TY - JOUR
T1 - Efficacy and tolerability of concomitant use of bedaquiline and delamanid for multidrug- and extensively drug-resistant tuberculosis
T2 - a systematic review and meta-analysis
AU - Holmgaard, Freja Breth
AU - Guglielmetti, Lorenzo
AU - Lillebaek, Troels
AU - Andersen, Åse Bengaard
AU - Wejse, Christian
AU - Dahl, Victor Naestholt
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2023/4/3
Y1 - 2023/4/3
N2 - The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.
AB - The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.
KW - Antitubercular Agents/adverse effects
KW - Diarylquinolines/adverse effects
KW - Extensively Drug-Resistant Tuberculosis/drug therapy
KW - Humans
KW - Nitroimidazoles/adverse effects
KW - Oxazoles/adverse effects
KW - Treatment Outcome
KW - Tuberculosis, Multidrug-Resistant/drug therapy
KW - tuberculosis
KW - systematic review
KW - bedaquiline
KW - delamanid
KW - drug resistance
UR - http://www.scopus.com/inward/record.url?scp=85152159009&partnerID=8YFLogxK
U2 - 10.1093/cid/ciac876
DO - 10.1093/cid/ciac876
M3 - Review
C2 - 36331978
SN - 1058-4838
VL - 76
SP - 1328
EP - 1337
JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
IS - 7
ER -