Effects of bedaquiline: A Synthesis of Findings from 8 Studies

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Original Abstract of the Article

Main Research Findings

Bedaquiline is a promising new anti-tuberculosis drug, but it can interact with other medications, potentially affecting its effectiveness and causing side effects. 8 、 6 A study examining the interaction between bedaquiline and efavirenz, a commonly used antiretroviral, found that efavirenz reduced bedaquiline levels by 52%. 8 Another study investigating the effect of rifamycins on bedaquiline metabolism found that rifabutin increased bedaquiline metabolite levels, while rifampin decreased them. 6 These findings suggest that careful dose adjustments might be needed when bedaquiline is used with these medications. 8 Bedaquiline can also prolong the QTc interval, which could lead to heart rhythm problems. 5 Further, the combination of bedaquiline with other drugs that affect the QT interval, such as fluoroquinolones and clofazimine, significantly increases the risk of QT prolongation. 2 Overall, these studies indicate that while bedaquiline is a valuable treatment option for multidrug-resistant tuberculosis, its use should be carefully monitored, especially when combined with other medications. 4

Benefits and Risks

Benefit Summary

Bedaquiline is a powerful anti-tuberculosis drug, especially effective against multidrug-resistant tuberculosis. 4 It has demonstrated bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. 3 Studies suggest that bedaquiline might even be effective against non-culturable Mycobacterium abscessus. 1 Bedaquiline's mechanism of action, inhibiting energy metabolism in the bacteria, makes it a promising drug for treating tuberculosis. 7 Overall, bedaquiline is a significant advancement in the fight against tuberculosis, especially against drug-resistant strains. 4

Risk Summary

Bedaquiline is associated with risks, including potential interactions with other medications, possible cardiac side effects, and potential for drug-induced toxicity. 8 、 6 、 2 Bedaquiline can extend the QTc interval, potentially causing heart rhythm issues. 5 、 2 The risk of QT prolongation is heightened when bedaquiline is combined with other drugs affecting the QT interval. 2 While bedaquiline is a valuable treatment option for multidrug-resistant tuberculosis, it's essential to be aware of these risks and use it with caution and close monitoring. 4

Comparison between Studies

Commonalities in Studies

All studies examined the effectiveness of bedaquiline in treating tuberculosis. 8 、 5 、 4 、 3 、 2 、 1 、 7 、 6 They consistently highlighted its potential to interact with other medications, impacting its efficacy and leading to adverse effects. 8 、 5 、 2 、 6 The studies also pointed out bedaquiline's role in extending the QTc interval and the need for careful monitoring when combined with other medications. 5 、 2 Despite its effectiveness, the studies agreed that further research is crucial to fully understand bedaquiline's side effects and risks. 8 、 5 、 2 、 4 、 6

Differences in Studies

The studies differed in their focus, methodology, and subjects. 8 、 5 、 2 、 4 、 3 、 1 、 7 、 6 While all studies emphasized bedaquiline's potential as a treatment option for tuberculosis, they also recognized the need for further research to better understand its side effects, risks, and optimal dosage. 8 、 5 、 2 、 4 、 6

Consistency and Contradictions in Results

The studies consistently demonstrated bedaquiline's effectiveness in treating tuberculosis, but some contradictions exist regarding its side effects and risks. 8 、 5 、 2 、 4 While some studies highlighted the potential for QT interval prolongation with bedaquiline use, others didn't confirm this risk consistently. 5 、 2 The interaction of bedaquiline with other medications was also investigated, but the findings weren't entirely consistent across studies. 8 、 6 The need for further research to fully understand bedaquiline's side effects and risks is emphasized by these discrepancies. 8 、 5 、 2 、 4 、 6

Cautions for Practical Applications

Bedaquiline is a valuable treatment option for multidrug-resistant tuberculosis, but its use should be approached with caution due to potential cardiac side effects, interactions with other medications, and possible toxicity. 8 、 5 、 2 、 6 It's crucial to be aware of these risks and discuss them with your doctor before starting treatment. 8 、 5 、 2 、 4 Close monitoring during treatment is essential to manage potential side effects and ensure the best possible outcome. 8 、 5 、 2 、 4

Limitations of Current Research

The research on bedaquiline's effects is ongoing, and the current studies have limitations. 8 、 5 、 2 、 4 、 6 Most studies have a limited number of participants, which restricts the generalizability of their findings. 8 、 5 、 2 、 4 、 3 、 1 、 7 、 6 Furthermore, the duration of most studies is relatively short, leaving the long-term effects of bedaquiline unclear. 8 、 5 、 2 、 4 、 6

Future Research Directions

Further research is necessary to better understand bedaquiline's side effects, risks, and optimal dosage. 8 、 5 、 2 、 4 、 6 In particular, a detailed investigation of bedaquiline's interaction with other medications is crucial. 8 、 6 Long-term studies are also needed to assess bedaquiline's long-term impact. 8 、 5 、 2 、 4 、 6

Conclusion

Bedaquiline is a promising drug for treating tuberculosis, especially multidrug-resistant strains, but it carries risks such as interactions with other medications, potential cardiac side effects, and the possibility of toxicity. 8 、 5 、 2 、 4 It's crucial to discuss these risks with your doctor before starting treatment with bedaquiline. 8 、 5 、 2 、 4 Continued research is essential to fully understand bedaquiline's long-term effects and establish optimal dosage and safety guidelines. 8 、 5 、 2 、 4 、 6

Literature analysis of 8 papers
Positive Content
8
Neutral Content
0
Negative Content
0
Article Type
2
0
0
0
8
3.

Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant <i>Mycobacterium tuberculosis</i> Strains.

Author: LyuXia-Li, LinTing-Ting, GaoJing-Tao, JiaHong-Yan, ZhuChuan-Zhi, LiZi-Hui, DongJing, SunQi, ShuWei, WangSai-Sai, PanLi-Ping, HuangHai-Rong, ZhangZong-De, LiQi

TB treatment

This study explored the bactericidal effects of bedaquiline (Bdq) against multidrug-resistant Mycobacterium tuberculosis strains (MDR-MTBs) and their impact on MDR-MTBs-infected macrophages. The study found that Bdq exerted bactericidal effects against MDR-MTBs and influenced the immune response of macrophages.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial.

Author: DooleyKelly E, RosenkranzSusan L, ConradieFrancesca, MoranLaura, HafnerRichard, von Groote-BidlingmaierFlorian, LamaJavier R, ShenjeJustin, De Los RiosJorge, CominsKyla, MorganrothJoel, DiaconAndreas H, CramerYoninah S, DonahueKathleen, MaartensGary,

TB treatment
QTc prolongation

This study aims to investigate the effects of bedaquiline and delamanid, two new drugs for tuberculosis treatment, on the QTc interval over six months of multidrug treatment in patients with multidrug-resistant or rifampicin-resistant tuberculosis. Both drugs can prolong the QTc interval, and the study will assess their cardiac safety and microbiological activity when co-administered.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Effects of Rifamycin Coadministration on Bedaquiline Desmethylation in Healthy Adult Volunteers.

Author: HealanAmanda M, SalataRobert A, GriffissJ McLeod, ProskinHoward M, O'RiordanMary Ann, GrayWesley A, BlumerJeffrey L

MDR TB treatment
Cytotoxicity
Phospholipidosis

Rifabutin, a drug used to treat drug-resistant tuberculosis (TB), was found to increase the exposure to bedaquiline metabolites, which are cytotoxic and can induce phospholipidosis, highlighting the need for careful monitoring when these drugs are coadministered.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

7.

Ionophoric effects of the antitubercular drug bedaquiline.

Author: HardsKiel, McMillanDuncan G G, Schurig-BriccioLici A, GennisRobert B, LillHolger, BaldDirk, CookGregory M

Effective therapeutics

Bedaquiline (BDQ), an antitubercular drug, was found to inhibit ATP synthesis in bacteria by functioning as a H+/K+ ionophore. This uncoupling effect may be a new mechanism for developing effective therapeutics.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients coinfected with HIV and tuberculosis.

Author: SvenssonElin M, AweekaFrancesca, ParkJeong-Gun, MarzanFlorence, DooleyKelly E, KarlssonMats O

Improved TB treatment
Drug interaction

This study developed a pharmacokinetic model to predict the interaction between bedaquiline (BDQ) and efavirenz (EFV) in patients with tuberculosis and HIV infection. The model predicted that EFV would significantly reduce BDQ exposure. Simulations suggested that adjusting the standard BDQ regimen during EFV coadministration could mitigate this interaction effect. Clinical trials are needed to evaluate these adjusted regimens and ensure appropriate dosing.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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