Cited by 224Antimicrobial Resistance in StaphylococcusAntibiotic Resistance in BacteriaAntibiotic Use and Resistance

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Linezolid update: Stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms

Mendes, Rodrigo E., Deshpande, Lalitagauri M., Jones, Ronald N.·2014·Drug Resistance Updates

DOI 10.1016/j.drup.2014.04.002

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Abstract

Linezolid, approved for clinical use since 2000, has become an important addition to the anti-Gram-positive infection armamentarium. This oxazolidinone drug has in vitro and in vivo activity against essentially all Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The in vitro activity of linezolid was well documented prior to its clinical application, and several ongoing surveillance studies demonstrated consistent and potent results during the subsequent years of clinical use. Emergence of resistance has been limited and associated with invasive procedures, deep organ involvement, presence of foreign material and mainly prolonged therapy. Non-susceptible organisms usually demonstrate alterations in the 23S rRNA target, which remain the main resistance mechanism observed in enterococci; although a few reports have described the detection of cfr-mediated resistance in Enterococcus faecalis. S. aureus isolates non-susceptible to linezolid remain rare in large surveillance studies. Most isolates harbour 23S rRNA mutations; however, cfr-carrying MRSA isolates have been observed in the United States and elsewhere. It is still uncertain whether the occurrences of such isolates are becoming more prevalent. Coagulase-negative isolates (CoNS) resistant to linezolid were uncommon following clinical approval. Surveillance data have indicated that CoNS isolates, mainly Staphylococcus epidermidis, currently account for the majority of Gram-positive organisms displaying elevated MIC results to linezolid. In addition, these isolates frequently demonstrate complex and numerous resistance mechanisms, such as alterations in the ribosomal proteins L3 and/or L4 and/or presence of cfr and/or modifications in 23S rRNA. The knowledge acquired during the past decades on this initially used oxazolidinone has been utilized for developing new candidate agents, such as tedizolid and radezolid, and as linezolid patents soon begin to expire, generic brands will certainly become available. These events will likely establish a new chapter for this successful class of antimicrobial agents.

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Authors: Mendes, R. E., Deshpande, L. M., & Jones, R. N.
Affiliations: JMI Laboratories (US)
Tufts University (US)
Corresponding author: Mendes, Rodrigo E.
ORCID: Mendes, Rodrigo E.
Deshpande, Lalitagauri M.
Jones, Ronald N.
Venue: Drug Resistance Updates
Publisher: Elsevier BV
Published: 2014-04
Volume: 17
Issue: 1-2
Pages: 1-12
ISSN: 1368-7646 (ISSN-L)
DOI: 10.1016/j.drup.2014.04.002
OpenAlex: W1977069647
Cited by: 221
References: 124
Citations by year: 2026: 7 · 2025: 9 · 2024: 13 · 2023: 12 · 2022: 18 · 2021: 20 · 2020: 21 · 2019: 25 · 2018: 25 · 2017: 23 · 2016: 23 · 2015: 19 · 2014: 6
FWCI: 3.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Drug Resistance Updates (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: linezolid, oxazolidinones, antimicrobial resistance, 23S rRNA mutations, cfr gene, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, coagulase-negative staphylococci, Staphylococcus epidermidis, antimicrobial resistance surveillance, tedizolid, Gram-positive bacterial infections
MeSH terms: Linezolid, Acetamides, Ribosomal Protein L3, Anti-Bacterial Agents, Bacterial Proteins, Gram-Positive Bacteria, Humans, Microbial Sensitivity Tests, Mutation, Ribosomal Proteins, RNA, Ribosomal, 23S, Tetrazoles, Gram-Positive Bacterial Infections, Drug Approval, Oxazolidinones, Drug Resistance, Bacterial

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Linezolid update: Stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms

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