Insignificant difference in culture conversion between bedaquiline-containing and bedaquiline-free all-oral short regimens for multidrug-resistant tuberculosis

Fu, Liang; Weng, Taoping; Sun, Feng; Zhang, Peize; Li, Hui; Li, Yang; Yang, Qianting; Cai, Yuchen; Zhang, Xilin; Hong, Liang; Chen, Xinchun; Wang, Zhaoqing; Liu, Lei; Zhang, Wenhong; Deng, Guofang

doi:10.1016/j.ijid.2021.08.055

Cited by 19 publications

(24 citation statements)

References 28 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pyrazinamide and linezolid were two-most ADR inducing drugs. 91 Based on the existing studies, it can be concluded that delamanid, bedaquiline, clofazimine, pretomanid, fluoroquinolone, and linezolid are novel and repurposed drugs that effective and well tolerated. These agents are promising and may improve QoL and adherence of DR TB patients.…”

Section: Discussionmentioning

confidence: 99%

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy

Ausi¹,

Santoso²,

Sunjaya³

et al. 2021

PPA

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy

Ausi¹,

Santoso²,

Sunjaya³

et al. 2021

PPA

View full text Add to dashboard Cite

“…However, in one study, patients described skin changes as “stigmatizing” ( Ramu and Iyer, 1976 ) and case reports of depression have been linked to skin discolouration ( Tang et al, 2015 ), illustrating the adverse impact it may have on patients’ quality of life. In a recent trial conducted in China evaluating alternative short all-oral regimens that factored in drug affordability and patients’ willingness to tolerate skin discolouration, more than 10% of patients opted out of clofazimine treatment when given the option ( Fu et al, 2021 ). These reports suggest that clofazimine-induced skin discoloration may significantly impact on quality of life and psychological wellbeing in some patients or populations and may ultimately affect willingness to adhere to treatment, if ignored.…”

Section: Introductionmentioning

confidence: 99%

Clofazimine for the treatment of tuberculosis

et al. 2023

View full text Add to dashboard Cite

Shorter (6–9 months), fully oral regimens containing new and repurposed drugs are now the first-choice option for the treatment of drug-resistant tuberculosis (DR-TB). Clofazimine, long used in the treatment of leprosy, is one such repurposed drug that has become a cornerstone of DR-TB treatment and ongoing trials are exploring novel, shorter clofazimine-containing regimens for drug-resistant as well as drug-susceptible tuberculosis. Clofazimine’s repurposing was informed by evidence of potent activity against DR-TB strains in vitro and in mice and a treatment-shortening effect in DR-TB patients as part of a multidrug regimen. Clofazimine entered clinical use in the 1950s without the rigorous safety and pharmacokinetic evaluation which is part of modern drug development and current dosing is not evidence-based. Recent studies have begun to characterize clofazimine’s exposure-response relationship for safety and efficacy in populations with TB. Despite being better tolerated than some other second-line TB drugs, the extent and impact of adverse effects including skin discolouration and cardiotoxicity are not well understood and together with emergent resistance, may undermine clofazimine use in DR-TB programmes. Furthermore, clofazimine’s precise mechanism of action is not well established, as is the genetic basis of clofazimine resistance. In this narrative review, we present an overview of the evidence base underpinning the use and limitations of clofazimine as an antituberculosis drug and discuss advances in the understanding of clofazimine pharmacokinetics, toxicity, and resistance. The unusual pharmacokinetic properties of clofazimine and how these relate to its putative mechanism of action, antituberculosis activity, dosing considerations and adverse effects are highlighted. Finally, we discuss the development of novel riminophenazine analogues as antituberculosis drugs.

show abstract

“…Some studies had demonstrated that regimen containing Bdq and Lzd was able to achieve the similar favorable outcomes between MDR PTB and PRE XDR-TB. But these studies lacked data of long term outcome [10,[17][18][19]. Meanwhile, a control regimen without Bdq was absent.…”

Section: Discussionmentioning

confidence: 99%

“…Positive liquid isolates were then transferred to the Roche solid culture inoculation for conventional DST, the absolute concentration method which covered 10 drugs was performed before December 2019. Thereafter the minimum inhibitory concentration (MIC) method (Sensititre® MYCOTB; Thermo Scienti c, USA) was also applied at the laboratory of Shenzhen Third People's Hospital [10].…”

Section: Methodsmentioning

confidence: 99%

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

Fang

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Insignificant difference in culture conversion between bedaquiline-containing and bedaquiline-free all-oral short regimens for multidrug-resistant tuberculosis

Cited by 19 publications

References 28 publications

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy

Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy

Clofazimine for the treatment of tuberculosis

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

Contact Info

Product

Resources

About