg/ml for tedizolid, whereas it was 1 μg/ml for linezolid. In mice infected systemically with a lethal inoculum of PRSP 1 h prior to a single administration of either antimicrobial, oral tedizolid phosphate was equipotent to linezolid (1 isolate) to 2-fold more potent than linezolid (3 isolates) for survival at day 7, with tedizolid phosphate 50% effective dose (ED
50
) values ranging from 3.19 to 11.53 mg/kg of body weight/day. In the PSSP pneumonia model, the ED
50
for survival at day 15 was 2.80 mg/kg/day for oral tedizolid phosphate, whereas it was 8.09 mg/kg/day for oral linezolid following 48 h of treatment with either agent. At equivalent doses (10 mg/kg once daily tedizolid phosphate or 5 mg/kg twice daily linezolid), pneumococcal titers in the lungs at 52 h postinfection were approximately 3 orders of magnitude lower with tedizolid phosphate treatment than with linezolid treatment or no treatment. Lung histopathology showed less inflammatory cell invasion into alveolar spaces in mice treated with tedizolid phosphate than in untreated or linezolid-treated mice. These results demonstrate that tedizolid phosphate is effective in murine models of PRSP systemic infection and PSSP pneumonia.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference19 articles.
1. In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)
2. Comparative
In Vitro
Antimicrobial Activities of Torezolid (TR-700), the Active Moiety of a New Oxazolidinone, Torezolid Phosphate (TR-701), Determination of Tentative Disk Diffusion Interpretive Criteria, and Quality Control Ranges
3. Drug‐ResistantStreptococcus pneumoniae
4. Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae-–United States, 2006-2007;Centers for Disease Control and Prevention;MMWR Morb. Mortal. Wkly. Rep.,2008
5. Clinical and Laboratory Standards Institute. 2008. Performance standards for antimicrobial susceptibility testing; 18th informational supplement. M100-S18. Clinical and Laboratory Standards Institute Wayne PA.
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献