Safety and efficacy of exposure to bedaquiline-delamanid in multidrug-resistant tuberculosis : A case series from France and Latvia

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Revised Definitions of Tuberculosis Resistance and Treatment Outcomes, France, 2006–2019

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Is bedaquiline as effective as fluoroquinolones in the treatment of multidrug-resistant tuberculosis?

The MDR-TB Management Group of the French National Reference Center for Mycobacteria and the Physicians of the French MDR-TB CohortInternational audienceBedaquiline (Bdq) is approved for the treatment of multidrug-resistant (MDR) tuberculosis (TB). In a phase IIb trial, Bdq allowed a significant reduction in time to culture conversion and improved outcome in MDR-TB patients [1, 2]. Preliminary reports of Bdq compassionate use have shown promising results [3–5]. However, in an early bactericidal activity (EBA) study, the association of moxifloxacin (Mfx) with PA-824 and pyrazinamide showed better activity than Bdq-based associations [6]. In addition, resistance to fluoroquinolones (Fq) has been associated with poorer outcome in MDR-TB before Bdq use [7]. These data reinforce the pivotal role of Fq. Comparing Bdq to Fq in interventional studies is challenging. Indeed, the paucity of drugs available for MDR-TB treatment, and the need for combination therapy, often impose the need to use all available drugs

Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis

for the French MDR-TB Management Group9International audienceBedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort

Limited Benefit of the New Shorter Multidrug-Resistant Tuberculosis Regimen in Europe [Letters to the Editor]

European MDR-TB database collaboration: Sofia Alexandru, Neus Altet, Korkut Avsar, Didi Bang, Raisa Barbuta, Graham Bothamley, Ana Ciobanu, Valeriu Crudu, Manfred Danilovits, Martin Dedicoat, Raquel Duarte, Mathilde Fréchet-Jachym, Gina Gualano, Lorenzo Guglielmetti, Gunar Günther, Jan Heyckendorf, Barbara Kalsdorf, Heinke Kunst, Christoph Lange, Wiel de Lange, Damien Le Dû, Vaira Leimane, Frank van Leth, Rita Macedo, Cecile Magis-Escurra, Anne-Marie McLaughlin, Inge Muylle, Ioana D Olaru, Olena Oliveira, Veronika Polcová, Emanuele Pontali, Cristina Popa, Jérôme Robert, Rudolf Rumetshofer, Alena Skrahina, Varvara Solodovnikova, Victor Spinu, Simon Tiberi, Nicolas Veziris, Piret ViikleppEuropean MDR-TB database collaboration: Rita Macedo, INSA, Portugal[Letters to the Editor]Extract: The emergence of multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance to at least rifampicin and isoniazid, threatens global TB control. The number of patients notified with MDR-TB worldwide has increased by 261% from 2009 to 2014, and more than one-third of these patients currently live in the European Region of the World Health Organization (WHO). Management of patients with MDR-TB is challenging owing to the long duration of therapy required to achieve a relapse-free cure, complex drug regimens, frequent drug-related adverse events, high costs, suboptimal adherence, and overall low cure rates. [...]info:eu-repo/semantics/publishedVersio

Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis

Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%–81.9%), and the treatment success rate was 65.8% (95% CI 59.9%–71.3%). Death rate was 11.7% (95% CI 7.0%–19.1%). Up to 91.1% (95% CI 82.2%–95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%–23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low