ArticleEBioMedicine2016
A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 46 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
- Bacterial Factors That Predict Relapse after Tuberculosis Therapy.The New England journal of medicine · 2018Trial
- Harnessing the gut microbiome to combat tuberculosis: a technological and clinical review.Frontiers in cellular and infection microbiology · 2026Review
- 3D bioprinting for the construction of drug testing models-development strategies and regulatory concerns.Frontiers in bioengineering and biotechnology · 2025Review
- Meropenem-vaborbactam restoration of first-line drug efficacy and comparison of meropenem-vaborbactam-moxifloxacin versus BPaL MDR-TB regimen.International journal of antimicrobial agents · 2023Article
- Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments.Antimicrobial agents and chemotherapy · 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
- Pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs: An evaluation ofFrontiers in pharmacology · 2022Review
- Cefdinir and β-Lactamase Inhibitor Independent Efficacy AgainstFrontiers in pharmacology · 2021Article
- Repurposing Cefazolin-Avibactam for the Treatment of Drug ResistantFrontiers in pharmacology · 2021Article
- Tackling Current Biomedical Challenges With Frontier Biofabrication and Organ-On-A-Chip Technologies.Frontiers in bioengineering and biotechnology · 2021Review
- Evaluation of Ceftriaxone Plus Avibactam in an Intracellular Hollow Fiber Model of Tuberculosis: Implications for the Treatment of Disseminated and Meningeal Tuberculosis in Children.The Pediatric infectious disease journal · 2020Article
- Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.The Journal of antimicrobial chemotherapy · 2020Article
- Detectable prednisolone is delayed in pericardial fluid, compared with plasma of patients with tuberculous pericarditis: A pilot study.International journal of cardiology. Heart & vasculature · 2019Article
- Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs.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
- 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
- Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis.American journal of respiratory and critical care medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children≤6years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.