ArticleAntimicrobial agents and chemotherapy2015
Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03378427 (Prospective Cohort Study on Patients With Tedizolid Prolonged Therapy for Orthopedic Device Infections), which is not on this map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Prospective Cohort Study on Patients With Tedizolid Prolonged Therapy for Orthopedic Device Infections
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.The Journal of antimicrobial chemotherapy · 2018Pooled it
- Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.EBioMedicine · 2015Trial
- Efficacy, safety, tolerability and population pharmacokinetics of tedizolid, a novel antibiotic, in Latino patients with acute bacterial skin and skin structure infections.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesTrial
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Deciphering linezolid-induced hematologic toxicity: Targeting TOP2A and TOP2B via its primary metabolite PNU142586.Science advances · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Linezolid and tedizolid adverse effects: a review on serotonin syndrome, myelosuppression, neuropathies, and lactic acidosis.Antimicrobial stewardship & healthcare epidemiology : ASHE · 2025Review
- Study on the Efficacy and Safety of Tedizolid in Japanese Patients.Antibiotics (Basel, Switzerland) · 2024Article
- Oxazolidinone antibiotics impairAntimicrobial agents and chemotherapy · 2024Article
- Severe Optic Neuropathy Induced by Very Prolonged Tedizolid as Suppressive Therapy: Description of a Case Report and Implication for Better Assessment.Open forum infectious diseases · 2024Article
- The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature.Antibiotics (Basel, Switzerland) · 2023Review
- Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections.Antimicrobial agents and chemotherapy · 2023Article
- Pharmacokinetics of Ceftazidime-Avibactam in Combination with Aztreonam (COMBINE) in a Phase 1, Open-Label Study of Healthy Adults.Antimicrobial agents and chemotherapy · 2022Article
- The Novel Oxazolidinone TBI-223 Is Effective in Three Preclinical Mouse Models of Methicillin-Resistant Staphylococcus aureus Infection.Microbiology spectrum · 2022Article
- Real-World Use of Tedizolid Phosphate for 28 Days or More: A Case Series Describing Tolerability and Clinical Success.Open forum infectious diseases · 2022Article
- MRSA compendium of epidemiology, transmission, pathophysiology, treatment, and prevention within one health framework.Frontiers in microbiology · 2022Review
- Minocycline intra-bacterial pharmacokinetic hysteresis as a basis for pharmacologic memory and a backbone for once-a-week pan-tuberculosis therapy.Frontiers in pharmacology · 2022Article
- In vitro Susceptibility of Nontuberculous Mycobacteria to Tedizolid.Infection and drug resistance · 2022Article
- Safety of Tedizolid as Suppressive Antimicrobial Therapy for Patients With Complex Implant-Associated Bone and Joint Infection due to Multidrug-Resistant Gram-Positive Pathogens: Results From the TediSAT Cohort Study.Open forum infectious diseases · 2021Article
- Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid to cause similar side effects, nonclinical and pharmacokinetic assessments were conducted. In isolated rat heart mitochondria, tedizolid inhibited MPS more potently than did linezolid (average [± standard error of the mean] 50% inhibitory concentration [IC50] for MPS of 0.31 ± 0.02 μM versus 6.4 ± 1.2 μM). However, a rigorous 9-month rat study comparing placebo and high-dose tedizolid (resulting in steady-state area under the plasma concentration-time curve values about 8-fold greater than those with the standard therapeutic dose in humans) showed no evidence of neuropathy. Additional studies explored why prolonged, high-dose tedizolid did not cause these mitochondriopathic side effects despite potent MPS inhibition by tedizolid. Murine macrophage (J774) cell fractionation studies found no evidence of a stable association of tedizolid with eukaryotic mitochondria. Monte Carlo simulations based on population pharmacokinetic models showed that over the course of a dosing interval using standard therapeutic doses, free plasma concentrations fell below the respective MPS IC50 in 84% of tedizolid-treated patients (for a median duration of 7.94 h) and 38% of linezolid-treated patients (for a median duration of 0 h). Therapeutic doses of tedizolid, but not linezolid, may therefore allow for mitochondrial recovery during antibacterial therapy. The overall results suggest that tedizolid has less potential to cause myelosuppression and neuropathy than that of linezolid during prolonged treatment courses. This, however, remains a hypothesis that must be confirmed in clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.