Publications
Should isoniazid and clofazimine be used to treat multidrug-resistant tuberculosis? [reply] Institute of Tropical Medicine
Optimization of the clofazimine structure leads to a highly water-soluble C3-aminopyridinyl riminophenazine endowed with improved anti-Wnt and anti-cancer activity in vitro and in vivo KU Leuven
Multicentre study to establish interpretive criteria for clofazimine drug susceptibility testing Institute of Tropical Medicine University of Antwerp
OBJECTIVE: To conduct a multicentre study to establish the critical concentration (CC) for clofazimine (CFZ) for drug susceptibility testing (DST) of Mycobacterium tuberculosis on the MGIT (TM) 960 (TM) system using the distribution of minimum inhibitory concentrations (MIC) and genotypic analyses of Rv0678 mutations.
DESIGN: In phase I of the study, the MIC distribution of laboratory strains (H37Rv and in vitro-selected Rv0678 ...
Unexpected high prevalence of resistance-associated Rv0678 variants in MDR-TB patients without documented prior use of clofazimine or bedaquiline Institute of Tropical Medicine
OBJECTIVES: Resistance-associated variants (RAVs) in Rv0678, a regulator of the MmpS5-MmpL5 efflux pump, have been shown to lead to increased MICs of bedaquiline (2- to 8- fold) and clofazimine (2- to 4-fold). The prevalence of these Rv0678 RAVs in clinical isolates and their impact on treatment outcomes are important factors to take into account in bedaquiline treatment guidelines.
METHODS: Baseline isolates from two bedaquiline ...
Bedaquiline- and clofazimine- selected Mycobacterium tuberculosis mutants: further insights on resistance driven largely by Rv0678 Institute of Tropical Medicine
Drug-resistant tuberculosis is a serious global health threat. Bedaquiline (BDQ) is a relatively new core drug, targeting the respiratory chain in Mycobacterium tuberculosis (Mtb). While mutations in the BDQ target gene, atpE, are rare in clinical isolates, mutations in the Rv0678 gene, a transcriptional repressor regulating the efflux pump MmpS5-MmpL5, are increasingly observed, and have been linked to worse treatment outcomes. Nevertheless, ...
Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis University of Antwerp
Short, highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis Institute of Tropical Medicine
A multimethod, multicountry evaluation of breakpoints for bedaquiline resistance determination Institute of Tropical Medicine
Criteria defining bedaquiline resistance for tuberculosis have been proposed addressing an emerging concern. We evaluated bedaquiline phenotypic drug susceptibility testing (pDST) criteria using drug-resistant tuberculosis clinical isolates tested at five reference laboratories. Isolates were tested at the proposed bedaquiline MGIT960 and 7H11 agar proportion (AP) critical concentrations and also at higher dilutions. The epidemiological ...
Injectables' key role in rifampicin-resistant tuberculosis shorter treatment regimen outcomes Institute of Tropical Medicine
Background
Since a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the ...