An assay toolkit for anti-tuberculosis drugs in the hollow fiber system

  • iScience. 2026 Mar 10;29(4):115292. doi: 10.1016/j.isci.2026.115292.
Fernando Sanz-García  1 ,  Dominique Ndjogou  2 ,  Diana A Aguilar-Ayala  1 ,  Maxime R Eveque-Mourroux  2 ,  Ana Benítez  1 ,  Sergio Aznar  1 ,  Nuria Isach-Traver  1 ,  Alfonso Mendoza-Losana  3 ,  Nicolas Willand  2 ,  Ainhoa Lucía  1  4 ,  Santiago Ramón-García  1  4  5 ,  ERA4TB consortium
Affiliations
  • 1. Department of Microbiology, Paediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain.
  • 2. University Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, 59000 Lille, France.
  • 3. Departamento de Bioingeniería, Universidad Carlos III de Madrid (UC3M), 28903 Madrid, Spain.
  • 4. Spanish Network for Research on Respiratory Diseases (CIBERES), Carlos III Health Institute, 28029 Madrid, Spain.
  • 5. Research & Development Agency of Aragón Foundation (Fundación ARAID), 50018 Zaragoza, Spain.
PMID: 41940336 DOI: 10.1016/j.isci.2026.115292
Abstract

The hollow-fiber system for tuberculosis (HFS-TB) is an in vitro pharmacokinetic/pharmacodynamic (PKPD) tool qualified by the European Medicines Agency to support anti-TB drug development. It can simulate PK parameters of antimicrobials and feed in silico models to inform phase II/III clinical trials. Yet, its implementation is challenging due to lack of consolidated technical guidelines, such as the compatibility of drugs with the most commonly used types of HFS-TB cartridges. Herein, we uncovered the compatibility of 10 anti-TB drugs alone: bedaquiline, clarithromycin, delamanid, ethambutol, isoniazid, linezolid, moxifloxacin, pretomanid, rifampicin, and rifapentine; and of a combination, bedaquiline-pretomanid-linezolid. The most hydrophilic compounds were within the compatibility range with all fibers; whereas the lipophilic ones required adjustments to be used in the system. Also, polysulfone and cellulose fibers were the most suitable for the tested drugs. Our data strengthen the importance of these preliminary studies and provide a useful toolkit toward wider HFS-TB implementation.

Keywords
Biological sciences; Health sciences; Medical microbiology; Medicine; Microbiology; Natural sciences.
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