Conclusion: Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.

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Amidst the COVID-19 pandemic, there is a need for further research on its manifestation in pregnant women, since they are particularly prone to respiratory pathogens, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to physiological changes during pregnancy. Its effects on infants born to mothers with COVID-19 are also not well-studied, and more evidence is needed on vertical transmission of the disease from mother to infant and on the transmission of IgG/IgM antibodies between mother and infant. We aim to systematically review and evaluate the effects of COVID-19 among SARS-CoV-2-positive pregnant women in late pregnancy and neonates with SARS-CoV-2-positive pregnant mothers using blood assays to find indicators of maternal and neonatal complications. We searched for original published articles in Google Scholar, Medline (PubMed), and Embase databases to identify articles in the English language from December 2019 to July 20, 2020. Duplicate entries were searched by their titles, authors, date of publication, and Digital Object Identifier. The selected studies were included based on patient pregnancy on admission, pregnant mothers with laboratory-confirmed COVID-19 virus, maternal/neonatal complications, and blood test results. We excluded duplicate studies, articles where full text was not available, other languages than English, opinions, and perspectives. The meta-analysis using the Generalized Linear Mixed model was conducted using the “meta” and “metaprop” packages in R code. Of the 1,642 studies assessed for eligibility, 29 studies (375 mothers and neonates) were included. Preterm birth rate was 34.2%, and cesarean section rate was 82.7%. Maternal laboratory findings found elevated neutrophils (71.4%; 95% CI: 38.5–90.9), elevated CRP (67.7%; 95%: 50.6–81.1), and low hemoglobin (57.3%; 95% CI: 26.0–87.8). We found platelet count, lactate dehydrogenase, and procalcitonin to be less strongly correlated with preterm birth than between high neutrophil counts (P = 0.0007), low hemoglobin (P = 0.0188), and risk of preterm birth. There is little evidence for vertical transmission. Elevated procalcitonin levels (23.2%; 95% CI: 8.4–49.8) are observed in infants born to mothers with COVID-19, which could indicate risk for neonatal sepsis. These infants may gain passive immunity to COVID-19 through antibody transfer via placenta. These results can guide current obstetrical care during the current SARS-CoV-2 pandemic.

Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Introduction Diabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM. Methods The study of patients with MDR/XDR-TB with or without DM (enrolled February 2018–September 2019, 21 Chinese hospitals) was supervised by the New Drug Introduction and Protection Program (NDIP). Of 640 patients with MDR/XDR-TB receiving BDQ-containing anti-TB treatments, two propensity score-matched groups (107 DM/107 non-DM) were compared for cumulative culture conversion rate, time to culture conversion, adverse events, and corrected QT interval. Results Body mass index was higher in patients with DM than patients without DM (23.29 ± 3.9 vs. 20.5 ± 3.6, P < 0.001); lung cavity prevalence (86.9% vs. 72.9%, P = 0.037) was also higher in patients with DM; the non-DM group had higher hepatitis prevalence (29.0% vs. 15.9%, P = 0.022). No significant intergroup differences were found for sputum culture conversion rate at week 8 (80.0% vs. 81.4%, P = 0.884), at week 24 (95.6% vs. 98.2%, P = 0.629), or for median time to sputum culture conversion [56 days (IQR 28–63) vs. 56 days (IQR 28–84) ( P = 0.687)]. Favorable post-24-week treatment outcomes were presented by 90.7% and 93.5% in the DM group and non-DM group, respectively, without significant intergroup differences ( P = 0.448). The DM adverse event rate exceeded non-DM rate (77.6% vs. 64.5%, P = 0.035). Conclusion Despite some differences in baseline characteristics, Chinese patients with MDR/XDR-TB with or without DM had similar sputum culture conversion rates and favorable treatment outcomes post-24-week BDQ-containing anti-TB treatment. Low BMI but not DM is risk factor associated with unfavorable outcome of patients with MDR/XDR-TB. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00396-9.