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Home NEWS Science News Chemistry

International consensus highlights the importance of molecular testing for antibiotic resistance in tuberculosis management

Bioengineer by Bioengineer
April 14, 2023
in Chemistry
Reading Time: 5 mins read
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X-Ray from a TB patient
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A multidisciplinary group of tuberculosis experts from the TBnet and RESIST-TB networks have reached a consensus on key issues related to the molecular prediction of Mycobacterium tuberculosis antibiotic sensitivity or resistance and its clinical implications. The consensus document provides guidance for the design of therapeutic regimens and the optimization of treatments, and is intended to help clinicians manage tuberculosis patients. The paper, published in The Lancet Infectious Diseases and led by Dr José Domínguez from the Germans Trias i Pujol Research Institute (IGTP), is an update of a similar statement made in 2016. The publication presents a review of the current tools to rapidly identify resistance to drugs used in the treatment of tuberculosis.

X-Ray from a TB patient

Credit: INNOVA4TB

A multidisciplinary group of tuberculosis experts from the TBnet and RESIST-TB networks have reached a consensus on key issues related to the molecular prediction of Mycobacterium tuberculosis antibiotic sensitivity or resistance and its clinical implications. The consensus document provides guidance for the design of therapeutic regimens and the optimization of treatments, and is intended to help clinicians manage tuberculosis patients. The paper, published in The Lancet Infectious Diseases and led by Dr José Domínguez from the Germans Trias i Pujol Research Institute (IGTP), is an update of a similar statement made in 2016. The publication presents a review of the current tools to rapidly identify resistance to drugs used in the treatment of tuberculosis.

Tuberculosis (TB) remains a global public health threat. Despite the existence of antimicrobial regimens against the disease, the treatment is still difficult to design, administer and monitor. The latest World Health Organisation (WHO) report reveals that 1.6 million people worldwide died from the disease in 2021. In the countries of the European Economic Area, TB also causes significant human and economic losses, with an incidence of 9.5 per 100,000 people. Most worrying, however, is the growing resistance to the agents used to cure it. An estimated 450,000 people develop resistance to rifampicin each year. To control TB and minimise the emergence of resistance, the researchers of this study consider it essential, among other factors, to optimise the composition of the therapeutic regimen.

Although culture-based detection methods are considered the gold standard for antibiotic sensitivity testing, molecular methods provide rapid information on M. tuberculosis mutations associated with antibiotic resistance. The authors believe it is necessary to implement these molecular tests to predict potential resistance. The identification of mutations in clinical isolates has major implications for the treatment of patients with multidrug-resistant TB, especially when it is not available.

The consensus document promoted by the TBnet and RESIST-TB networks has been led by IGTP researchers, with the participation of clinicians, microbiologists, molecular biologists and clinical epidemiologists. The document provides key questions of clinical implication on the molecular prediction of susceptibility or drug resistance to M. tuberculosis. Dr José Domínguez, member of the TBnet Steering Committee and co-leader of the IGTP research group on Innovation in Respiratory Infections and Tuberculosis Diagnosis, states that “the rapid detection of mutations that confer resistance to anti-tuberculosis drugs is key to apply the appropriate treatment and improve the optimisation of results”.

International members of the two consortia led by the Catalan group, INNOVA4TB and ADVANCE-TB, have also collaborated in the development of the document. “In my opinion, the strength of this document is that it has been elaborated with the contributions of several researchers from different countries and with different expertise”, says Dr Domínguez, adding that “this document will help clinicians to better manage their TB patients”.



Journal

The Lancet Infectious Diseases

DOI

10.1016/S1473-3099(22)00875-1

Method of Research

Literature review

Subject of Research

Human tissue samples

Article Title

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement

Article Publication Date

28-Feb-2023

COI Statement

Declaration of interests JD reports a technology licence to GenID (Germany), and honoraria for lectures from Oxford Immunotec (UK). EC reports support for attendance, accommodation, and travel for ECCMID 2022, Lisboa from European Society of Clinical Microbiology and Infectious Diseases (ESCMID), for annual ERL-TB net meetings from ERL-TB net (Network of National Reference Centers for Tuberculosis in Europe), and for the annual congress 2022, Bologna, from the European Society for Mycobacteriology; is a member of the Executive committee of ESCMID; and is chair of the subcommittee for antimycobacterial agents of EUCAST (European Committee on Antimicrobial Susceptibility Testing). MRF reports grants or contracts from NIH/NIAID (5R01AI155765 and 5R21AI154089) and consulting fees (paid to them) from FIND. LG is a member (unpaid) of the data safety monitoring board for the XACT-19 clinical trial in University of Cape Town, Cape Town, South Africa, and is co-principal investigator of two phase 3 clinical trials on shorter treatment for MDR-TB (endTB and endTB-Q), funded by Unitaid. BL reports grants or contracts from European Union, German Ministry for Education and Research (BMBF), Kultusministerkonferenz, German Centre for Infection Research, and Helmholtz Association, and unpaid leadership or fiduciary roles for DZIF IAB, DZIF Steering Committee transplant Cohort, and TBnet chair Epidemiology. SN reports support for this manuscript (eg, funding, provision of study materials, medical writing, and article processing charges) from BMBF (German Center for Infection Research), DFG (Excellenz Cluster Precision Medicine in Chronic Inflammation EXC 2167), and Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG), and consulting fees from Illumina advisory board in 2022. NV reports grants or contracts for a study on bedaquiline from Janssen. CRH reports grants or contracts from NIH/NIAID (R01AI134430, DAA3-19-65672, R01AI147316 U01AI152980, and R01AI146555), and Centers for Disease Control and Prevention (NU38PS004651); consulting fees from Otsuka Pharmaceuticals; participation on a data safety monitoring board for SODUCU (PanACEA Sutezolid Dose-finding and Combination Evaluation), BEAT-Tuberculosis (Building Evidence for Advancing New treatment for tuberculosis), DECODE (PanACEA Delpazolid Dose-finding and Combination Development), and Médecins Sans Frontières; and a leadership or fiduciary role from the International Union Against Tuberculosis and Lung Diseases. CLa reports support for the present manuscript (eg, funding, provision of study materials, medical writing, and article processing charges) from DZIF (German Center of Infection Research); consulting fees from a consultation service to INSMED, a company that produced liposomal amikacin as an inhalative suspension for the treatment of non-tuberculous mycobacteria pulmonary disease (outside of the scope of this work); speakers’ honoraria from Insmed, Gilead, and Janssen (all outside of the scope of this work); is a member of the data safety board of trials from Médecins Sans Frontières (outside of the scope of this work); is supported by the German Center for Infection Research (DZIF); and acknowledges funding from the European Commission (anTBiotic EU-H2020 733079, ClicTB EDCTP2 RIA2017T-2030, stool4TB EDCTP2 RIAD2018-2511, and UNITE4TB EU-IMI 101007873). All other authors declare no competing interests.

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