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oxazolidinones

  • A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges
    Clinical Therapeutics
    A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges

    Ventriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically...

    Nilesh Kumta, Jason A. Roberts, Jeffrey Lipman, Wai Tat Wong, Gavin M. Joynt, Menino Osbert Cotta
  • Transferable Resistance Gene <em>optrA</em> in <span class="named-content genus-species" id="named-content-1">Enterococcus faecalis</span> from Swine in Brazil
    Mechanisms of Resistance
    Transferable Resistance Gene optrA in Enterococcus faecalis from Swine in Brazil

    OptrA is an ATP-binding cassette (ABC)-F protein that confers resistance to oxazolidinones and phenicols and can be either plasmid-encoded or chromosomally encoded. Here, we isolated 13 Enterococcus faecalis strains possessing a linezolid MIC of ≥4 mg/liter from nursery pigs in swine herds located across Brazil. Genome sequence comparison showed that these strains...

    Lara M. Almeida, François Lebreton, Anthony Gaca, Paulo M. Bispo, Jose T. Saavedra, Rodrigo N. Calumby, Luciano M. Grillo, Ticiano G. Nascimento, Pedro H. Filsner, Andrea M. Moreno, Michael S. Gilmore
  • Accumulation of Major Linezolid Metabolites in Patients with Renal Impairment
    Pharmacology
    Accumulation of Major Linezolid Metabolites in Patients with Renal Impairment

    In patients with renal impairment (n = 22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r2 = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential...

    Ernane Souza, Ryan L. Crass, Jeremy Felton, Kengo Hanaya, Manjunath P. Pai
  • Efflux-Mediated Resistance to New Oxazolidinones and Pleuromutilin Derivatives in <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> with Class Specificities in the Resistance-Nodulation-Cell Division-Type Drug Transport Pathways
    Mechanisms of Resistance
    Efflux-Mediated Resistance to New Oxazolidinones and Pleuromutilin Derivatives in Escherichia coli with Class Specificities in the Resistance-Nodulation-Cell Division-Type Drug Transport Pathways

    A major contribution of the resistance-nodulation-cell division (RND)-transporter AcrB to resistance to oxazolidinones and pleuromutilin derivatives in Escherichia coli was confirmed. However, we discovered significant differences in efflux inhibitor activities, specificities of the homologous pump YhiV (MdtF), and the impact of AcrB pathway mutations.

    ...
    Sabine Schuster, Martina Vavra, Winfried V. Kern
  • Tn<em>6674</em> Is a Novel Enterococcal <em>optrA</em>-Carrying Multiresistance Transposon of the Tn<em>554</em> Family
    Mechanisms of Resistance
    Tn6674 Is a Novel Enterococcal optrA-Carrying Multiresistance Transposon of the Tn554 Family

    The novel 12,932-bp nonconjugative multiresistance transposon Tn6674 was identified in the chromosomal DNA of a porcine Enterococcus faecalis strain. Tn6674 belongs to the Tn554 family of transposons. It shares the same arrangement of the transposase genes tnpA, tnpB, and tnpC with Tn554. However, in...

    Dexi Li, Xing-Yun Li, Stefan Schwarz, Mengyan Yang, Su-Mei Zhang, Wenbo Hao, Xiang-Dang Du
  • Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety
    Pharmacology
    Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety

    Linezolid is administered as a fixed dose to all patients despite evidence of increased exposure and myelosuppression in renal impairment. The objectives of these studies were to assess the risk of thrombocytopenia with standard-dose linezolid in renal impairment and to identify an alternate dosing strategy.

    Ryan L. Crass, Pier Giorgio Cojutti, Manjunath P. Pai, Federico Pea
  • Oxazolidinones Can Replace Clarithromycin in Combination with Rifampin in a Mouse Model of Buruli Ulcer
    Experimental Therapeutics
    Oxazolidinones Can Replace Clarithromycin in Combination with Rifampin in a Mouse Model of Buruli Ulcer

    Rifampin (RIF) plus clarithromycin (CLR) for 8 weeks is now the standard of care for Buruli ulcer (BU) treatment, but CLR may not be an ideal companion for rifamycins due to bidirectional drug-drug interactions. The oxazolidinone linezolid (LZD) was previously shown to be active against Mycobacterium ulcerans infection in mice but has dose- and duration-dependent...

    Deepak V. Almeida, Till F. Omansen, Si-Yang Li, Jin Lee, Jacques H. Grosset, Paul J. Converse, Eric L. Nuermberger
  • Myelosuppression with Oxazolidinones: Are There Differences?
    Letter to the Editor
    Myelosuppression with Oxazolidinones: Are There Differences?
    Cathy Hardalo, Thomas P. Lodise, Carisa De Anda
  • Use of Translational Pharmacokinetic/Pharmacodynamic Infection Models To Understand the Impact of Neutropenia on the Efficacy of Tedizolid Phosphate
    Pharmacology
    Use of Translational Pharmacokinetic/Pharmacodynamic Infection Models To Understand the Impact of Neutropenia on the Efficacy of Tedizolid Phosphate

    Tedizolid phosphate, the prodrug of the active antibiotic tedizolid, is an oxazolidinone for the treatment of acute bacterial skin and skin structure infections. Studies in a mouse thigh infection model demonstrated that tedizolid has improved potency and pharmacokinetics/pharmacodynamics (PK/PD) compared with those of linezolid.

    Jianying Xiao, Charles Gill, Lianzhu Liang, Jenny Liu, Jin Wu, Hwa-Ping Feng, Shawn Flanagan, Christopher Tan, Amy Flattery
  • Emergence and Within-Host Genetic Evolution of Methicillin-Resistant <em>Staphylococcus aureus</em> Resistant to Linezolid in a Cystic Fibrosis Patient
    Mechanisms of Resistance
    Emergence and Within-Host Genetic Evolution of Methicillin-Resistant Staphylococcus aureus Resistant to Linezolid in a Cystic Fibrosis Patient

    Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the antistaphylococcal antibiotics widely used in this context.

    Caroline Rouard, Fabien Garnier, Jeremy Leraut, Margaux Lepainteur, Lalaina Rahajamananav, Jeanne Languepin, Marie-Cécile Ploy, Nadège Bourgeois-Nicolaos, Florence Doucet-Populaire

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