Cited by 101Antimicrobial Resistance in StaphylococcusAntibiotic Resistance in BacteriaAntibiotic Use and Resistance

Tedizolid for the Management of Human Infections: In Vitro Characteristics

Locke, Jeffrey B., Zurenko, Gary E., Shaw, Karen Joy, Bartizal, Kenneth·2014·Clinical Infectious Diseases

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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  • Carriage of cfr does not appear to confer resistance to the recently FDA-approved oxazolidinone tedizolid.

    “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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Authors
Locke, J. B., Zurenko, G. E., Shaw, K. J., & Bartizal, K.
Affiliations
Cubist Pharmaceuticals (United States) (US)
Venue
Clinical Infectious Diseases
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › 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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