ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018
Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Systematic and quantitative analyses of hollow fiber model ofMicrobiology spectrum · 2026Pooled it
- Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review.PLoS pathogens · 2024Pooled it
- Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens forAntimicrobial agents and chemotherapy · 2026Article
- Novel regimens for treatment ofbioRxiv : the preprint server for biology · 2026Article
- Preclinical pharmacokinetics/pharmacodynamics studies defining the role of ethambutol inAntimicrobial agents and chemotherapy · 2026Article
- Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease.The Journal of antimicrobial chemotherapy · 2026Article
- Sulbactam-Durlobactam Plus Ceftriaxone Dosing and Novel Treatment Regimens forbioRxiv : the preprint server for biology · 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
- Ceftriaxone Efficacy for Mycobacterium avium Complex Lung Disease in the Hollow Fiber and Translation to Sustained Sputum Culture Conversion in Patients.The Journal of infectious diseases · 2024Article
- Antibacterial action of penicillin againstIJTLD open · 2024Article
- Application of the Hollow-Fiber Infection Model to Personalized Precision Dosing of Isoniazid in a Clinical Setting.Journal of Korean medical science · 2024Article
- Nouveau short-course therapy and morphism mapping for clinical pulmonaryAntimicrobial agents and chemotherapy · 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
- High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.PLoS computational biology · 2023Article
- Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.The Journal of antimicrobial chemotherapy · 2022Article
- 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
- Bacterial load slopes represent biomarkers of tuberculosis therapy success, failure, and relapse.Communications biology · 2021Article
- Dynamic imaging in patients with tuberculosis reveals heterogeneous drug exposures in pulmonary lesions.Nature medicine · 2020Article
- Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.The Journal of antimicrobial chemotherapy · 2020Article
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8 authors.
Funding
Abstract
Background: A major challenge in medicine is translation of preclinical model findings to humans, especially therapy duration. One major example is recent shorter-duration therapy regimen failures in tuberculosis. Methods: We used set theory mapping to develop a computational/modeling framework to map the time it takes to extinguish the Mycobacterium tuberculosis population on chemotherapy from multiple hollow fiber system model of tuberculosis (HFS-TB) experiments to that observed in patients. The predictive accuracy of the derived translation transformations was then tested using data from 108 HFS-TB Rapid Evaluation of Moxifloxacin in Tuberculosis (REMoxTB) units, including 756 colony-forming units (CFU)/mL. Derived transformations, and Latin hypercube sampling-guided simulations were used to predict cure and relapse after 4 and 6 months of therapy. Outcomes were compared to observations, in 1932 patients in the REMoxTB clinical trial. Results: HFS-TB serial bacillary burden and serial sputum data in the derivation dataset formed a structure-preserving map. Bactericidal effect was mapped with a single step transformation, while the sterilizing effect was mapped with a 3-step transformation function. Using the HFS-TB REMoxTB data, we accurately predicted the proportion of patients cured in the 4-month REMoxTB clinical trial. Model-predicted vs clinical trial observations were (i) the ethambutol arm (77.0% [95% confidence interval {CI}, 74.4%-79.6%] vs 77.7% [95% CI, 74.3%-80.9%]) and (ii) the isoniazid arm (76.4% [95% CI, 73.9%-79.0%] vs 79.5% [95% CI, 76.1%-82.5%]). Conclusions: We developed a method to translate duration of therapy outcomes from preclinical models to tuberculosis patients.
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