ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2016
Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
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- Multicentre controlled open randomised clinical trial to assess efficacy and safety of an anti-tuberculosis drug combination based on optimised-dose rifampicin, optimised-dose moxifloxacin and optimised-dose linezolid for TB: the RML-TB trial protocol.BMJ open respiratory research · 2025Article
- Examining effective monotherapy hypothesis for TB therapy failure and resistance emergence.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2024Article
- PhysiBoSS 2.0: a sustainable integration of stochastic Boolean and agent-based modelling frameworks.NPJ systems biology and applications · 2023Article
- Hollow-fibre system model of tuberculosis reproducibility and performance specifications for best practice in drug and combination therapy development.The Journal of antimicrobial chemotherapy · 2023Article
- Potency of the novel PolC DNA polymerase inhibitor CRS0540 in a disseminated Listeria monocytogenes intracellular hollow-fibre model.The Journal of antimicrobial chemotherapy · 2022Article
- Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis.Frontiers in pharmacology · 2022Article
- Transcriptome signature of cell viability predicts drug response and drug interaction inCell reports methods · 2021Article
- Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.Antibiotics (Basel, Switzerland) · 2021Review
- Mycobacterium tuberculosis sterilizing activity of faropenem, pyrazinamide and linezolid combination and failure to shorten the therapy duration.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2021Article
- Repurposing Cefazolin-Avibactam for the Treatment of Drug ResistantFrontiers in pharmacology · 2021Article
- Multidrug-resistant strains ofVeterinary world · 2020Article
- CombiANT: Antibiotic interaction testing made easy.PLoS biology · 2020Article
- Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.The Journal of antimicrobial chemotherapy · 2020Article
- Colistin Combined With Tigecycline: A Promising Alternative Strategy to CombatFrontiers in microbiology · 2019Article
- Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Gatifloxacin Pharmacokinetics/Pharmacodynamics-based Optimal Dosing for Pulmonary and Meningeal Multidrug-resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Multiparameter Responses to Tedizolid Monotherapy and Moxifloxacin Combination Therapy Models of Children With Intracellular Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Assessment of the Additional Value of Verapamil to a Moxifloxacin and Linezolid Combination Regimen in a Murine Tuberculosis Model.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundNo treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need.
methodsWe examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression.
resultsThe full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively.
conclusionsWe identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children.
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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.