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

Plant Milking Technology—An Innovative and Sustainable Process to Produce Highly Active Extracts from Plant Roots

We have used an original technology (Plant Milking Technology) based on aeroponic cultivation of plants associated with the gentle recovery of active ingredients from roots. Extraction of bioactive molecules was achieved by soaking the roots, still attached to the living plants, into a nontoxic solvent for a 2 h period. This nondestructive recovery process allows using the same root biomass for successive harvesting dates, in a recyclable way. We have applied this technology to Morus alba L. (mulberry tree), an emblematic tree of the Traditional Chinese Medicine (TCM). Trees were aeroponically grown in large-scale devices (100 m2) and were submitted to nitrogen deprivation to increase the content in active molecules (prenylated flavonoids). The Plant Milking technology applied to Morus alba L. allowed to produce an extract enriched in prenylated compounds (18-fold increase when compared to commercial root extract). Prenylated flavonoids (moracenin A and B, kuwanon C, wittiorumin F, morusin) presented a high affinity for the aged-associated collagenase enzyme, which was confirmed by activity inhibition. In accordance, M. alba extract presents efficient properties to regulate the skin matrisome, which is critical during skin aging. The benefits have been especially confirmed in vivo on wrinkle reduction, in a clinical study that involved aged women. Plant Milking technology is an optimal solution to produce active ingredients from plant roots, including trees, that meet both customer expectations around sustainability, as well as the need for an efficient production system for biotechnologists

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