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The oxazolidinones: past, present, and future
Karen Joy Shaw1, Michael R Barbachyn
1Trius Therapeutics, Inc., Department of Biology, San Diego, California 92121, USA. kshaw@triusrx.com
Annals of the New York Academy of Sciences
|December 24, 2011
Summary
New oxazolidinone antibiotics show promise for treating bacterial infections, with several in clinical trials. Challenges remain in overcoming resistance, particularly from the cfr gene.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Infectious Diseases
Background:
- The success of linezolid spurred the development of novel oxazolidinone antibiotics.
- Numerous oxazolidinones have entered clinical development, but many faced discontinuation due to suboptimal efficacy, pharmacokinetics, or safety concerns like myelosuppression.
Observation:
- Four oxazolidinones are currently in clinical evaluation for various infections.
- Tedizolid phosphate is the most advanced, in Phase 3 trials for skin infections.
- Radezolid, sutezolid, and AZD5847 are in earlier stages of clinical development for skin infections, pneumonia, and tuberculosis.
Findings:
- Oxazolidinones generally exhibit low resistance rates due to their mechanism targeting 23S ribosomal RNA.
- Maintaining potency against strains with the mobile cfr gene is a significant challenge for this class of antibiotics.
Implications:
- Continued research into oxazolidinones is crucial for addressing bacterial infections and combating antimicrobial resistance.
- Overcoming resistance mechanisms, such as those conferred by the cfr gene, is essential for the future clinical utility of oxazolidinones and other 50S ribosome inhibitors.
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