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 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.
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Maugeri Institute, IRCCS Tradate 21049, Italy. giovannibattista.migliori@icsmaugeri.it.
Giovanni Battista
GB
Migliori
Department of Infectious Diseases, Galliera Hospital, Genoa 16128, Italy. pontals@yahoo.com.
Emanuele
E
Pontali
Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy. gsotgiu@uniss.it.
Giovanni
G
Sotgiu
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Maugeri Institute, IRCCS Tradate 21049, Italy. rosella.centis@icsmaugeri.it.
Rosella
R
Centis
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Maugeri Institute, IRCCS Tradate 21049, Italy. liadambrosio59@gmail.com.|Public Health Consulting Group, Lugano CH-6904, Switzerland. liadambrosio59@gmail.com.
Lia
L
D'Ambrosio
Division of Infection, Royal London Hospital, Barts Health NHS Trust, 80 Newark Street, London E1 2ES, UK. simon.tiberi@bartshealth.nhs.uk.
Simon
S
Tiberi
Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna 40138, Italy. mtadolini@hotmail.com.
Marina
M
Tadolini
Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia 06129, Italy. susanna.esposito@unimi.it.|Pediatric Highly Intensity Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy. susanna.esposito@unimi.it.
Susanna
S
Esposito
D000995:Antitubercular Agents / Q000627:therapeutic use*; D064687:Diarylquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010080:Oxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
D000995:Antitubercular Agents; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline
MDR-TB; XDR-TB; bedaquiline; delamanid; effectiveness; safety; tolerability