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multidrug resistant tuberculosis

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https://www.readbyqxmd.com/read/28545050/prevalence-and-extent-of-heteroresistance-by-next-generation-sequencing-of-multidrug-resistant-tuberculosis
#1
Darwin J Operario, Alexander F Koeppel, Stephen D Turner, Yongde Bao, Suporn Pholwat, Sayera Banu, Suporn Foongladda, Stellah Mpagama, Jean Gratz, Oleg Ogarkov, Svetlana Zhadova, Scott K Heysell, Eric R Houpt
Amplicon-based Next Generation Sequencing (NGS) is an emerging method for Mycobacterium tuberculosis drug susceptibility testing (DST) but has not been well described. We examined 158 clinical multidrug-resistant M. tuberculosis isolates via NGS of 11 resistance-associated gene regions covering 3519 nucleotides. Across these gene regions, complete resistance or heteroresistance (defined as 1%-99% mutation) was present in at least one isolate in 6.3% of loci. The number of isolates with heteroresistance was highest for gyrA codon 94, rpoB codons 526 and 531, and embB codons 306, 372 and 406 (range 11-26% of isolates exhibited heteroresistance)...
2017: PloS One
https://www.readbyqxmd.com/read/28540155/low-levels-of-extensively-drug-resistant-tuberculosis-among-multidrug-resistant-tuberculosis-isolates-and-their-relationship-to-risk-factors-surveillance-in-tehran-iran-2006-to-2014
#2
Alireza Hadizadeh Tasbiti, Shamsi Yari, Mostafa Ghanei, Mohammad Ali Shokrgozar, Abolfazl Fateh, Ahmadreza Bahrmand
OBJECTIVES: Extensively drug-resistant tuberculosis (XDR-TB) is more expensive and difficult to treat than multidrug-resistant tuberculosis (MDR-TB), and outcomes for patients are much worse; therefore, it is important that clinicians understand the magnitude and distribution of XDR-TB. We conducted a retrospective study to compare the estimated incidence of and risk factors for M/XDR-TB with those of susceptible TB controls. METHODS: Sputum culture and drug susceptibility testing (DST) were performed in patients with known or suspected TB...
April 2017: Osong Public Health and Research Perspectives
https://www.readbyqxmd.com/read/28539499/reply-to-anthony-et-al-protecting-pyrazinamide-a-priority-for-improving-outcomes-in-multidrug-resistant-tuberculosis-treatment
#3
M O Fofana, D W Dowdy
No abstract text is available yet for this article.
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28534009/genomic-insight-into-mechanisms-of-reversion-of-antibiotic-resistance-in-multidrug-resistant-mycobacterium-tuberculosis-induced-by-a-nanomolecular-iodine-containing-complex-fs-1
#4
Aleksandr I Ilin, Murat E Kulmanov, Ilya S Korotetskiy, Rinat A Islamov, Gulshara K Akhmetova, Marina V Lankina, Oleg N Reva
Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28533187/host-directed-therapies-offer-novel-opportunities-for-the-fight-against-tuberculosis
#5
REVIEW
Arnaud Machelart, Ok-Ryul Song, Eik Hoffmann, Priscille Brodin
Tuberculosis (TB) remains a leading global health problem that is exacerbated by the emergence of multidrug and extensively drug-resistant Mycobacterium tuberculosis strains. Control of the disease requires novel therapeutic strategies. Modulating host homeostasis appears to be a promising approach, and recent studies have identified novel potential host targets and compounds that could be investigated for host-directed therapies (HDTs). Moreover, the recent development of intracellular high-throughput phenotypic assays makes it possible to screen large libraries of compounds to identify more rapidly new effectors for mycobacterial elimination...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533124/the-novel-gene-mtb192-is-a-candidate-marker-for-the-detection-of-multidrug-resistant-mycobacterium-tuberculosis-strains
#6
Junhua Chen, Li Jiang, Wei Su, Gaihuan Zheng, Xu Hongmei
BACKGROUND: Multi-drug resistant tuberculosis (TB) is one of the most main threats to the global TB control work at present. And it's very difficult to detect. From a screen of differentially expressed genes in multidrug-resistant tuberculosis (MDR-TB) strains, we identified a new gene, mtb192. In the present study, we verified the association of mtb192 with TB drug resistance by detecting its expression in clinical isolates from paediatric TB patients. MATERIALS AND METHODS: The homology of mtb192 was analysed by gene blasting in GenBank...
May 19, 2017: Gene
https://www.readbyqxmd.com/read/28533094/population-implications-of-the-use-of-bedaquiline-in-people-with-extensively-drug-resistant-tuberculosis-are-fears-of-resistance-justified
#7
REVIEW
Amber Kunkel, Jennifer Furin, Ted Cohen
Global rollout of the new antituberculosis drug bedaquiline has been slow, in part reflecting concerns about spread of bedaquiline resistance. Acquired resistance to bedaquiline is especially likely in patients with extensively drug-resistant (XDR) tuberculosis. However, the very high mortality rates of patients with XDR not receiving bedaquiline, and promising cohort study results, suggest these patients also have greatest need for the drug. In this Personal View, we argue that resistance concerns should not forestall use of bedaquiline in patients with XDR tuberculosis...
May 19, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28529206/bedaquiline-for-the-treatment-of-multidrug-resistant-tuberculosis-another-missed-opportunity
#8
EDITORIAL
Lorenzo Guglielmetti
No abstract text is available yet for this article.
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28529205/effectiveness-and-safety-of-bedaquiline-containing-regimens-in-the-treatment-of-mdr-and-xdr-tb-a-multicentre-study
#9
Sergey E Borisov, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan-Willem Alffenaar, Andrey Maryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, Jose A Caminero, Isabel Carpena Martinez, Luigi Codecasa, Margareth Dalcolmo, Justin Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Alexey Filippov, Lina Davies Forsman, Mina Gaga, Julia-Amaranta Garcia-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Katerina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Juan Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Farokh Udwadia, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
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...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28528545/discovery-and-biosynthesis-of-gladiolin-a-burkholderia-gladioli-antibiotic-with-promising-activity-against-mycobacterium-tuberculosis
#10
Lijiang Song, Matthew Jenner, Joleen Masschelein, Cerith Jones, Matthew J Bull, Simon R Harris, Ruben C Hartkoorn, Anthony Vocat, Isolda Romero-Canelón, Paul Coupland, Gordon Webster, Matthew Dunn, Rebecca Weiser, Christopher Paisey, Stewart T Cole, Julian Parkhill, Eshwar Mahenthiralingam, Gregory L Challis
An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally-related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability...
May 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28527252/-characterization-of-clinical-isolates-of-mycobacterium-tuberculosis-from-hiv-positive-individuals-in-colombia-2012
#11
Claudia Castro, Alba Ricardo, Angie Zabaleta, Claudia Llerena, Gloria Puerto
INTRODUCTION: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. OBJECTIVE: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28523106/discovery-of-fluorine-containing-benzoxazinyl-oxazolidinones-for-the-treatment-of-multidrug-resistant-tuberculosis
#12
Hongyi Zhao, Yu Lu, Li Sheng, Zishuo Yuan, Bin Wang, Weiping Wang, Yan Li, Chen Ma, Xiaoliang Wang, Dongfeng Zhang, Haihong Huang
A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 μg/mL against drug-susceptible H37Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522948/evaluation-of-xpert-mtb-rif-assay-performance-in-the-diagnosis-of-abdominal-tuberculosis
#13
Suraj Kumar, Sawan Bopanna, Saurabh Kedia, Pratap Mouli, Rajan Dhingra, Rajesh Padhan, Mikashmi Kohli, Jigyasa Chaubey, Rohini Sharma, Prasenjit Das, S Dattagupta, Govind Makharia, S K Sharma, Vineet Ahuja
BACKGROUND/AIMS: The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population. METHODS: Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28520704/adverse-events-associated-with-treatment-of-multidrug-resistant-tuberculosis-in-china-an-ambispective-cohort-study
#14
Yang Zhang, Shanshan Wu, Yinyin Xia, Ni Wang, Lin Zhou, Jing Wang, Renfei Fang, Feng Sun, Mingting Chen, Siyan Zhan
BACKGROUND Adverse events are under-appreciated negative consequences that are significant clinical problems for patients undergoing anti-MDR-TB treatment due to longer duration of treatment and more need for concurrent use of multiple second-line drugs. The aim of this study was to determine the incidence of adverse events and their impact on MDR-TB therapy and treatment outcome, and to identify possible drug-event pairs in China. MATERIAL AND METHODS An ambispective cohort study was conducted based on hospital medical records, which included a retrospective study that enrolled 751 MDR-TB patients receiving standardized regimen between May 2009 and July 2013, and a follow-up investigation of treatment outcome conducted in December 2016 in China...
May 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28513917/fragment-screening-against-the-ethr-dna-interaction-by-native-mass-spectrometry
#15
Daniel Shiu-Hin Chan, Vitor Mendes, Sherine E Thomas, Brendan N McConnell, Dijana Matak-Vinković, Anthony G Coyne, Tom L Blundell, Christopher Abell
Native nanoelectrospray ionization mass spectrometry is an underutilized technique for fragment screening. In this study, the first demonstration is provided of the use of native mass spectrometry for screening fragments against a protein-DNA interaction. EthR is a transcriptional repressor of EthA expression in Mycobacterium tuberculosis (Mtb) that reduces the efficacy of ethionamide, a second-line anti-tubercular drug used to combat multidrug resistant Mtb strains. A small-scale fragment screening campaign was conducted against the EthR-DNA interaction using native mass spectrometry, and results were compared with those from differential scanning fluorimetry, a commonly used primary screening technique...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28513421/clinical-and-bacteriological-characteristics-associated-with-clustering-of-multidrug-resistant-tuberculosis
#16
J-Y J-Y Feng, L G Jarlsberg, K Salcedo, J Rose, M Janes, S-Y G Lin, D H Osmond, K C Jost, M K Soehnlen, J Flood, E A Graviss, E Desmond, P K Moonan, P Nahid, P C Hopewell, M Kato-Maeda
<h2>SETTING:</h2><p>The impact of the genetic characteristics of Mycobacterium tuberculosis on the clustering of multidrug-resistant tuberculosis (MDR-TB) has not been analyzed together with clinical and demographic characteristics.</p><h2>OBJECTIVE:</h2><p>To determine factors associated with genotypic clustering of MDR-TB in a community-basedstudy.</p><h2>DESIGN:</h2><p>We measured the proportion of clustered cases among MDR-TB patients and determined the impact of clinical and demographic characteristics and that of three M...
May 16, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28512556/pediatric-tuberculosis-in-northern-sardinia
#17
Maria Grazia Clemente, Elena Dore, Lidia Abis, Paola Molicotti, Stefania Zanetti, Paolina Olmeo, Roberto Antonucci
BACKGROUND AND OBJECTIVES: Migration flux is an increasing phenomenon in Italy, and it raises several public health issues and concerns in pediatric infectious diseases. This study investigated the clinical characteristics and outcomes of a pediatric population at high-risk for tuberculosis (TB) and the potential role of immigration as a risk factor. DESIGN: We performed an observational retrospective study of children referred to the only Pediatric Infectious Diseases Unit for Northern Sardinia over a 6-year-period (2009-2014)...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28511895/diagnostic-performance-of-anyplex-ii-mtb-mdr-xdr-for-detection-of-resistance-to-first-and-second-line-drugs-in-mycobacterium-tuberculosis
#18
F Pérez-García, M J Ruiz-Serrano, P López Roa, Fermín Acosta, Laura Pérez-Lago, D García-De-Viedma, E Bouza
PURPOSE: Genotypic methods have considerably improved the diagnosis of multidrug-resistant (MDR) tuberculosis. One of these tests is Anyplex II MTB/MDR/XDR (Anyplex). Our aim was to evaluate the diagnostic performance of this multiplex PCR. METHODS: We conducted our study on 47 MDR tuberculosis and 14 pan-susceptible strains. We evaluated the ability of Anyplex to detect resistance mutations in rpoB (rifampin [RIF]), katG and inhA (isoniazid [INH]), gyrA (fluoroquinolones [FLQ]), and rrs and eis (aminoglycosides [AMG])...
May 13, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28507117/pharmacokinetics-of-levofloxacin-in-multidrug-and-extensively-drug-resistant-tuberculosis-patients
#19
Natasha Van't Boveneind-Vrubleuskaya, Tatiana Seuruk, Kai van Hateren, Tridia van der Laan, Jos G W Kosterink, Tjip S van der Werf, Dick van Soolingen, Susan van den Hof, Alena Skrahina, Jan-Willem C Alffenaar
Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter to predict the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of treatment regimen at a dose of 15 mg/kg once daily...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28504628/-the-current-global-tuberculosis-state
#20
Christian Wejse, Troels Lillebæk, Ole Kirk, Pernille Ravn, Isik Somuncu Johansen, Åse Bengård Andersen
Despite an increase in the total number of tuberculosis (TB) patients globally, positive trends in reduction of prevalence and mortality are observed. However, high numbers of drug-resistant cases are threatening this trend. Multidrug-resistant and extensively resistant cases constitute an increasing challenge in many parts of the world also within the European region - especially in former Sovjet Republic nations. Point-of-care test systems potentially replacing microscopy and urine antigen detection systems are currently launched in many TB-high endemic countries improving TB detection rates...
May 15, 2017: Ugeskrift for Laeger
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