The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs
| Autor: | Corné P. de Vogel, Aart van der Meijden, Jurriaan E. M. de Steenwinkel, Irma A. J. M. Bakker-Woudenberg, Annelies Verbon, Hannelore I. Bax |
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| Přispěvatelé: | Internal Medicine, Medical Microbiology & Infectious Diseases |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Drug Tuberculosis Genotype media_common.quotation_subject 030106 microbiology Immunology Antitubercular Agents Microbial Sensitivity Tests Drug resistance Pharmacology Microbiology Mycobacterium tuberculosis 03 medical and health sciences SDG 3 - Good Health and Well-being Drug Discovery Drug Resistance Bacterial medicine Humans Ethambutol media_common Microbial Viability Dose-Response Relationship Drug biology business.industry Isoniazid Drug Synergism biology.organism_classification medicine.disease Bacterial Load Kinetics Infectious Diseases Streptomycin Drug Therapy Combination business Rifampicin medicine.drug |
| Zdroj: | Tuberculosis, 105, 80-85. Churchill Livingstone |
| ISSN: | 1873-281X 1472-9792 |
| Popis: | Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. |
| Databáze: | OpenAIRE |
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