Combined Use of Delamanid and Bedaquiline to Treat Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: A Systematic Review

The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic...

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Published in:International journal of molecular sciences Vol. 18; no. 2; p. 341
Main Authors: Migliori, Giovanni, Pontali, Emanuele, Sotgiu, Giovanni, Centis, Rosella, D’Ambrosio, Lia, Tiberi, Simon, Tadolini, Marina, Esposito, Susanna
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 07.02.2017
MDPI
Subjects:
Antitubercular Agents - therapeutic use
Diarylquinolines - administration & dosage
Diarylquinolines - adverse effects
Diarylquinolines - therapeutic use
Drug resistance
Drug Therapy, Combination
Extensively Drug-Resistant Tuberculosis - diagnosis
Extensively Drug-Resistant Tuberculosis - drug therapy
Extensively Drug-Resistant Tuberculosis - epidemiology
Extensively Drug-Resistant Tuberculosis - microbiology
Humans
Multidrug resistant organisms
Mycobacterium
Nitroimidazoles - administration & dosage
Nitroimidazoles - adverse effects
Nitroimidazoles - therapeutic use
Oxazoles - administration & dosage
Oxazoles - adverse effects
Oxazoles - therapeutic use
Review
Studies
Treatment Outcome
Tuberculosis
Tuberculosis, Multidrug-Resistant - diagnosis
Tuberculosis, Multidrug-Resistant - drug therapy
Tuberculosis, Multidrug-Resistant - epidemiology
Tuberculosis, Multidrug-Resistant - microbiology
effectiveness
safety
tolerability
MDR-TB
delamanid
XDR-TB
bedaquiline
ISSN:1422-0067, 1661-6596, 1422-0067
Online Access:Get full text
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Abstract The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold.
AbstractList The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold.
Author D’Ambrosio, Lia
Centis, Rosella
Tiberi, Simon
Migliori, Giovanni
Pontali, Emanuele
Tadolini, Marina
Sotgiu, Giovanni
Esposito, Susanna
AuthorAffiliation 4 Public Health Consulting Group, Lugano CH-6904, Switzerland
6 Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna 40138, Italy; mtadolini@hotmail.com
7 Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia 06129, Italy
5 Division of Infection, Royal London Hospital, Barts Health NHS Trust, 80 Newark Street, London E1 2ES, UK; simon.tiberi@bartshealth.nhs.uk
3 Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy; gsotgiu@uniss.it
1 World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Maugeri Institute, IRCCS Tradate 21049, Italy; giovannibattista.migliori@icsmaugeri.it (G.B.M.); rosella.centis@icsmaugeri.it (R.C.); liadambrosio59@gmail.com (L.D.)
2 Department of Infectious Diseases, Galliera Hospital, Genoa 16128, Italy; pontals@yahoo.com
8 Pediatric Highly In
AuthorAffiliation_xml – name: 1 World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Maugeri Institute, IRCCS Tradate 21049, Italy; giovannibattista.migliori@icsmaugeri.it (G.B.M.); rosella.centis@icsmaugeri.it (R.C.); liadambrosio59@gmail.com (L.D.)
– name: 8 Pediatric Highly Intensity Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
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– name: 3 Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy; gsotgiu@uniss.it
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– name: 5 Division of Infection, Royal London Hospital, Barts Health NHS Trust, 80 Newark Street, London E1 2ES, UK; simon.tiberi@bartshealth.nhs.uk
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– name: 6 Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna 40138, Italy; mtadolini@hotmail.com
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Issue 2
Keywords effectiveness
safety
tolerability
MDR-TB
delamanid
XDR-TB
bedaquiline
Language English
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Snippet The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB)....
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StartPage 341
SubjectTerms Antitubercular Agents - therapeutic use
Diarylquinolines - administration & dosage
Diarylquinolines - adverse effects
Diarylquinolines - therapeutic use
Drug resistance
Drug Therapy, Combination
Extensively Drug-Resistant Tuberculosis - diagnosis
Extensively Drug-Resistant Tuberculosis - drug therapy
Extensively Drug-Resistant Tuberculosis - epidemiology
Extensively Drug-Resistant Tuberculosis - microbiology
Humans
Multidrug resistant organisms
Mycobacterium
Nitroimidazoles - administration & dosage
Nitroimidazoles - adverse effects
Nitroimidazoles - therapeutic use
Oxazoles - administration & dosage
Oxazoles - adverse effects
Oxazoles - therapeutic use
Review
Studies
Treatment Outcome
Tuberculosis
Tuberculosis, Multidrug-Resistant - diagnosis
Tuberculosis, Multidrug-Resistant - drug therapy
Tuberculosis, Multidrug-Resistant - epidemiology
Tuberculosis, Multidrug-Resistant - microbiology
Title Combined Use of Delamanid and Bedaquiline to Treat Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: A Systematic Review
URI https://www.ncbi.nlm.nih.gov/pubmed/28178199
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https://pubmed.ncbi.nlm.nih.gov/PMC5343876
Volume 18
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