Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis

Li, Jinmeng; Yang, Gaoyi; Cai, Qingshan; Wang, Yu; Xu, Yingying; Zhang, Ruoying; Lang, Yazhen; Cai, Xinjun

doi:10.1016/j.ijid.2021.07.038

Cited by 13 publications

(13 citation statements)

References 30 publications

(24 reference statements)

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“…However, most of them were gentle and tolerant. QTc prolongation was widely concerning when Bdq was applied, but generally, it is not serious [29][30][31][32]. In our study, although the cases number with a QTc ≥ 450 ms in Bdq group were more than that in non Bdq, no one withdrew Bdq as a result of QTc prolongation.…”

Section: Discussioncontrasting

confidence: 48%

Bedaquiline containing regimen showed excellent efficacy and safety for the treatment of pre-extensively drug-resistant tuberculosis

Fang

Liu

et al. 2022

Preprint

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Background Pre-extensively drug-resistant tuberculosis (Pre XDR-TB) was defined as resistant to fluroquinolones in Multidrug resistant tuberculosis (MDR TB), it had poorer outcomes than MDR TB in previous reports. In this study, we aimed to evaluate the efficacy and safety of the Bdq containing regimen for the treatment of Pre XDR-TB. Moreover, we tried to explore the optimal duration of Bdq and the total duration. Patients and methods : In this retrospective study, a total of 84 Pre XDR-TB from our hospital were enrolled and divided into Bdq group (46 cases) and non Bdq group (38 cases) according to their treatment regimen. Demographic, socioeconomic and clinical features were analyzed and compared between them in order to find out the factors associated with the outcomes. Then we compared the efficacy and safety between bedaquiline(Bdq) and non-bedaquiline containing regimens for treatment of Pre XDR-TB. Meanwhile, we analyze the outcomes among different Bdq duration and total regimen duration. P < 0.05 is significantly different, GraphPad prism 5.0 software package was used to process the data. Results 1.more male and younger cases as well as higher BMI appeared in Bdq group, In addition, medical care insurance types in Bdq group were superior comparing to those in non Bdq group( p < 0.05). More cases in Bdq group had taken Lzd for more than 1 month than non Bdq group before(p < 0.05). 2. The most frequent used drugs were Bdq(100%), Lzd(94%), Cs(82.61%), Cfz(73.91), etc in order for Bdq regimen. While the drugs were Lzd(94.74%), Cs(81.58%), Mfx(71.05%), Pza(71.05), Cfz(55.26%), etc in order for non Bdq regimen. 3. Favorable outcomes of Bdq group were significantly superior to non Bdq group( 89.13% vs 52.63%, p = 0.0002). While unfavorable outcomes of Bdq group was significantly lower than non Bdq group(10.87% vs 47.37%, p = 0.0002). 4. Both 2 patients who received Bdq for ≤ 12w(12w and 6w respectively) and a total duration < 9 months had unfavorable outcomes. While 2 of 4 patients (2/4, 50%) who receive Bdq for 18w-32w and a total duration < 9 months had also poor outcome. By contrast, all 22 cases who received Bdq for 18w-52w and a total duration 9–12 months had favorable outcomes. Another subgroup of 20 cases who received Bdq for 24w-52w and a total duration 13–24 month also got 100% favorable outcomes. In the longest duration subgroup ( Bdq for 36w total duration for 30–36 months), 1 in 3 patients obtained unfavorable outcome. 5. Safety assessment. The most common adverse effects are hyperuricemia, skin hyperpigmentation, QTc prolongation, peripheral neuritis, anemia etc in order. Most of the AEs are gentle and tolerant, SAEs which led to interruption of treatment or withdrawal of the suspected drug were rare, they mainly included severe Peripheral neuritis, Anemia, Liver injury, Anxiety or depression, etc. Conclusions Our study showed Bdq containing regimen achieved better outcomes for Pre XDR-TB compared with non Bdq (89.13% vs 52.63%, p < 0.01). AEs related to Bdq was mild, no case interrupted the treatment as a result of AEs associated with Bdq. Moreover, extension of Bdq duration was effective and tolerant. Generalization of Bdq is one of the vital measures to overcome this disease, but it needs to be managed standardly.

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Section: Discussioncontrasting

confidence: 48%

Bedaquiline containing regimen showed excellent efficacy and safety for the treatment of pre-extensively drug-resistant tuberculosis

Fang

Liu

et al. 2022

Preprint

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“…Compared with the standard regimen containing bedaquiline, QTc interval prolongation of more than 500 ms was found to be higher, between 6.2% and 25.6%. [37,38] A standard regimen includes fluoroquinolones (levofloxacin, moxifloxacin), clofazimine, and delamanid, potentially causing QT interval prolongation. Several studies have shown, although bedaquiline was associated with QTc prolongation, however, the grade of severity was low or middle, and no TdP or death-related cardiac arrhythmia was found.…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular potassium correction to the normal range shortens the QT interval. [39] Myelosuppression and neuropathy are considered the important causes of temporally or permanent discontinuation of linezolid in a regimen. Hematologic toxicity due to linezolid was associated with mitochondrial disruption.…”

Section: Discussionmentioning

confidence: 99%

Six Months of Bedaquiline-Pretomanid-Linezolid (BPaL) Regimen in Patients with Drug-Resistant Tuberculosis: A Narrative Review

Putra

Faizah

2023

JETROMI

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Background: Drug-resistant tuberculosis (DR-TB) is more difficult to treat with multiple therapies and a longer duration than drug-sensitive tuberculosis. Pre-XDR and XDR-TB are highly DR-TB with a lower success treatment than MDR-TB. Therapy for high DR-TB with fewer drugs and shorter treatment is required to increase the success of treatment. We comprehensively reviewed the risk factors for unfavorable outcomes (death, treatment failure, and loss of follow-up) related to all oral regimens containing bedaquiline and or delamanid in patients with MDR-TB. Method: This was a narrative review to summarize the role of the BPaL regimen to manage highly DR-TB patients. Results: The six months of BPaL regimen was reported to provide treatment success in two previous trials, Nix and Zenix TB. BPaL offers treatment success, especially in highly DR-TB compared to standard regimens containing bedaquiline. However, several adverse effects, such as myelosuppression, peripheral neuropathy, and optic neuritis were more common in BPaL regimens than in standard regimens. In addition, the incidence of QTc interval prolongation was lower in BPaL regimens compared with standard regimens. It is mandatory to monitor adverse effects associated with linezolid in the BPaL regimen and how to manage them. Conclusion: This review concludes that the BPaL regimen provides treatment success over six months of treatment. Health facilities should prepare for the implementation of BPaL to manage DR-TB patients.

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“…Indeed, numerous clinical studies confirm that the strong bactericidal and sterilizing activity of BDQ-containing regimen originally found in mouse models of TB ( 123 , 124 ). BDQ has demonstrated potent clinical activity against MDR-and XDR-TB complex strains ( 27 , 118 , 121 , 122 ). Importantly, BDQ-containing treatment regimens have showed improved outcomes rate over SLID-containing regimens for the treatment of patients with RR-/MDR-TB ( 120 ).…”

Section: Clinical Treatment Efficacy Of Bdqmentioning

confidence: 99%

“…Recently, the WHO suggested SLID be replaced in the standard STR with a BDQ-containing regimen. The recommended dose of BDQ is 400 mg orally once daily for 2 weeks followed by 200 mg orally three times weekly for 22 weeks and total duration of BDQ treatment was 24 weeks ( 117 , 118 , 120 ). Many studies have reported the use of BDQ favorable outcomes rates at week 24 of treatment exceeding 80% ( 15 , 117 ).…”

Section: Clinical Treatment Efficacy Of Bdqmentioning

confidence: 99%

Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis

Islam,

Alam,

Liu

et al. 2024

Front. Med.

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Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) Mtb strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against Mtb strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the Rv0678, pepQ, Rv1979c, and atpE genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against Mtb can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB.

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Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis

Cited by 13 publications

References 30 publications

Bedaquiline containing regimen showed excellent efficacy and safety for the treatment of pre-extensively drug-resistant tuberculosis

Bedaquiline containing regimen showed excellent efficacy and safety for the treatment of pre-extensively drug-resistant tuberculosis

Six Months of Bedaquiline-Pretomanid-Linezolid (BPaL) Regimen in Patients with Drug-Resistant Tuberculosis: A Narrative Review

Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis

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