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multidrug resistant tuberculosis

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https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#1
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28092681/genomic-analysis-of-globally-diverse-mycobacterium-tuberculosis-strains-provides-insights-into-the-emergence-and-spread-of-multidrug-resistance
#2
Abigail L Manson, Keira A Cohen, Thomas Abeel, Christopher A Desjardins, Derek T Armstrong, Clifton E Barry, Jeannette Brand, Sinéad B Chapman, Sang-Nae Cho, Andrei Gabrielian, James Gomez, Andreea M Jodals, Moses Joloba, Pontus Jureen, Jong Seok Lee, Lesibana Malinga, Mamoudou Maiga, Dale Nordenberg, Ecaterina Noroc, Elena Romancenco, Alex Salazar, Willy Ssengooba, A A Velayati, Kathryn Winglee, Aksana Zalutskaya, Laura E Via, Gail H Cassell, Susan E Dorman, Jerrold Ellner, Parissa Farnia, James E Galagan, Alex Rosenthal, Valeriu Crudu, Daniela Homorodean, Po-Ren Hsueh, Sujatha Narayanan, Alexander S Pym, Alena Skrahina, Soumya Swaminathan, Martie Van der Walt, David Alland, William R Bishai, Ted Cohen, Sven Hoffner, Bruce W Birren, Ashlee M Earl
Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28089787/antituberculosis-drugs-reducing-efflux-increasing-activity
#3
REVIEW
Liliana Rodrigues, Tanya Parish, Meenakshi Balganesh, José A Ainsa
In mycobacteria, it was assumed that efflux pumps only had a marginal role in drug resistance. In recent years, owing to the need to find novel drugs against multidrug-resistant tuberculosis, it has become clear that efflux should not be ignored. Although efflux inhibitors have been very useful for characterizing in vitro the properties of efflux pumps, their usefulness in vivo is limited because of their toxicity. Alternatively, programs aimed at discovering novel drugs for treating tuberculosis should implement strategies to characterize efflux liability of candidate drugs...
January 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28089216/diabetes-is-associated-with-severe-adverse-events-in-multidrug-resistant-tuberculosis
#4
Marcela Muñoz-Torrico, José Caminero-Luna, Giovanni Battista Migliori, Lia D'Ambrosio, José Luis Carrillo-Alduenda, Héctor Villareal-Velarde, Alfredo Torres-Cruz, Héctor Flores-Vergara, Dina Martínez-Mendoza, Cecilia García-Sancho, Rosella Centis, Miguel Ángel Salazar-Lezama, Rogelio Pérez-Padilla
INTRODUCTION: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City...
January 11, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/28087944/laboratory-diagnosis-and-susceptibility-testing-for-mycobacterium-tuberculosis
#5
Gary W Procop
The laboratory, which utilizes some of the most sophisticated and rapidly changing technologies, plays a critical role in the diagnosis of tuberculosis. Some of these tools are being employed in resource-challenged countries for the rapid detection and characterization of Mycobacterium tuberculosis. Foremost, the laboratory defines appropriate specimen criteria for optimal test performance. The direct detection of mycobacteria in the clinical specimen, predominantly done by acid-fast staining, may eventually be replaced by rapid-cycle PCR...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28086877/treating-the-invisible-gaps-and-opportunities-for-enhanced-tb-control-along-the-thailand-myanmar-border
#6
Naomi Tschirhart, Sein Sein Thi, Lei Lei Swe, Francois Nosten, Angel M Foster
BACKGROUND: In Thailand's northwestern Tak province, contextual conditions along the border with Myanmar pose difficulties for TB control among migrant populations. Incomplete surveillance data, migrant patient mobility, and loss to follow-up make it difficult to estimate the TB burden and implement effective TB control measures. This multi-methods study examined tuberculosis, tuberculosis and human immunodeficiency virus co-infection, and multidrug-resistant tuberculosis treatment accessibility for migrants and refugees in Tak province, health system response, and public health surveillance...
January 13, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28081227/diagnostic-accuracy-of-genexpert-mtb-rif-assay-in-comparison-to-conventional-drug-susceptibility-testing-method-for-the-diagnosis-of-multidrug-resistant-tuberculosis
#7
Pratikshya Pandey, Narayan Dutt Pant, Komal Raj Rijal, Bhawana Shrestha, Sirita Kattel, Megha Raj Banjara, Bhagwan Maharjan, Rajendra Kc
Xpert MTB/RIF assay is regarded as a great achievement of modern medicine for the rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB). The main purpose of this study was to determine the performance of Xpert MTB/RIF assay compared to conventional drug susceptibility testing (DST) method for the diagnosis of MDR-TB. A comparative cross sectional study was carried out at German-Nepal Tuberculosis Project, Kathmandu, Nepal, from April 2014 to September 2014. A total of 88 culture positive clinical samples (83 pulmonary and 5 extra-pulmonary) received during the study period were analyzed for detection of multidrug-resistant tuberculosis by both GeneXpert MTB/RIF assay and conventional DST method...
2017: PloS One
https://www.readbyqxmd.com/read/28073344/multidrug-resistant-tuberculosis-mdr-tb-disease-burden-in-china-a-systematic-review-and-spatio-temporal-analysis
#8
Peipei Ding, Xiaowen Li, Zhongwei Jia, Zuhong Lu
BACKGROUND: Surveillance data on the proportion of incident TB cases with MDR was limited and there is no systematic study of MDR-TB in China to date. Our aim was to estimate MDR-TB disease burden in 2012 and change trends during 2003-2012 using spatio-temporal systematic analysis. METHODS: We systematically searched Chinese and English databases for primary articles and reviews that contain MDR-TB survey data about China during the period of 2003-2012. We estimated the proportion of incident TB cases with MDR in cities which had no data to report in 2012 by Kriging spatial interpolation analysis...
January 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28071975/dynamics-of-fluoroquinolones-induced-resistance-in-dna-gyrase-of-mycobacterium-tuberculosis
#9
Bharati Pandey, Sonam Grover, Chetna Tyagi, Sukriti Goyal, Salma Jamal, Aditi Singh, Jagdeep Kaur, Abhinav Grover
DNA gyrase is a validated target of fluoroquinolones which are key components of multidrug resistance (MDR) TB treatment. Most frequent occurring mutations associated with high level of resistance to fluoroquinolone in clinical isolates of TB patients are A90V, D94G and A90V-D94G (double mutant), present in the larger subunit of DNA Gyrase. In order to explicate the molecular mechanism of drug resistance corresponding to these mutations, molecular dynamics and mechanics approach was applied. Structure based molecular docking of complex comprised of DNA bound with Gyrase A (large subunit) and Gyrase C (small subunit) with moxifloxacin revealed high binding affinity to wild type with considerably high Glide XP docking score of -7...
January 10, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28071153/novel-chemical-scaffolds-for-inhibition-of-rifamycin-resistant-rna-polymerase-discovered-from-high-throughput-screening
#10
Nathan T Scharf, Vadim Molodtsov, Arrin Kontos, Katsuhiko S Murakami, George A Garcia
Rifampin has been a cornerstone of tuberculosis (TB) treatment since its introduction. The rise of multidrug-resistant and extensively drug-resistant TB makes the development of novel therapeutics effective against these strains an urgent need. Site-specific mutations in the target enzyme of rifampin, RNA polymerase (RNAP) comprises the majority (~97%) of rifamycin-resistant (Rif(R)) strains of Mycobacterium tuberculosis (MTB). To identify novel inhibitors of bacterial RNAP, an in vitro plasmid-based transcription assay that uses malachite green (MG) to detect transcribed RNA containing MG aptamers was developed...
December 1, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#11
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto-)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of TB patients treated with amikacin or kanamycin in the period 2000 - 2012.Patients with culture-confirmed multi- or extensively drug resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28068907/hospitalized-care-for-mdr-tb-in-port-harcourt-nigeria-a-qualitative-study
#12
Kingsley Lezor Bieh, Ralf Weigel, Helen Smith
BACKGROUND: In Nigeria multidrug-resistant tuberculosis (MDR-TB) is prevalent in 2.9% of new TB cases and 14% of retreatment cases, and the country is one of 27 with high disease burden globally. Patients are admitted and confined to one of ten MDR-TB treatment facilities throughout the initial 8 months of treatment. The perspectives of MDR-TB patients shared on social media and in academic research and those of providers are limited to experiences of home-based care. In this study we explored the views of hospitalised MDR-TB patients and providers in one treatment facility in Nigeria, and describe how their experiences are linked to accessibility of care and support services, in line with international goals...
January 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28062386/rna-expression-analysis-of-efflux-pump-genes-in-clinical-isolates-of-multidrug-resistant-and-extensively-drug-resistant-mycobacterium-tuberculosis-in-south-korea
#13
Tae Sang Oh, Young Jin Kim, Hee Yoon Kang, Chang-Ki Kim, Sun Young Cho, Hee Joo Lee
Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is an important communicable disease. Various mechanisms of resistance to antituberculosis drugs have been reported; these are principally mutations in target genes. However, not all M. tuberculosis resistance can be explained by mutations in such genes. Other resistance mechanisms associated with drug transport, such as efflux pumps, have also been reported. In this study, we investigated the expression levels of three putative efflux pumps and mutations in target genes associated with injectable agents and fluoroquinolones with clinical MDR and XDR-TB isolates...
January 3, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28061832/high-rates-of-multidrug-resistant-and-rifampicin-resistant-tuberculosis-among-re-treatment-cases-where-do-they-come-from
#14
Romain Ragonnet, James M Trauer, Justin T Denholm, Ben J Marais, Emma S McBryde
BACKGROUND: Globally 3.9% of new and 21% of re-treatment tuberculosis (TB) cases are multidrug-resistant or rifampicin-resistant (MDR/RR), which is often interpreted as evidence that drug resistance results mainly from poor treatment adherence. This study aims to assess the respective contributions of the different causal pathways leading to MDR/RR-TB at re-treatment. METHODS: We use a simple mathematical model to simulate progression between the different stages of disease and treatment for patients diagnosed with TB...
January 6, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28057421/preparation-and-biological-evaluation-of-ethionamide-mesoporous-silicon-nanoparticles-against-mycobacterium-tuberculosis
#15
Nuno Vale, Alexandra Correia, Sara Silva, Patrícia Figueiredo, Ermei Mäkilä, Jarno Salonen, Jouni Hirvonen, Jorge Pedrosa, Hélder A Santos, Alexandra Fraga
Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28049180/group-5-drugs-for-multidrug-resistant-tuberculosis-is-the-glass-half-full-or-half-empty
#16
EDITORIAL
Giovanni Sotgiu, Giovanni Battista Migliori
No abstract text is available yet for this article.
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28049171/group-5-drugs-for-multidrug-resistant-tuberculosis-individual-patient-data-meta-analysis
#17
Greg J Fox, Andrea Benedetti, Helen Cox, Won-Jung Koh, Piret Viiklepp, Shama Ahuja, Geoffrey Pasvol, Dick Menzies
The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28044301/primary-pulmonary-mucinous-colloid-adenocarcinoma-that-arose-in-the-cavernomyoplasty-area-in-a-patient-with-tuberculosis-a-rare-case-report
#18
Neşe A Yener, Nesrin Sariman, Mehmet M Atasoy, Ahmet Midi, Alpay Örki
Primary pulmonary mucinous (colloid) adenocarcinoma is a rare type of lung cancer. Its arising in the cavernomyoplasty area has not been reported before. We here describe a sixty-year-old man with a previous history of multidrug-resistant and surgically-treated tuberculosis who was diagnosed as primary mucinous adenocarcinoma in the cavernomyoplasty site. We discuss the relevant literature on this rare entity.
2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28043788/comparison-of-bacteriological-conversion-and-treatment-outcomes-among-mdr-tb-patients-with-and-without-diabetes-in-mexico-preliminary-data
#19
M Muñoz-Torrico, J Caminero Luna, G B Migliori, L D'Ambrosio, J L Carrillo-Alduenda, H Villareal-Velarde, A Torres-Cruz, H Flores-Ergara, D Martínez-Mendoza, C García-Sancho, R Centis, M Á Salazar-Lezama, R Pérez-Padilla
: Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City...
December 30, 2016: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28043641/association-of-slow-recovery-of-mycobacterium-africanum-infected-patients-posttreatment-with-high-content-of-persister-like-bacilli-in-pretreatment-sputum
#20
Leopold D Tientcheu, Andrew Bell, Oumie Secka, Abigail Ayorinde, Jacob Otu, Nathalie J Garton, Jayne S Sutherland, Martin O Ota, Martin Antonio, H M Dockrell, Beate Kampmann, Michael R Barer
OBJECTIVES/BACKGROUND: Mycobacterium africanum that causes 40% of tuberculosis (TB) in West Africa grows more slowly in culture and has similar transmission capacity compared with Mycobacterium tuberculosis, but M. africanum-exposed contacts progress more slowly to active disease. The presence of lipid body (LB) containing M. tuberculosis complex (MTBC) cells in sputum samples has been associated with mycobacterial transcriptomes indicating slow or no growth and persister-like antibiotic tolerance...
December 2016: International Journal of Mycobacteriology
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