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Tedizolid for the Management of Human Infections: In Vitro Characteristics
Abstract
The emerging antibiotic resistance of Gram-positive pathogens represents a significant challenge to the management of human infections. The novel oxazolidinone tedizolid demonstrates antimicrobial activity across a broad range of Gram-positive pathogens and greater potency than linezolid against wild-type and drug-resistant pathogens, including linezolid-resistant Staphylococcus aureus strains possessing mutations in chromosomal genes encoding 23S rRNA or ribosomal proteins L3 or L4. Strains harboring such mutations are also selected for much less frequently with tedizolid than with linezolid. In addition, tedizolid has a significant potency advantage over linezolid-resistant strains carrying the horizontally transferable cfr gene. Methylation of A2503 of 23S rRNA by the Cfr methyltransferase confers resistance to linezolid (and a variety of other 50S ribosomal subunit-targeted antibiotics) but not to tedizolid because of structural differences in A-ring C5 substituents between the 2 drugs. The greater potency and improved resistance profile of tedizolid provides the microbiologic basis for considering this molecule as an alternative to linezolid for the treatment of serious infections caused by Gram-positive pathogens.
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“Importantly, carriage of cfr does not appear to confer resistance to the recently FDA-approved oxazolidinone tedizolid (67).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [67]
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“13,14 In addition to the retained in vitro activity against linezolid-resistant cfr-carrying isolates, previous studies showed that tedizolid is well tolerated and has a lower propensity for neuropathies than its in-class comparator linezolid.”
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“The tedizolid in vitro activity tested against key ABSSSI pathogens, such as Staphylococcus aureus (MIC90, 0.5 g/ml) and beta-hemolytic streptococci (MIC90, 0.25 g/ml) (5–7), demonstrated a potency that is at least 4-fold greater than that of the other currently marketed oxazolidinone, linezolid (8).”
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Metadata
- Authors
- Locke, J. B., Zurenko, G. E., Shaw, K. J., & Bartizal, K.
- Affiliations
- Cubist Pharmaceuticals (United States) (US)
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01-01
- Volume
- 58
- Issue
- suppl_1
- Pages
- S35-S42
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W2017411933
- Cited by
- 101
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 3 · 2019: 10 · 2018: 9 · 2017: 13 · 2016: 22 · 2015: 13 · 2014: 8
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Infectious Diseases › Antibiotic Use and Resistance
- Keywords
- tedizolid, oxazolidinones, linezolid resistance, Gram-positive bacterial infections, Staphylococcus aureus, 23S rRNA mutations, cfr gene, antimicrobial susceptibility, in vitro antimicrobial activity
- MeSH terms
- Linezolid, Acetamides, Ribosomal Protein L3, Anti-Bacterial Agents, Humans, Oxazoles, Organophosphates, Ribosomal Proteins, RNA, Ribosomal, 23S, tRNA Methyltransferases, Staphylococcal Infections, Staphylococcus aureus, Point Mutation, Gene Transfer, Horizontal, Oxazolidinones, Drug Resistance, Bacterial
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