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https://www.readbyqxmd.com/read/29441052/harnessing-the-mtor-pathway-for-tuberculosis-treatment
#1
REVIEW
Pooja Singh, Selvakumar Subbian
Tuberculosis (TB) remains as one of the leading killer infectious diseases of humans. At present, the standard therapeutic regimen to treat TB comprised of multiple antibiotics administered for a minimum of six months. Although these drugs are useful in controlling TB burden globally, they have not eliminated the disease. In addition, the lengthy duration of treatment with multiple drugs contributes to patient non-compliance that can result in the development of drug resistant strains (MDR and XDR) of Mycobacterium tuberculosis (Mtb), the causative agent of TB...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29412643/the-expanding-diversity-of-mycobacterium-tuberculosis-drug-targets
#2
Samantha Wellington, Deborah T Hung
After decades of relative inactivity, a large increase in efforts to discover antitubercular therapeutics has brought insights into the biology of Mycobacterium tuberculosis (Mtb) and promising new drugs such as bedaquiline, which inhibits ATP synthase, and the nitroimidazoles delamanid and pretomanid, which inhibit both mycolic acid synthesis and energy production. Despite these advances, the drug discovery pipeline remains underpopulated. The field desperately needs compounds with novel mechanisms of action capable of inhibiting multi- and extensively drug -resistant Mtb (M/XDR-TB) and, potentially, nonreplicating Mtb with the hope of shortening the duration of required therapy...
February 15, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29395080/biophysical-and-biochemical-characterization-of-rv3405c-a-tetracycline-repressor-protein-from-mycobacterium-tuberculosis
#3
Akilandeswari Gopalan, Raghu Bhagavat, Nagasuma Chandra, Savithri Handanahal Subbarao, Alamelu Raja, Ramalingam Bethunaickan
Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is one among the deadliest pathogens in the world. Due to long treatment regimen, HIV co-infection, persistence of bacilli in latent form and development of XDR and TDR strains of Mtb, tuberculosis has posed serious concerns for managing the disease, and calls for discovery of new drugs and drug targets. Using a computational pipeline involving analysis of the structural models of the Mtb proteome and an analysis of the ATPome, followed by a series of filters to identify druggable proteins, solubility and length of the protein, several candidate proteins were shortlisted...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29390307/pulmonary-resection-in-the-treatment-of-multidrug-resistant-tuberculosis-a-case-series
#4
Lin Wang, Fan Xia, Feng Li, Xueqin Qian, Yijun Zhu, Hui Chen, Aoao Bian, Jun Wang, Min Zhang, Hongwei Li, Jiafu Han, Nan Jiang, Ning Xu, Yanzheng Song
Multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis (TB) are significant health problems throughout the world. Although the main treatment is medical, adjunctive surgical resection may increase the chance of cure in selected patients with MDR-TB or XDR-TB. This study aimed to present a case series of patients who underwent surgical resection for MDR-TB.Between March 2008 and November 2011, surgical resection was performed on 54 patients including 34 with MDR-TB and 20 with XDR-TB at the Departments of Surgery of Shanghai Public Health Clinical Center (Shanghai), Henan Chest Hospital (Henan), and Anhui Chest Hospital (Henan)...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29378718/clofazimine-for-treatment-of-pulmonary-extensively-drug-resistant-tuberculosis-in-china
#5
Qingfeng Wang, Yu Pang, Wei Jing, Yufeng Liu, Na Wang, Hongyun Yin, Qing Zhang, Zhizhong Ye, Min Zhu, Fujian Li, Ping Liu, Tingting Wu, Wei Chen, Wei Wu, Zhihua Qin, Chao Qiu, Qunyi Deng, Tao Xu, Jing Wang, Ru Guo, Yadong Du, Jun Wang, Hairong Huang, Xiaohong Chen, Naihui Chu
We performed a multicenter, prospective and randomized study to investigate the efficacy and safety of clofazimine (CLO) for treatment of extensively drug-resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR-TB were randomly assigned to either the control group or the CLO group, both of which received 36 months of individually customized treatment. The primary end-point was the time to sputum-culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion...
January 29, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29377374/identification-of-small-molecular-inhibitors-for-efflux-protein-rv2688c-of-mycobacterium-tuberculosis
#6
Rajender Vadija, Kiran Kumar Mustyala, Vasavi Malkhed, Ramasree Dulapalli, Hymavathi Veeravarapu, Ramesh Malikanti, Uma Vuruputuri
Mycobacterium tuberculosis (Mtb) is the pathogen, which causes Tuberculosis (TB). Development of Multidrug resistant (MDR) and extensively drug resistant (XDR) strains in Mtb is due to an efflux mechanism of antibiotics in the bacteria. The efflux pump proteins in the bacteria are implicated in the active efflux of antibiotics. The efflux pump protein, 'Fluoroquinolones export ATP-binding protein Rv2688c' (FEAB), is considered as a potential therapeutic target to prevent Tuberculosis. In the present work, in silico protocols are applied to identify inhibitors for the FEAB protein to arrest the efflux mechanism...
January 29, 2018: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29311073/the-validation-of-cycloserine-efficacy-in-treatment-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-in-beijing-china
#7
Xia Yu, Xiling Zeng, Wenhui Shi, Yanjie Hu, Wenjuan Nie, Naihui Chu, Hairong Huang
Cycloserine is recommended by the World Health Organization as a second line drug to treat multidrug-resistant tuberculosis(MDR TB), however its efficacy has never been sufficiently evaluated. To gain some insights into the value of cycloserine (Cs) for MDR TB treatment, in vitro bacteriostatic effect and patient validations were performed prospectively.The in vitro activity of Cs against 104 wild-type M. tuberculosis strains was determined, and serum Cs concentration was measured for 73 MDR TB patients 2 hours after administration...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29310751/multi-clonal-evolution-of-multi-drug-resistant-extensively-drug-resistant-mycobacterium-tuberculosis-in-a-high-prevalence-setting-of-papua-new-guinea-for-over-three-decades
#8
Arnold Bainomugisa, Evelyn Lavu, Stenard Hiashiri, Suman Majumdar, Alice Honjepari, Rendi Moke, Paison Dakulala, Grant A Hill-Cawthorne, Sushil Pandey, Ben J Marais, Chris Coulter, Lachlan Coin
An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012-2015 revealed that 95 belonged to a single modern Beijing sub-lineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation...
January 4, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29305096/automated-real-time-detection-of-drug-resistant-mycobacterium-tuberculosis-on-a-lab-on-a-disc-by-recombinase-polymerase-amplification
#9
I L G Law, J F C Loo, H C Kwok, H Y Yeung, C C H Leung, M Hui, S Y Wu, H S Chan, Y W Kwan, H P Ho, S K Kong
With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR...
January 2, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29297426/risk-factors-for-extensive-drug-resistance-in-multidrug-resistant-tuberculosis-cases-a-case-case-study
#10
L Guglielmetti, N Veziris, A Aubry, F Brossier, C Bernard, W Sougakoff, V Jarlier, J Robert
SETTINGS: Identification of extensively drug-resistant tuberculosis (XDR-TB) may be delayed because of the lack of availability of molecular testing for second-line drugs (SLDs). Early suspicion of XDR-TB is therefore necessary to avoid developing further drug resistance. OBJECTIVE: To identify the characteristics associated with XDR-TB among multidrug-resistant TB (MDR-TB) cases before the availability of second-line drug susceptibility testing (DST) results. METHODS: All MDR-TB cases with available second-line DST results recorded in France from 1998 to 2013 were classified as simple MDR-TB (no resistance to fluoroquinolones [FQs] or second-line injectable drugs [SLIDs]), pre-XDR-TB (resistance to FQs or SLIDs) and XDR-TB cases (resistance to both)...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29297425/extensively-drug-resistant-tuberculosis-in-myanmar-burden-and-mutations-causing-second-line-drug-resistance
#11
P W Ei, W W Aung, W W Nyunt, T L Swe, M M Htwe, S M Win, S T Aung, C L Chang, H-Y Lee, J S Lee
SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29297423/meropenem-clavulanate-for-drug-resistant-tuberculosis-a-follow-up-of-relapse-free-cases
#12
M C Payen, I Muylle, O Vandenberg, V Mathys, M Delforge, S Van den Wijngaert, N Clumeck, S De Wit
BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB), defined as TB caused by a Mycobacterium strain resistant to at least rifampicin, isoniazid, any fluoroquinolone and one of the injectable anti-tuberculosis drugs, remains a worldwide public health threat. Among repurposed drugs empirically used for XDR-TB cases, carbapenems have been studied in vitro and in animal models, with encouraging results. However, only short-term follow-up data from clinical studies are currently available...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29282012/comparison-of-line-probe-assay-to-bactec-mgit-960-system-for-susceptibility-testing-of-first-and-second-line-anti-tuberculosis-drugs-in-a-referral-laboratory-in-south-africa
#13
Nontuthuko E Maningi, Lesibana A Malinga, John F Antiabong, Ruth M Lekalakala, Nontombi M Mbelle
BACKGROUND: The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing and the emergence of extensively drug-resistant tuberculosis (XDR-TB) is a major challenge. Controlling resistance, reducing transmission and improving treatment outcomes in MDR/XDR-TB patients is reliant on susceptibility testing. Susceptibility testing using phenotypic methods is labour intensive and time-consuming. Alternative methods, such as molecular assays are easier to perform and have a rapid turn-around time...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29274493/1-3-5-triazaspiro-5-5-undeca-2-4-dienes-as-selective-mycobacterium-tuberculosis-dihydrofolate-reductase-inhibitors-with-potent-whole-cell-activity
#14
Xuan Yang, Wassihun Wedajo, Yoshiyuki Yamada, Sue-Li Dahlroth, Jason Jun-Long Neo, Thomas Dick, Wai-Keung Chui
The emergence of multi- and extensively-drug resistant tubercular (MDR- and XDR-TB) strains of mycobacteria has limited the use of existing therapies, therefore new drugs are needed. Dihydrofolate reductase (DHFR) has recently attracted much attention as a target for the development of anti-TB agents. This study aimed to develop selective M. tuberculosis DHFR inhibitors using rationale scaffolding design and synthesis, phenotype-oriented screening, enzymatic inhibitory study, whole cell on-target validation, molecular modeling, and in vitro DMPK determination to derive new anti-TB agents...
December 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29244096/treatment-of-pulmonary-tuberculosis-past-and-present
#15
Dmitry Borisovich Giller, Boris Dmitrievich Giller, Galina Vitalievna Giller, Galina Vladimirovna Shcherbakova, Anuar Bahtibaevich Bizhanov, Inga Igorevna Enilenis, Aleksey Aleksandrovich Glotov
OBJECTIVES: Surgical interventional has been key in the treatment of tuberculosis (TB) for a long time. Its importance diminished after the emergence of chemotherapy. However, the spread of rapid multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has led us to return to surgery to treat TB. Today, every second patient in Russia with destructive TB has either MDR or XDR TB, which is the reason for the low efficacy of conservative treatment. In 2015, treatment with drugs resulted in clinical recovery in only 29...
December 12, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29238270/treatment-of-latent-tuberculosis-infection
#16
REVIEW
Patrick Tang, James Johnston
The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and active TB has been ruled out, this is followed by an evaluation of the risks and benefits of LTBI treatment within the context of the regional epidemiology of TB and public health priorities...
2017: Current Treatment Options in Infectious Diseases
https://www.readbyqxmd.com/read/29229108/infection-control-genetic-assessment-of-drug-resistance-and-drug-susceptibility-testing-in-the-current-management-of-multidrug-extensively-resistant-tuberculosis-m-xdr-tb-in-europe-a-tuberculosis-network-european-trialsgroup-tbnet-study
#17
Graham H Bothamley, Christoph Lange
AIM: Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. METHODS: TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing...
November 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29212699/rapid-microarray-based-detection-of-rifampicin-isoniazid-and-fluoroquinolone-resistance-in-mycobacterium-tuberculosis-using-a-single-cartridge
#18
Juliane Havlicek, Beatrice Dachsel, Peter Slickers, Sönke Andres, Patrick Beckert, Silke Feuerriegel, Stefan Niemann, Matthias Merker, Ines Labugger
Rapid and robust identification of mutations in Mycobacterium tuberculosis complex (MTBC) strains mediating multidrug and extensively drug-resistant (M/XDR) phenotypes is crucial to combat the MDR tuberculosis (TB) epidemic. Currently available molecular TB drug susceptibility tests are either restricted to single targets/drugs (i.e. Xpert MTB/RIF) or aid the risk of cross-contaminations due to the design limitations of the open platform (i.e. line probe assays).With a good understanding of the technical and commercial boundaries we designed a test cartridge with an introduction of dried reagents, based on an oligonucleotide array, which has the ability to identify MTBC strains resistant to isoniazid, rifampicin and the fluoroquinolones...
December 6, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29201659/mental-disorders-and-drug-alcohol-use-in-patients-commencing-extensively-drug-resistant-tuberculosis-treatment
#19
J Scuffell, D Boccia, F Garcia Velarde, S R Leon, G Raviola, L Lecca, J T Galea
Mental disorders and alcohol/drug use worsen treatment outcomes for multidrug-resistant tuberculosis (TB), but data are lacking for extensively drug-resistant (XDR) TB. We investigated the association of baseline mental disorders and alcohol/drug use on XDR-TB treatment outcomes in a retrospective study of 53 XDR-TB Peruvian patients during 2010-2012. Logistic regression estimated the odds ratios for unfavourable XDR-TB treatment outcomes. Overall treatment success was 25%. Mental disorders and drug/alcohol use were found in respectively 22...
September 21, 2017: Public Health Action
https://www.readbyqxmd.com/read/29184888/targeting-dna-replication-and-repair-for-the-development-of-novel-therapeutics-against-tuberculosis
#20
REVIEW
Michael A Reiche, Digby F Warner, Valerie Mizrahi
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), an infectious disease which results in approximately 10 million incident cases and 1.4 million deaths globally each year, making it the leading cause of mortality from infection. An effective frontline combination chemotherapy exists for TB; however, this regimen requires the administration of four drugs in a 2 month long intensive phase followed by a continuation phase of a further 4 months with two of the original drugs, and is only effective for the treatment of drug-sensitive TB...
2017: Frontiers in Molecular Biosciences
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