Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium.

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis.

SETTING: Bedaquiline (BDQ) has been approved for the treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB). For many patients treatment is prolonged beyond the recommended 6 months. The long-term pharmacokinetics of BDQ have yet to be elucidated. OBJECTIVE: To evaluate plasma concentrations of BDQ during treatment and its elimination after treatment discontinuation. DESIGN: This was a retrospective study conducted in two units in France that provide treatment for MDR/XDR-TB. Sociodemographic, clinical, biological and therapeutic parameters were collected from patients currently or formerly treated with BDQ. Plasma concentrations of BDQ and its active M2 (N-desmethyl) metabolite were determined using ultra-performance liquid chromatography with tandem mass spectrometry. RESULTS: Thirteen patients were recruited (35 samples): 10 (31 samples) during BDQ treatment and 3 (4 samples) after BDQ discontinuation. The median duration of treatment with BDQ was 11 months (interquartile range [IQR] 8-14). During treatment, the median plasma BDQ concentrations and M2 were respectively 1264 ng/ml (IQR 910-2244) and 252 ng/ml (IQR 134-290). In one patient, BDQ was detected in the plasma 200 days after treatment discontinuation (528 ng/ml). CONCLUSION: BDQ and M2 plasma concentrations were consistent with good drug efficacy/safety profiles, suggesting good treatment adherence with no relevant drug interactions. The long-term plasma detectability of BDQ after treatment discontinuation may raise the spectre of the emergence of resistance.

[Adjuvant surgical resection for multidrug-resistant tuberculosis: A review]. / Chirurgie et tuberculose multi/ultrarésistante : une revue de la littérature réhabilite une intervention adjuvante à l'antibiothérapie chez des patients sélectionnés.

INTRODUCTION: The frequency of multi and extensively drug resistant pulmonary tuberculosis (MDR/XDR-TB) is increasing worldwide, with major issues related to treatment modalities and outcome. In this setting, the exact benefits associated with surgical resection are still unknown. METHODS: We performed a literature review to determine the indications, morbidity, mortality and bacteriological success associated with the surgical management of MDR/XDR-TB patients. RESULTS: Altogether, 177 publications dealing with surgical resection and MDR/XDR-TB have been analyzed, including 35 surgical series and 24 cohort studies summarized in one meta-analysis. The surgical series reported success rates from 47% to 100%, complication rates from 0 to 29%, and mortality rates from 0 to 8%. The published meta-analysis reported a statistically significant association between surgical resection and treatment success (OR 2.24, IC95% 1.68-2.97). However, all these studies were associated with selection bias. International consensual guidelines included a multidisciplinary assessment in a reference centre, a personalized and prolonged antibiotic treatment and a medico-surgical discussion on a case-to-case basis. PERSPECTIVES: These guidelines are now applied for the management of patients with MDR/XDR-TB in our centre. Further studies are required to avoid further increase in the burden of MDR/XDR-TB and to establish the optimal timing of medical and surgical treatments.

A surge of MDR and XDR tuberculosis in France among patients born in the Former Soviet Union.

A marked increase in the number of multidrug-resistant (MDR) tuberculosis (TB) cases entirely related to patients born in the Former Soviet Union was observed in France in the last two years. Very few cases were clustered, suggesting it is a consequence of recent immigration of patients already infected in their country of origin. This major increase challenges the existing structures for management of MDR and extensively drug-resistant TB (XDR-TB).