PMID- 33736710
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 2049-9957 (Electronic)
IS  - 2095-5162 (Print)
IS  - 2049-9957 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Mar 19
TI  - Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant 
      tuberculosis in China: focus on the safety.
PG  - 32
LID - 10.1186/s40249-021-00819-2 [doi]
LID - 32
AB  - BACKGROUND: World Health Organization recommends countries introducing new drug 
      and short treatment regimen for drug resistant tuberculosis (DR-TB) should 
      develop and implement a system for active pharmacovigilance that allows for 
      detection, reporting and management of adverse events. The aim of the study is to 
      evaluate the frequency and severity of adverse events (AEs) of 
      bedaquiline-containing regimen in a cohort of Chinese patients with 
      multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active 
      drug safety monitoring (aDSM) system of New Drug Introduction and Protection 
      Program (NDIP). METHODS: AEs were prospectively collected with demographic, 
      bacteriological, radiological and clinical data from 54 sites throughout China at 
      patient enrollment and during treatment between February, 2018 and December, 
      2019. This is an interim analysis including patients who are still on treatment 
      and those that have completed treatment. A descriptive analysis was performed on 
      the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 
      1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 
      AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as 
      serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 
      [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week 
      prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 
      47.1% and 7.8%, respectively. The most frequently reported AEs were QT 
      prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading 
      to death. Out of patients with available corrected QT interval by Fridericia's 
      formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF >/= 500 ms, 
      and 15.7% (132/839) had at least one change of QTcF >/= 60 ms from baseline. 49 
      (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One 
      hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the 
      second with high occurrence. Thirty-four patients reported 43 AEs of hepatic 
      injury referred to bedaquiline, much lower than that referred to protionamide, 
      pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline 
      was generally well-tolerated with few safety concerns in this clinical patient 
      population without any new safety signal identified. The mortality rate was 
      generally low. These data inform significant positive effect to support the WHO 
      recent recommendations for the wide use of bedaquiline.
FAU - Gao, Jing-Tao
AU  - Gao JT
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Du, Juan
AU  - Du J
AD  - Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, People's Republic of 
      China.
FAU - Wu, Gui-Hui
AU  - Wu GH
AD  - Department of Tuberculosis, Chengdu Public Health Clinical Center, Chengdu, 
      People's Republic of China.
FAU - Pei, Yi
AU  - Pei Y
AD  - Department of Tuberculosis, Changsha Central Hospital, Changsha, People's 
      Republic of China.
FAU - Gao, Meng-Qiu
AU  - Gao MQ
AD  - Department of Tuberculosis, Beijing Chest Hospital, Capital Medical 
      University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 
      People's Republic of China.
FAU - Martinez, Leonardo
AU  - Martinez L
AD  - Division of Infectious Diseases and Geographic Medicine, School of Medicine, 
      Stanford University, Palo Alto, CA, USA.
FAU - Fan, Lin
AU  - Fan L
AD  - Department of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai, People's 
      Republic of China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, People's Republic 
      of China.
FAU - Xie, Li
AU  - Xie L
AD  - Department of Tuberculosis, Beijing Chest Hospital, Capital Medical 
      University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 
      People's Republic of China.
FAU - Chen, Yu
AU  - Chen Y
AD  - Department of Tuberculosis, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 
      People's Republic of China.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Tuberculosis, Anhui Chest Hospital, Hefei, People's Republic of 
      China.
FAU - Jin, Long
AU  - Jin L
AD  - Department of Tuberculosis, Infectious Diseases Hospital Heilongjiang Province, 
      Harbin, People's Republic of China.
FAU - Li, Guo-Bao
AU  - Li GB
AD  - Department of Tuberculosis, The Third People's Hospital of Shenzhen, Shenzhen, 
      People's Republic of China.
FAU - Zong, Pei-Lan
AU  - Zong PL
AD  - Department of Tuberculosis, Jiangxi Chest (Third People) Hospital, Nanchang, 
      People's Republic of China.
FAU - Xiong, Yu
AU  - Xiong Y
AD  - Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, People's 
      Republic of China.
FAU - Wu, Qian-Hong
AU  - Wu QH
AD  - Department of Tuberculosis, Shanxi Provincial Tuberculosis Institute, Xi'an, 
      People's Republic of China.
FAU - Li, Ming-Wu
AU  - Li MW
AD  - Department of Tuberculosis, Kunming Third People's Hospital, Kunming, People's 
      Republic of China.
FAU - Yan, Xiao-Feng
AU  - Yan XF
AD  - Department of Tuberculosis, Chongqing Public Health Medical Center, Chongqing, 
      People's Republic of China.
FAU - Miao, Yan-Fang
AU  - Miao YF
AD  - Department of Tuberculosis, The Fourth People's Hospital of Taiyuan, Taiyuan, 
      People's Republic of China.
FAU - Cai, Qing-Shan
AU  - Cai QS
AD  - Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People's 
      Republic of China.
FAU - Li, Xin-Jie
AU  - Li XJ
AD  - Department of Tuberculosis, Guangzhou Chest Hospital, Guangzhou, People's 
      Republic of China.
FAU - Bai, Da-Peng
AU  - Bai DP
AD  - Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People's Republic of 
      China.
FAU - Geng, Shu-Jun
AU  - Geng SJ
AD  - Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People's Republic 
      of China.
FAU - Yang, Guo-Li
AU  - Yang GL
AD  - Department of Tuberculosis, Tuberculosis Hospital of Jilin Province, Changchun, 
      People's Republic of China.
FAU - Tang, Pei-Jun
AU  - Tang PJ
AD  - Department of Tuberculosis, The Fifth People's Hospital of Suzhou, Infectious 
      Disease Hospital, Affiliated to Soochow University, Suzhou, People's Republic of 
      China.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, People's 
      Republic of China.
FAU - Chen, Xiao-Hong
AU  - Chen XH
AD  - Department of Tuberculosis, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, People's 
      Republic of China.
FAU - Li, Tong-Xia
AU  - Li TX
AD  - Department of Tuberculosis, Qingdao Chest Hospital, Qingdao, People's Republic of 
      China.
FAU - Cai, Cui
AU  - Cai C
AD  - Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, 
      People's Republic of China.
FAU - Zhou, Yun
AU  - Zhou Y
AD  - Department of Tuberculosis, The Second Affiliated Hospital of Hainan Medical 
      University, Haikou, People's Republic of China.
FAU - Zhuo, Ma
AU  - Zhuo M
AD  - Department of Tuberculosis, The Fourth People's Hospital of QingHai Province, 
      Xining, People's Republic of China.
FAU - Wang, Jian-Yun
AU  - Wang JY
AD  - Department of Tuberculosis, Lanzhou Pulmonary Hospital, Lanzhou, People's 
      Republic of China.
FAU - Guan, Wen-Long
AU  - Guan WL
AD  - Department of Tuberculosis, Chest Hospital of Xinjiang Uyghur Autonomous Region 
      of the PRC, Urumchi, People's Republic of China.
FAU - Xu, Lin
AU  - Xu L
AD  - Department of Tuberculosis, The Fourth People's Hospital of Ningxia Hui 
      Autonomous Region, Yinchuan, People's Republic of China.
FAU - Shi, Ji-Chan
AU  - Shi JC
AD  - Department of Tuberculosis, Wenzhou Central Hospital, Wenzhou, People's Republic 
      of China.
FAU - Shu, Wei
AU  - Shu W
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Cheng, Li-Li
AU  - Cheng LL
AD  - Beijing Innovation Alliance of TB Diagnosis and Treatment, Beijing, People's 
      Republic of China.
FAU - Teng, Fei
AU  - Teng F
AD  - Beijing Innovation Alliance of TB Diagnosis and Treatment, Beijing, People's 
      Republic of China.
FAU - Ning, Yu-Jia
AU  - Ning YJ
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Xie, Shi-Heng
AU  - Xie SH
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Sun, Yu-Xian
AU  - Sun YX
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Zhang, Li-Jie
AU  - Zhang LJ
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China.
FAU - Liu, Yu-Hong
AU  - Liu YH
AD  - Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing 
      Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, 
      Tongzhou District, Beijing, 101149, People's Republic of China. 
      liuyuhong0516@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210319
PL  - England
TA  - Infect Dis Poverty
JT  - Infectious diseases of poverty
JID - 101606645
RN  - 0 (Antitubercular Agents)
RN  - 0 (Diarylquinolines)
RN  - 78846I289Y (bedaquiline)
SB  - IM
MH  - Adult
MH  - Antitubercular Agents/administration & dosage/*adverse effects/*therapeutic use
MH  - China/epidemiology
MH  - Diarylquinolines/*adverse effects/*therapeutic use
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Safety
MH  - Tuberculosis, Multidrug-Resistant/*drug therapy
PMC - PMC7977294
OTO - NOTNLM
OT  - Bedaquiline
OT  - China
OT  - Multidrug-resistant
OT  - Safety
OT  - Surveillance program
OT  - Tuberculosis
COIS- All authors declare that they have no competing interests.
EDAT- 2021/03/20 06:00
MHDA- 2021/08/19 06:00
PMCR- 2021/03/19
CRDT- 2021/03/19 05:53
PHST- 2020/12/08 00:00 [received]
PHST- 2021/03/05 00:00 [accepted]
PHST- 2021/03/19 05:53 [entrez]
PHST- 2021/03/20 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2021/03/19 00:00 [pmc-release]
AID - 10.1186/s40249-021-00819-2 [pii]
AID - 819 [pii]
AID - 10.1186/s40249-021-00819-2 [doi]
PST - epublish
SO  - Infect Dis Poverty. 2021 Mar 19;10(1):32. doi: 10.1186/s40249-021-00819-2.