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Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several reports highlighted the risk of infection and disease in pregnant women and neonates. To assess the risk of clinical complications in pregnant women and neonates infected with SARS-CoV-2 carrying out a systematic review and meta-analysis of observational studies. Data sources: Search of the scientific evidence was performed using the engines PubMed and Scopus, including articles published from December 2019 to 15 April 2020. Study eligibility criteria: Only observational studies focused on the assessment of clinical outcomes associated with pregnancy in COVID-19 women were selected. Study appraisal and synthesis methods: The first screening was based on the assessment of titles and abstracts, followed by the evaluation of full-texts. Qualitative variables were summarized with frequencies, whereas quantitative variables with central and variability indicators depending on their parametric distribution. Forest plots were used to describe point estimates and in-between studies variability. Study quality assessment was performed. Results: Thirteen studies were selected. All of them were carried out in China. The mean (SD) age and gestational age of pregnant women were 30.3 (1.5) years and 35.9 (2.9) weeks, respectively. The mean (SD) duration from the first symptoms to the hospital admission and to labour were 5.5 (2.0) and 9.5 (8.7) days, respectively. Patients mainly complained of fever and cough (pooled (95 % CI) proportions were 76.0 % (57.0 %-90.0 %) and 38.0 (28.0 %-47.0 %), respectively). Several antibiotics, antivirals, and corticosteroids were prescribed in different combinations. The pooled prevalence of maternal complications and of caesarean section were 45.0 % (95 % CI: 24.0 %-67.0 %) and 88.0 % (95 %CI: 82.0 %-94.0 %). A proportion of pregnant women less than 20 % were admitted to ICU. The pooled proportion of preterm infants was 23.0 % (95 %CI: 11.0 %-39.0 %). The most frequent neonatal complications were pneumonia and respiratory distress syndrome. The pooled percentage of infected neonates was 6.0 % (95 %CI: 2.0 %-12.0 %). Conclusions: The present study suggests a high rate of maternal and neonatal complications in infected individuals. However, the current scientific evidence highlights a low risk of neonatal infection. Multicentre, cohort studies are needed to better elucidate the role of SARS-CoV-2 during pregnancy.

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The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.