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multidrug resistant tuberculosis

Cheon Tae Kim, Tae-Ok Kim, Hong-Joon Shin, Young Chun Ko, Yeong Hun Choe, Hak-Ryul Kim, Yong-Soo Kwon
Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment. This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11), or both, either sequentially (n=10) or in co-administration (n=1), for more than 1 month, combined with a World Health Organization-recommended regimen. Of these, 49 (80.3%) were men and 12 (19.7%) were women. The median age was 53 years (interquartile range [IQR]=38...
March 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
March 7, 2018: European Journal of Medicinal Chemistry
Daniela Munro-Rojas, Esdras Fernandez-Morales, José Zarrabal-Meza, Ma Teresa Martínez-Cazares, Aurora Parissi-Crivelli, Javier Fuentes-Domínguez, Marie Nancy Séraphin, Michael Lauzardo, Jorge Alberto González-Y-Merchand, Sandra Rivera-Gutierrez, Roberto Zenteno-Cuevas
BACKGROUND: Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. METHODS: In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. FINDINGS: The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%)...
2018: PloS One
Nicholas Agyepong, Usha Govinden, Alex Owusu-Ofori, Sabiha Yusuf Essack
Background: Multidrug-resistant Gram-negative bacteria have emerged as major clinical and therapeutic dilemma in hospitals in Ghana.To describe the prevalence and profile of infections attributable to multidrug-resistant Gram-negative bacteria among patients at the Komfo Anokye Teaching Hospital in the Ashanti region of Ghana. Methods: Bacterial cultures were randomly selected from the microbiology laboratory from February to August, 2015. Bacterial identification and minimum inhibitory concentrations were conducted using standard microbiological techniques and the Vitek-2 automated system...
2018: Antimicrobial Resistance and Infection Control
Smriti Srivastava, Devla Bimal, Kapil Bohra, Balram Singh, Prija Ponnan, Ruchi Jain, Mandira Varma-Basil, Jyotirmoy Maity, M Thirumal, Ashok K Prasad
A series of β-d-ribofuranosyl coumarinyl-1,2,3-triazoles have been synthesized by Cu-catalyzed cycloaddition reaction between azidosugar and 7-O-/7-alkynylated coumarins in 62-70% overall yields. The in vitro antimycobacterial activity evaluation of the synthesized triazolo-conjugates against Mycobacterium tuberculosis revealed that compounds were bactericidal in nature and some of them were found to be more active than one of the first line antimycobacterial drug ethambutol against sensitive reference strain H37Rv, and 7 to 420 times more active than all four first line antimycobacterial drugs (isoniazid, rifampicin, ethambutol and streptomycin) against multidrug resistant clinical isolate 591...
February 27, 2018: European Journal of Medicinal Chemistry
Vasileios S Skouras, Ioannis Kalomenidis
PURPOSE OF REVIEW: To summarize data regarding categories, detection methods, prevalence and patterns of drug resistance among patients with tuberculous pleural effusion (TPE) and to comment on the management of suspected drug-resistant TPE. RECENT FINDINGS: Pleural and pulmonary tuberculosis (TB) present similar patterns of drug resistance. Approximately 10% and 6-10% of pleural Mycobacterium tuberculosis isolates are resistant to at least one first-line anti-TB drug or at least isoniazid, respectively...
March 9, 2018: Current Opinion in Pulmonary Medicine
Anthony L Byrne, Greg J Fox, Ben J Marais
Diagnostic and treatment delays contribute to increased death and disability among the 490,000 adults and children who develop multidrug-resistant (MDR) tuberculosis every year. Since the treatment of MDR tuberculosis is complex, costly and often toxic, tuberculosis control programs should prioritize strategies to prevent drug-resistant tuberculosis. Opportunities to limit transmission and prevent disease progression in close contacts of MDR tuberculosis cases are often neglected. Effective MDR tuberculosis preventive strategies could minimize the costs for patients and healthcare systems...
March 9, 2018: Future Microbiology
Liping Yan, Xiaohong Kan, Limei Zhu, Kaijin Xu, Jianjun Yin, Li Jie, Yong Li, Ji Yue, Wenyu Cui, Juan Du, Lihua Wang, Shouyong Tan, Xiangao Jiang, Zhong Zeng, Shenghui Xu, Lin Wang, Yu Chen, Weiguo He, Xusheng Gao, Dapeng Bai, Chengjie Zhao, Xiaofeng Yan, Yuyin Zhu, Yumei Fan, Lanpin Xie, Aihua Deng, Qing Zhang, Heping Xiao
PURPOSE: We designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). METHODS: We enrolled 917 sputum smear-positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin...
March 5, 2018: Clinical Therapeutics
Marie Sylvianne Rabodoarivelo, A Brandao, M C Cergole Novella, A G C Bombonatte, B Imperiale, N Rakotosamimanana, N Morcillo, V Rasolofo, J C Palomino, A Martin
Background: In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance. Methods: This was a multicenter study...
January 2018: International Journal of Mycobacteriology
Nontuthuko E Maningi, Luke T Daum, John D Rodriguez, Halima M Said, Remco P H Peters, John Osei Sekyere, Gerald W Fischer, James P Chambers, P Bernard Fourie
Modern advances in genomics provide an opportunity to re-interpret historical bacterial culture collections. In this study, genotypic antibiotic resistance profiles of Mycobacterium tuberculosis isolates from an historical 20-year-old multidrug-resistant tuberculosis (MDR-TB) culture collection in South Africa are described. DNA samples extracted from the phenotypically MDR-TB isolates (n=240) were assayed by Hain line probe assay (LPA) for the confirmation of MDR-TB and by Illumina Miseq whole genome sequencing (WGS) for the characterization of mutations in eight genes ( rpo B, kat G, inh A, rps L, pnc A, emb B, gyr A and rrs ) that are known to code for resistance to commonly used anti-TB agents...
March 7, 2018: Journal of Clinical Microbiology
Xavier Carette, John Platig, David C Young, Michaela Helmel, Albert T Young, Zhe Wang, Lakshmi-Prasad Potluri, Cameron Stuver Moody, Jumei Zeng, Sladjana Prisic, Joseph N Paulson, Jan Muntel, Ashoka V R Madduri, Jorge Velarde, Jacob A Mayfield, Christopher Locher, Tiansheng Wang, John Quackenbush, Kyu Y Rhee, D Branch Moody, Hanno Steen, Robert N Husson
Tuberculosis is the leading killer among infectious diseases worldwide. Increasing multidrug resistance has prompted new approaches for tuberculosis drug development, including targeted inhibition of virulence determinants and of signaling cascades that control many downstream pathways. We used a multisystem approach to determine the effects of a potent small-molecule inhibitor of the essential Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB. We observed differential levels of phosphorylation of many proteins and extensive changes in levels of gene expression, protein abundance, cell wall lipids, and intracellular metabolites...
March 6, 2018: MBio
Qiao Liu, Peng Lu, Leonardo Martinez, Haitao Yang, Wei Lu, Xiaoyan Ding, Limei Zhu
BACKGROUND: Few prospective cohort studies, none in China, have investigated the relationship between treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients and sputum culture conversion. Factors affecting the time of the culture conversion throughout the whole course of the treatment have rarely been investigated. METHODS: This study was performed in four cities in Jiangsu province, China. MDR-TB patients were consecutively enrolled between December 2011 and March 2014...
March 6, 2018: BMC Infectious Diseases
Diana Machado, João Perdigão, Isabel Portugal, Marco Pieroni, Pedro A Silva, Isabel Couto, Miguel Viveiros
With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes...
March 3, 2018: Antibiotics
Gunar Günther, Frank van Leth, Sofia Alexandru, Neus Altet, Korkut Avsar, Didi Bang, Raisa Barbuta, Graham Bothamley, Ana Ciobanu, Valeriu Crudu, Manfred Danilovits, Martin Dedicoat, Raquel Duarte, Gina Gualano, Heinke Kunst, Wiel de Lange, Vaira Leimane, Anne-Marie McLaughlin, Cecile Magis-Escurra, Inge Muylle, Veronika Polcová, Cristina Popa, Rudolf Rumetshofer, Alena Skrahina, Varvara Solodovnikova, Victor Spinu, Simon Tiberi, Piret Viiklepp, Christoph Lange
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less and cure rates are even lower. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by WHO and alternative simplified definitions. RESULTS: 380 patients with MDR-TB were recruited and followed-up between 2010 and 2014 in 16 European countries...
March 6, 2018: American Journal of Respiratory and Critical Care Medicine
T Song, L-J Li, J-L Liu, S-J Geng
OBJECTIVE: To investigate the relationship between changes in CD4- and CD8-positive immune cells and TNF-α in the peripheral blood of patients affected by multidrug-resistant and extensively drug-resistant tuberculosis. PATIENTS AND METHODS: 179 patients suffering from tuberculosis treated in the Chest Hospital of Hebei from April 2010 to December 2015 were selected for the study. There were 47 cases affected by drug-resistant tuberculosis and 132 cases affected by non-drug-resistant tuberculosis...
February 2018: European Review for Medical and Pharmacological Sciences
T Baird, E Donnan, C Coulter, G Simpson, A Konstantinos, G Eather
SETTINGp: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern worldwide. In Australia, although the incidence of MDR-TB remains low, Queensland is at an increased risk due to its proximity to Papua New Guinea (PNG). OBJECTIVE: To examine the epidemiology, clinical features and outcomes of MDR-TB in Queensland, with a comparison between cross-border PNG and non-cross-border patients. DESIGN: Retrospective case series of all MDR-TB patients in Queensland between 1 January 2000 and 31 December 2014...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
E Pavlenko, A Barbova, A Hovhannesyan, Z Tsenilova, A Slavuckij, B Shcherbak-Verlan, A Zhurilo, E Vitek, G Skenders, I Sela, A M Cabibbe, D M Cirillo, P de Colombani, M Dara, A Dean, M Zignol, A Dadu
SETTING: The true prevalence of multidrug-resistant tuberculosis (MDR-TB) in Ukraine is not known. Available data are a decade old and limited to only one province. OBJECTIVE: To determine the prevalence of MDR-TB among new and previously treated TB cases in Ukraine and explore the risk factors associated with drug resistance. METHODS: A total of 1550 sputum smear-positive pulmonary TB patients were recruited from 40 clusters throughout Ukraine...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
Gladys Kigozi, Michelle Engelbrecht, Christo Heunis, André Janse van Rensburg
BACKGROUND: In 2012, the World Health Organization launched guidelines for systematically investigating contacts of persons with infectious tuberculosis (TB) in low- and middle-income countries. As such, it is necessary to understand factors that would influence successful scale-up. This study targeted household contacts of newly-diagnosed infectious TB patients in the Mangaung Metropolitan district to explore factors associated with non-attendance of clinical evaluation. METHOD: In September-October 2016, a pilot study of household contacts was conducted...
March 5, 2018: BMC Infectious Diseases
Stephen Osei-Wusu, Michael Amo Omari, Adwoa Asante-Poku, Isaac Darko Otchere, Prince Asare, Audrey Forson, Jacob Otu, Martin Antonio, Dorothy Yeboah-Manu
Background: Drug resistance surveillance is crucial for tuberculosis (TB) control. Therefore, our goal was to determine the prevalence of second-line anti-TB drug resistance among diverse primary drug-resistant Mycobacterium tuberculosis complex (MTBC) isolates in Ghana. Materials and methods: One hundred and seventeen MTBC isolates with varying first-line drug resistance were analyzed. Additional resistance to second-line anti-TB drugs (streptomycin [STR], amikacin [AMK] and moxifloxacin [MOX]) was profiled using the Etest and GenoType MTBDRsl version 2...
2018: Infection and Drug Resistance
Sadia Naz, Umar Farooq, Sajid Ali, Rizwana Sarwar, Sara Khan, Ruben Abagyan
Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the α-subunit of Tryptophan synthase (α-TRPS) from Mycobacterium tuberculosis essential for bacterial survival...
March 3, 2018: Journal of Biomolecular Structure & Dynamics
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