ArticleThe Journal of infectious diseases2021
Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis.
Article in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06590428 (Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis), which is not on this map. Cited by 18 papers.
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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.
Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis
Who cites it
18 citing papers in PubMed.
- Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Model-based translation of the PKPD-relationship for linezolid and vancomycin on methicillin-resistant Staphylococcus aureus: from in vitro time-kill experiments to a mouse pneumonia model.The Journal of antimicrobial chemotherapy · 2025Article
- Bufei Jiedu Formula enhances CD40 activation and macrophage polarization to eliminate intracellular MRSA persisters.Frontiers in immunology · 2025Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen.Nature communications · 2024Article
- Efficacy of linezolid in the treatment of tuberculous meningitis: a meta-analysis.Archives of medical science : AMS · 2024Article
- Contezolid can replace linezolid in a novel combination with bedaquiline and pretomanid in a murine model of tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
- Fluoroquinolone-resistant latent tuberculosis infection: A literature review and case series of 5 patients treated with linezolid monotherapy.Journal of clinical tuberculosis and other mycobacterial diseases · 2023Article
- Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis.Antibiotics (Basel, Switzerland) · 2023Article
- Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents.Cell · 2023Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- DynamicNature communications · 2022Article
- Linezolid Exposure Is Associated with Cytopenias in Patients Treated for Multidrug-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study.The Journal of antimicrobial chemotherapy · 2022Observational
- Article
- Developing New Drugs for Mycobacterium tuberculosis Therapy: What Information Do We Get from Preclinical Animal Models?Antimicrobial agents and chemotherapy · 2020Article
- Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis.Antimicrobial agents and chemotherapy · 2020Article
- Preserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis Model.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundLinezolid (LZD) is bactericidal against Mycobacterium tuberculosis, but it has treatment-limiting toxicities. A better understanding of exposure-response relationships governing LZD efficacy and toxicity will inform dosing strategies. Because in vitro monotherapy studies yielded conflicting results, we explored LZD pharmacokinetic/pharmacodynamic (PK/PD) relationships in vivo against actively and nonactively multiplying bacteria, including in combination with pretomanid.
methodsLinezolid multidose pharmacokinetics were modeled in mice. Dose-fractionation studies were performed in acute (net bacterial growth) and chronic (no net growth) infection models. In acute models, LZD was administered alone or with bacteriostatic or bactericidal pretomanid doses. Correlations between PK/PD parameters and lung colony-forming units (CFUs) and complete blood counts were assessed.
resultsOverall, time above minimum inhibitory concentration (T>MIC) correlated best with CFU decline. However, in growth-constrained models (ie, chronic infection, coadministration with pretomanid 50 mg/kg per day), area under the concentration-time curve over MIC (AUC/MIC) had similar explanatory power. Red blood cell counts correlated strongly with LZD minimum concentration (Cmin).
conclusionsAlthough T>MIC was the most consistent correlate of efficacy, AUC/MIC was equally predictive when bacterial multiplication was constrained by host immunity or pretomanid. In effective combination regimens, administering the same total LZD dose less frequently may be equally effective and cause less Cmin-dependent toxicity.
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