QTc and anti-tuberculosis drugs: a perfect storm or a tempest in a teacup? Review of evidence and a risk assessment

Monedero-Recuero, Ignacio; Marrupe, Lorenzo Hernando; Sánchez-Montalvà, Adrián; Cox, Vivian; Tommasi, Marcela; Furin, Jennifer; Chiang, Cheng-Wen; Quelapio, Mamel; Koura, Kobto Ghislain; Trébucq, A; Padanilam, Xavier; Dravniece, Gunta; Piubello, Alberto

doi:10.5588/ijtld.18.0423

Cited by 27 publications

(27 citation statements)

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“…QT prolongation was well documented in the STREAM trial and was not significantly more frequent with the use of the STR than with the long treatment (11.0% vs. 6.4%, p = 0.14) [13]. QT prolongation leading to severe clinical disorders, such as torsade de pointes is rare [28]; none was documented in the nine-country or the STREAM studies.…”

Section: Adverse Events (Aes)mentioning

confidence: 92%

“…The QT interval on the ECG represents the electrical depolarization-repolarization of myocardial cells that leads to ventricular contractions. Moxifloxacin and clofazimine are suspected of increasing the risk of QT prolongation [28]. QT prolongation was well documented in the STREAM trial and was not significantly more frequent with the use of the STR than with the long treatment (11.0% vs. 6.4%, p = 0.14) [13].…”

Section: Adverse Events (Aes)mentioning

confidence: 95%

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Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Trébucq

Decroo

Deun

et al. 2019

JCM

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About ten years ago, the first results of the so-called “Bangladesh regimen”, a short regimen lasting nine months instead of 20 months, revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment. Similar short regimens were studied in different settings, relying for their efficacy on a later generation fluoroquinolone, either gatifloxacin, moxifloxacin, or levofloxacin. We review the published material on short MDR-TB regimens, describe their different compositions, their results in national tuberculosis programs in middle- and low-income countries, the risk of acquiring resistance to fluoroquinolone, and the occurrence of adverse events. With over 80% success, the regimen performs much better than longer regimens (usually around 50%). Monitoring of adverse events allows adapting its composition to prevent severe adverse events such as deafness. We discuss the current applicability and usefulness of the short injectable-containing regimen given the 2019 recommendation of the World Health Organization (WHO) for a new long all-oral regimen. We conclude that the most effective fluoroquinolone is gatifloxacin, currently not listed as an essential medicine by WHO. It is a priority to restore its status as an essential medicine.

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Section: Adverse Events (Aes)mentioning

confidence: 92%

Section: Adverse Events (Aes)mentioning

confidence: 95%

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Trébucq

Decroo

Deun

et al. 2019

JCM

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“…In particular, bedaquiline has recently emerged as a key drug to be included in regimens despite the fact that it received temporary approval after only a phase 2B clinical trial and without full information on its efficacy and potential toxicity [1,23]. Fortunately, despite initial concerns on possible cardiac toxicity (QT interval prolongation on electrocardiogram), recent data show that such toxicity is limited in severity and frequency, and is generally reversible [29,30]. Nevertheless, particular attention in monitoring QT is necessary when bedaquiline is given with other drugs with a potential to prolong the QT interval, i.e.…”

Section: Dots-plusmentioning

confidence: 99%

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

2019

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Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20–24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9–10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.

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“…The traditional longer regimens are usually for 18–24 months, but shorter regimens of 9–12 months are now recommended, provided resistance to fluoroquinolones and second-line injectable agents has been excluded or is considered highly unlikely. Well conducted operational research has been valuable to date [43,44] and will be needed in the future to determine (i) what are the most suitable short regimens for local context; (ii) how best to replace injectable agents with oral drugs, such as bedaquiline, delamanid and linezolid; and (iii) how in resource-limited settings, NTPs can implement and read the electrocardiograms deemed necessary to monitor prolonged QT intervals that may occur with high dose moxifloxacin, an essential drug in the shorter MDR-TB regimens [45].…”

Section: Operational Research To Improve Tb Programme Performancementioning

confidence: 99%

How Can Operational Research Help to Eliminate Tuberculosis in the Asia Pacific Region?

et al. 2019

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Broad multi-sectoral action is required to end the tuberculosis (TB) epidemic by 2030 and this includes National TB Programmes (NTPs) fully delivering on quality-assured diagnostic, treatment and preventive services. Large implementation gaps currently exist in the delivery of these services, which can be addressed and closed through the discipline of operational research. This paper outlines the TB disease burden and disease-control programme implementation gaps in the Asia-Pacific region; discusses the key priority areas in diagnosis, treatment and prevention where operational research can be used to make a difference; and finally provides guidance about how best to embed operational research within a TB programme setting. Achieving internationally agreed milestones and targets for case finding and treatment requires the NTP to be streamlined and efficient in the delivery of its services, and operational research provides the necessary evidence-based knowledge and support to allow this to happen.

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QTc and anti-tuberculosis drugs: a perfect storm or a tempest in a teacup? Review of evidence and a risk assessment

Cited by 27 publications

References 0 publications

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

How Can Operational Research Help to Eliminate Tuberculosis in the Asia Pacific Region?

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