Tedizolid for the Management of Human Infections: In Vitro Characteristics

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 wil...

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Bibliographic Details
Published in:Clinical infectious diseases 2014-01, Vol.58 (suppl_1), p.S35-S42
Main Authors: Locke, Jeffrey B., Zurenko, Gary E., Shaw, Karen Joy, Bartizal, Kenneth
Format: Article
Language:English
Subjects:
Acetamides - pharmacology
Acetamides - therapeutic use
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antimicrobials
Drug resistance
Drug Resistance, Bacterial
Drugs
Gene Transfer, Horizontal
Genes
Genetic mutation
Humans
Infections
Labor standards
Linezolid
Methicillin resistant staphylococcus aureus
Microbial sensitivity tests
Organophosphates - pharmacology
Organophosphates - therapeutic use
Oxazoles - pharmacology
Oxazoles - therapeutic use
Oxazolidinones
Oxazolidinones - pharmacology
Oxazolidinones - therapeutic use
Point Mutation
Quality assurance
Ribosomal Proteins - genetics
RNA, Ribosomal, 23S - genetics
RNA, Ribosomal, 23S - metabolism
Staphylococcal Infections - drug therapy
Staphylococcal Infections - microbiology
Staphylococcus
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - genetics
Staphylococcus infections
tRNA Methyltransferases - metabolism
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Summary: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.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cit616