ArticleScientific reports2017
Pharmacokinetic-Pharmacodynamic modelling of intracellular Mycobacterium tuberculosis growth and kill rates is predictive of clinical treatment duration.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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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.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Fast-growing intracellular Mycobacterium tuberculosis populations evade antibiotic treatment.Nature communications · 2026Article
- Uncertainty undermines the validity of antimicrobial pharmacodynamics.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Drug Design and Delivery for Intracellular Bacteria: Emerging Paradigms.Drug development research · 2025Review
- Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare.The Journal of antimicrobial chemotherapy · 2024Review
- Breaking barriers: The potential of nanosystems in antituberculosis therapy.Bioactive materials · 2024Review
- High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.PLoS computational biology · 2023Article
- A Quantitative Method for the Study of HIV-1 and Mycobacterium tuberculosis Coinfection.The Journal of infectious diseases · 2023Article
- Article
- The LEAP Process: Streamlining the Development of Long-Acting Products and Formulations for Infectious Diseases.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Bacterial growth dynamics and pharmacokinetic-pharmacodynamic relationships of rifampicin and bedaquiline in BALB/c mice.British journal of pharmacology · 2022Article
- vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding.BMC bioinformatics · 2022Article
- Intracellular Accumulation of Novel and Clinically Used TB Drugs Potentiates Intracellular Synergy.Microbiology spectrum · 2021Article
- Live-imaging rate-of-kill compound profiling for Chagas disease drug discovery with a new automated high-content assay.PLoS neglected tropical diseases · 2021Article
- Gastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis.Nature communications · 2021Article
- A Review of Using Mathematical Modeling to Improve Our Understanding of Bacteriophage, Bacteria, and Eukaryotic Interactions.Frontiers in microbiology · 2021Review
- Intracellular Pharmacodynamic Modeling Is Predictive of the Clinical Activity of Fluoroquinolones against Tuberculosis.Antimicrobial agents and chemotherapy · 2019Article
- Using Mycobacterium tuberculosis Single-Nucleotide Polymorphisms To Predict Fluoroquinolone Treatment Response.Antimicrobial agents and chemotherapy · 2019Article
- Intracellular PD Modelling (Pharmaceutics · 2019Article
- Quantitative assessment of the activity of antituberculosis drugs and regimens.Expert review of anti-infective therapy · 2019Review
- A novel derivative of the fungal antimicrobial peptide plectasin is active against Mycobacterium tuberculosis.Tuberculosis (Edinburgh, Scotland) · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages. Through use of this pharmacokinetic-pharmacodynamic (PK-PD) approach we demonstrate that the killing dynamics of the intracellular Mtb sub-population is critical to predicting clinical TB treatment duration. Integrated modelling of intracellular Mtb killing alongside conventional extracellular Mtb killing data, generates the biphasic responses typical of those described clinically. Our model supports the hypothesis that the use of higher doses of rifampicin (35 mg/kg) will significantly reduce treatment duration. Our described PK-PD approach offers a much needed decision making tool for the identification and prioritisation of new therapies which have the potential to reduce TB treatment duration.
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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.