Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

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.

[Effects of ZnO Nanoparticles, ZnSO4 and Arbuscular Mycorrhizal Fungus on the Growth of Maize].

As one of the most widely used metal-based nanoparticles (NPs), ZnO NPs have been shown to be toxic to organisms. Arbuscular mycorrhizal (AM) fungi can improve mineral nutrition and increase the resistance of host plants. However, little is known on the interaction between ZnO NPs and other Zn pollutants, as well as the effect of AM fungi on their biological effects. The present greenhouse pot culture experiment studied the effects of inoculation with or without AM fungus Funneliformis mosseae BEG 167 on the growth of maize in soil supplemented with ZnO NPs and ZnSO4 (500 mg · kg⁻¹) seperately or in combination. The results showed that ZnO NPs inhibited mycorrhizal colonization and the growth of maize plants, showing similar phytotoxicity and effects to ZnSO4at the same concentration (500 mg · kg⁻¹). Compared with the nonmycorrhizal controls, AM fungal inoculation decreased Zn concentrations or uptake in maize plants, and showed a better growth-promoting effect in the combination treatment. Our results showed for the first time that there was a complex interaction in their biological toxicity between ZnO NPs and ZnSO4, while AM fungal inoculation exhibited a protective effect under combined pollution of ZnO NPs and ZnSO4.

[Characteristics of ammonium N and nitrate N accumulation in dryland soil in relation with wheat yield].

A total of eleven field trials in Yongshou, Shaanxi Province and seven in Luoyang, Henan Province were conducted with two treatments (without N as control and with 150 kg N x hm(-2) addition). The wheat biomass and seed yield were determined, and so were the nitrate and ammonium N concentrations in five layers (0-20, 20-40, 40-60, 60-80, 80-100 cm) at each trial site. Results showed that soil ammonium concentrations in the two provinces were very low while nitrate N concentrations were relatively high. Soil nitrate N occupied 91% of the total mineral N, and exhibited the same trend as the total mineral N in reflecting soil N supplying capacity. Without N application, the cumulative nitrate N amounts in the 0-40, 0-60, 0-80 and 0-100 cm layers in Yongshou were significantly correlated with wheat biomass and seed yield while no such correlation existed in Luoyang. With N addition, the relations of cumulative nitrate N of the different layers to wheat biomass and yield were greatly declined in Yongshou whereas those of Luoyang were changed to be negative. The yield increases were significantly correlated with the amount of nitrate N accumulated in the 0-80 and 0-100 cm layers of the two sites under N addition. Wheat mainly depended on nitrate N from the 0-20 cm layer at seedling stage, 0-40 cm at reviving, and 0-60 cm at elongation stages, and could utilize 0-100 cm nitrate N at maturity. After wheat harvest, the concentration of ammonium N was not significantly different from the initial value while that of nitrate N greatly decreased.

[Contribution of wheat rhizosphere respiration to soil respiration under elevated atmospheric CO2 and nitrogen application].

With the support of free-air carbon dioxide enrichment (FACE) system and by using isotope 13C technique, and through planting wheat (Triticum aestivum L., C3 crop) on a soil having been planted with maize (Zea mays L., C4 crop) for many years, this paper studied the effects of elevated atmospheric CO2 and nitrogen application on the delta 13C value of soil emitted CO2 and the wheat rhizosphere respiration. With the growth of wheat, the delta 13C value of soil emitted CO2 had a gradual decrease. Elevated atmospheric CO2 concentration (200 micromol mol(-1)) decreased the delta 13C value of emitted CO2 at booting and heading stages significantly when the nitrogen application rate was 250 kg hm(-2) (HN), and at jointing and booting stages significantly when the nitrogen application rate was 150 kg hm(-2) (LN). Nevertheless, the elevated atmospheric CO2 promoted the proportions of wheat rhizosphere respiration to soil respiration at booting and heading stages significantly. From jointing stage to maturing stage, the proportions of wheat rhizosphere respiration to soil respiration were 24%-48% (HN) and 21%-48% (LN) under elevated atmospheric CO2, and 20%-36% (HN) and 19%-32% (LN) under ambient atmospheric CO2. Under both elevated and ambient atmospheric CO2 concentrations, the delta 13C value of emitted CO2 and the rhizosphere respiration had different responses to the increased nitrogen application rate, and there was a significant interactive effect of atmospheric CO2 concentration and nitrogen application rate on the wheat rhizosphere respiration at jointing stage.

[Molecular typing of isolates from two dysentery outbreaks in Chengdu, through pulsed field gel electrophoresis technology].

OBJECTIVE: Using pulsed field gel electrophoresis (PFGE) and polymerase chain reaction (PCR) typing to analyze strains isolated from two outbreaks caused by Shigella sonnei and to trace the source of infection. METHODS: Virulence genes ipaH and ial were detected by PCR and PFGE was used to subtype the isolates. Patterns were compared, using the software BioNumerics. RESULTS: Within the 54 isolates, all were ipaH positive with 48 as ial positive. Strains from the Chongzhou outbreak were clustered into 4 PFGE patterns, with the predominant pattern accounted for 72% of the analyzed strains. The pattern of strains isolated from the cold pork with sauce was identical to the predominant pattern. The strains from Dayi outbreak were clustered into 8 PFGE patterns and the predominant pattern accounted for 56% of the test strains. CONCLUSION: Strains from the two outbreaks were quite different and the 'cold pork with sauce' seemed to be the major source of infection, causing the outbreak of diarrhea in Chongzhou. The sources of infection of the Dayi outbreak might be complicated whereas PFGE showed a discriminatory and reproducible laboratory tool in the epidemiologic investigation on outbreaks of diarrhea.