Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Bedaquiline–Pretomanid–Linezolid Regimens for Drug-Resistant Tuberculosis

Background The bedaquiline–pretomanid–linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear. Methods We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated. Results A total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline–pretomanid–linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups. Conclusions A total of 84 to 93% of the participants across all four bedaquiline–pretomanid–linezolid treatment groups had a favorable outcome. The overall risk–benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486. opens in new tab.

Morphological and molecular identification of four Brazilian commercial isolates of Pleurotus spp. and cultivation on corncob

The species of Pleurotus have great commercial importance and adaptability for growth and fructification within a wide variety of agro-industrial lignocellulosic wastes. In this study, two substrates prepared from ground corncobs supplemented with rice bran and charcoal were tested for mycelium growth kinetics in test tubes and for the cultivation of four Pleurotus commercial isolates in polypropylene bags. The identification of the isolates was based on the morphology of the basidiomata obtained and on sequencing of the LSU rDNA gene. Three isolates were identified as P. ostreatus, and one was identified as P. djamor. All isolates had better in-depth mycelium development in the charcoal-supplemented substrate. In the cultivation experiment, the isolates reacted differently to the two substrates. One isolate showed particularly high growth on the substrate containing charcoal.<br>Espécies de Pleurotus têm grande importância comercial e adaptabilidade para crescimento e frutificação em uma ampla variedade de resíduos agro-industriais lignocelulósicos. Neste trabalho foram testados dois substratos à base de sabugo de milho triturado, suplementados com farelo de arroz e carvão vegetal, para avaliação da cinética de crescimento micelial em tubos de ensaio e produção em sacos de polipropileno, utilizando quatro isolados comerciais. O estudo taxonômico foi realizado com a análise da morfologia dos basidiomas obtidos em cultivo e pelo seqüenciamento do gene nLSU do DNAr, para certificar a identificação taxonômica. Os isolados tiveram melhor desenvolvimento micelial em profundidade no substrato suplementado com carvão vegetal. Em relação à produção, os isolados reagiram de formas distintas em função dos substratos, sendo significativamente melhor o substrato contendo carvão. Três isolados foram identificados como P. ostreatus e o outro foi identificado como P. djamor

Stimulation of Wood Degradation by Daedaleopsis confragosa and D. tricolor

Biological pretreatment of the lignocellulosic residues, in which white-rot fungi have a crucial role, has many advantages compared to the chemical, physical, and physico-chemical methods of delignification and therefore attracts increasing scientific attention. Regarding the fact that properties and capacities of the ligninolytic enzymes of Daedaleopsis spp. are still unknown, the aim of this study was to research how nitrogen sources and inducers affect the potential of Daedaleopsis confragosa and Daedaleopsis tricolor to degrade cherry sawdust. NH4NO3, (NH4)2SO4, and peptone were tested as nitrogen sources, while veratryl alcohol, p-anisidine, vanillic acid, and phenylmethylsulfonyl fluoride were the studied inducers. As Mn-dependent peroxidase and laccase were the leader enzymes and cherry sawdust/peptone medium the best stimulator of their activities, the effect of inducers on delignification potential of these species was studied during fermentation of that substrate. Veratryl alcohol was the best stimulator of laccase and phenylmethylsulfonyl fluoride of Mn-dependent peroxidase activity (27,610.0 and 1338.4 U/L, respectively). These inducers also increased cherry sawdust delignification selectivity, particularly in D. tricolor in the presence of phenylmethylsulfonyl fluoride (lignin:hemicellulose:cellulose = 32.1%:0.9%:11.7%). Owing to the presented results, studied species could have an important role in the phase of lignocellulose pretreatment in various biotechnological processes. © 2018, Springer Science+Business Media, LLC, part of Springer Nature