Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis

Nguyen, Thi Van Anh; Cao, Thi Bich Tra; Akkerman, Onno W.; Tiberi, Simon; Vu, Dinh Hoa; Alffenaar, J W C

doi:10.1080/17512433.2016.1200462

Cited by 25 publications

(32 citation statements)

References 55 publications

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“…Therefore, the probability predicted by the Cardiac Risk Algorithm seems appropriate, and suggests that moxifloxacin could be classified as a middle risk compound. Bedaquiline was classified as TdP(−), consistent with the lack of TdP reported in bedaquiline clinical trials [ 42 ].…”

Section: Discussionmentioning

confidence: 78%

Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development

Polak

Romero

Berg

et al. 2018

J Pharmacokinet Pharmacodyn

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Cardiotoxicity is among the top drug safety concerns, and is of specific interest in tuberculosis, where this is a known or potential adverse event of current and emerging treatment regimens. As there is a need for a tool, beyond the QT interval, to quantify cardiotoxicity early in drug development, an empirical decision tree based classifier was developed to predict the risk of Torsades de pointes (TdP). The cardiac risk algorithm was developed using pseudo-electrocardiogram (ECG) outputs derived from cardiac myocyte electromechanical model simulations of increasing concentrations of 96 reference compounds which represented a range of clinical TdP risk. The algorithm correctly classified 89% of reference compounds with moderate sensitivity and high specificity (71 and 96%, respectively) as well as 10 out of 12 external validation compounds and the anti-TB drugs moxifloxacin and bedaquiline. The cardiac risk algorithm is suitable to help inform early drug development decisions in TB and will evolve with the addition of emerging data.Electronic supplementary materialThe online version of this article (10.1007/s10928-018-9580-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 78%

Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development

Polak

Romero

Berg

et al. 2018

J Pharmacokinet Pharmacodyn

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“…is delayed at the beginning, but accelerates later in therapy [21] . Despite the superior activity of kanamycin containing regimens at day 14, this more rapid early elimination of M. tuberculosis was not sustained as a long term-bactericidal effect, such that 3 patients on injectable containing but bedaquiline free regimen remained positive after 4 months of treatment.…”

Section: This Observation Concurs With Previous Reports That the Bactmentioning

confidence: 99%

Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate ofMycobacterium tuberculosisin patients with multidrug-resistant tuberculosis in Tanzania

Mbelele

Mpolya

Sauli

et al. 2020

Preprint

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BackgroundRifampin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has transitioned to injectable-free regimens. We tested whether M. tuberculosis (Mtb) elimination rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB antibiotic regimen.MethodsSerial sputa were collected from patients with RR/MDR- and drug-sensitive TB at day 0, 3, 7, 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable Mtb 16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL). Mtb elimination rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures.ResultsAmong 37 patients with a total of 296 serial sputa; 7 patients received rifampin/isoniazid/pyrazinamide/ethambutol (RHZE), 8 an all-oral bedaquiline-based regimen, 9 an injectable and bedaquiline-containing regimen, and 13 an injectable-containing but bedaquiline-free regimen. The overall mean daily Mtb elimination was −0.24 [95% Confidence-Interval (CI); −0.39 to −0.08)] log10 eCFU/mL, and it varied with treatment-regimen (p < 0.001). Compared to the adjusted Mtb elimination of −0.17 (95% CI; −0.23 to −0.12) for the injectable-containing but bedaquiline-free reference regimen, the elimination rates were −0.62 (95% CI; −1.05 to −0.20) log10 eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), −0.35 (95% CI; −0.65 to −0.13) log10 eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and −0.29 (95% CI; −0.78 to +0.22) log10 eCFU/mL for RHZE (p = 0.332)ConclusionTB-MBLA distinguished Mtb elimination rates in sputa from patients receiving different treatment regimens, suggesting a reliable monitoring tool for RR/MDR-TB, that does not require mycobacterial culture.

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“…Atualmente, a OMS recomenda o uso da bedaquilina para o tratamento da TB-MDR/XDR, mas só quando combinada com outros três fármacos eficientes. (SILVA et al, 2018;SILVA et al, 2019;NGUYEN et al, 2016).…”

Section: Perspectivas E Avanços No Desenvolvimento De Fármacos Contraunclassified

“…Aproximadamente 11,4% dos pacientes que administraram o medicamento vieram a óbito durante os ensaios clínicos, quando comparado a 2,5% dos que fizeram uso de placebos. (SILVA et al, 2019;NGUYEN et al, 2016).…”

Section: Perspectivas E Avanços No Desenvolvimento De Fármacos Contraunclassified

A Importância Do Profissional Farmacêutico No Processo De Cura Da Tuberculose/the Importance of Pharmaceutical Professionals in the Tuberculosis Healing Process

Nicoletti¹,

Antunes²,

Gurgel³

et al. 2020

BJD

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Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis

Cited by 25 publications

References 55 publications

Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development

Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development

Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate ofMycobacterium tuberculosisin patients with multidrug-resistant tuberculosis in Tanzania

A Importância Do Profissional Farmacêutico No Processo De Cura Da Tuberculose/the Importance of Pharmaceutical Professionals in the Tuberculosis Healing Process

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