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Tuberculosis, antimicrobial drug resistance

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https://www.readbyqxmd.com/read/29891191/clofazimine-drug-susceptibility-testing-for-mycobacterium-tuberculosis-the-case-of-using-the-right-diluent
#1
Li-Hwei Sng, Justine Woei Ling Peh, Melody Tai Lee Kee, Nurhazirah Bte Mohd Ya'akob, Rick Twee-Hee Ong, Christopher W Wong, Cynthia Bin Eng Chee, Yee Tang Wang
Accurate and reliable drug susceptibility testing (DST) is essential for the effective treatment and control of tuberculosis. With the increase in drug-resistant organisms, newer and less conventional antimicrobial agents are used for treatment. Recently, we found an unprecedented rise in the number of clofazimine-resistant Mycobacterium tuberculosis isolates in our laboratory. An investigation found that this phenomenon was due to a change in the method of drug preparation. We performed studies to assess the impact of water and dimethyl sulfoxide (DMSO) as a final diluent for clofazimine drug testing...
June 8, 2018: Pathology
https://www.readbyqxmd.com/read/29848567/direct-whole-genome-sequencing-of-sputum-accurately-identifies-drug-resistant-mycobacterium-tuberculosis-faster-than-mgit-culture-sequencing
#2
Ronan M Doyle, Carrie Burgess, Rachel Williams, Rebecca Gorton, Helen Booth, James Brown, Josephine M Bryant, Jackie Chan, Dean Creer, Jolyon Holdstock, Heinke Kunst, Stefan Lozewicz, Gareth Platt, Erika Yara Romero, Graham Speight, Simon Tiberi, Ibrahim Abubakar, Marc Lipman, Timothy D McHugh, Judith Breuer
The current methods available to diagnose antimicrobial resistant Mycobacterium tuberculosis infections require positive culture or only test a limited number of resistance-associated mutations. Rapid, accurate identification of antimicrobial resistance enables prompt initiation of effective treatment. Here, we determine the utility of whole-genome sequencing (WGS) M. tuberculosis directly from routinely obtained diagnostic sputum samples to provide a comprehensive resistance profile compared to Mycobacterial Growth Indicator Tube (MGIT) WGS...
May 30, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29779917/antimicrobial-resistance-among-migrants-in-europe-a-systematic-review-and-meta-analysis
#3
Laura B Nellums, Hayley Thompson, Alison Holmes, Enrique Castro-Sánchez, Jonathan A Otter, Marie Norredam, Jon S Friedland, Sally Hargreaves
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings...
May 17, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29774213/a-rapid-growth-independent-antibiotic-resistance-detection-test-by-sybr-green-propidium-iodide-viability-assay
#4
Jie Feng, Rebecca Yee, Shuo Zhang, Lili Tian, Wanliang Shi, Wen-Hong Zhang, Ying Zhang
Antibiotic-resistant bacteria have caused huge concerns and demand innovative approaches for their prompt detection. Current antimicrobial susceptibility tests (AST) rely on the growth of the organisms which takes 1-2 days for fast-growing organisms and several weeks for slow growing organisms. Here, we show for the first time the utility of the SYBR Green I/propidium iodide (PI) viability assay for rapidly identifying antibiotic resistance in less than 30 min for major, antibiotic-resistant, fast-growing bacteria, such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae , and Acinetobacter baumannii for bactericidal and bacteriostatic agents and in 16 h for extremely rapid detection of drug resistance for isoniazid and pyrazinamide in slow-growing Mycobacterium tuberculosis ...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29767993/multi-metallic-microparticles-increase-the-potency-of-rifampicin-against-intracellular-mycobacterium-tuberculosis
#5
Timothy Ellis, Michele Chiappi, Andres Garcia-Trenco, Maryam Al-Ejji, Srijata Sarkar, Theoni K Georgiou, Milo Sebastian Peter Shaffer, Teresa D Tetley, Stephan Schwander, Mary P Ryan, Alexandra E Porter
Mycobacterium tuberculosis (M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29738954/antibacterial-and-anti-tb-tat-peptidomimetics-with-improved-efficacy-and-half-life
#6
Govind S Bhosle, Laxman Nawale, Amar M Yeware, Dhiman Sarkar, Moneesha Fernandes
Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid...
April 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29686657/naphthoquinone-derivatives-as-scaffold-to-develop-new-drugs-for-tuberculosis-treatment
#7
Priscila C B Halicki, Laís A Ferreira, Kelly C G De Moura, Paula F Carneiro, Karina P Del Rio, Tatiane Dos S C Carvalho, Maria do C F R Pinto, Pedro E A da Silva, Daniela F Ramos
Despite being a curable disease, tuberculosis (TB) remains a public health problem worldwide mainly due to lengthy treatment, as well as its toxic effects, TB/HIV co-infection and the emergence of resistant Mycobacterium tuberculosis strains. These barriers reinforcing the need for development of new antimicrobial agents, that ideally should reduce the time of treatment and be active against susceptible and resistant strains. Quinones are compounds found in natural sources and among them, the naphthoquinones show antifungal, antiparasitic, and antimycobacterial activity...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29663670/analogue-synthesis-reveals-decoupling-of-antibiofilm-and-%C3%AE-lactam-potentiation-activities-of-a-lead-2-aminoimidazole-adjuvant-against-mycobacterium-smegmatis
#8
Sara E Martin, Catherine M Nguyen, Randall J Basaraba, Christian Melander
Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro, it expresses phenotypic resistance to antimicrobial drugs. As the in vivo survival of M. tuberculosis following drug treatment is potentially linked to a biofilm-like expression of drug tolerance, it is hypothesized that biofilm dispersion should increase antibiotic susceptibility and reduce the duration of the current antibiotic treatment regimen...
April 16, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29653033/organometallic-conjugates-of-the-drug-sulfadoxine-for-combatting-antimicrobial-resistance
#9
Peter J Sadler, Prinessa Chellan, Vicky Avery, Sandra Duffy, James Triccas, Gayathri Nagalingam, Christina Tam, Luisa Cheng, Jenny Liu, Kirkwood Land, Guy Clarkson, Isolda Romero
Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x-ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 - 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis...
April 13, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29619185/examining-the-role-of-protein-structural-dynamics-in-drug-resistance-in-mycobacterium-tuberculosis
#10
Daniel J Shaw, Rachel E Hill, Niall Simpson, Fouad S Husseini, Kirsty Robb, Gregory M Greetham, Michael Towrie, Anthony W Parker, David Robinson, Jonathan D Hirst, Paul A Hoskisson, Neil T Hunt
Antimicrobial resistance represents a growing global health problem. The emergence of novel resistance mechanisms necessitates the development of alternative approaches to investigate the molecular fundamentals of resistance, leading ultimately to new strategies for counteracting them. To gain deeper insight into antibiotic-target interactions, the binding of the frontline anti-tuberculosis drug isoniazid (INH) to a target enzyme, InhA, from Mycobacterium tuberculosis was studied using ultrafast two-dimensional infrared (2D-IR) spectroscopy and molecular simulations...
December 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29589538/antimicrobial-peptides-for-the-treatment-of-pulmonary-tuberculosis-allies-or-foes
#11
Bruno Rivas-Santiago, Flor Torres-Juarez
Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of world health organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the antimicrobial peptides (AMPs)...
March 27, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29554229/of-testing-and-treatment-implications-of-implementing-new-regimens-for-multidrug-resistant-tuberculosis
#12
David W Dowdy, Grant Theron, Jeffrey A Tornheim, Robin Warren, Emily A Kendall
A novel, shorter-course regimen for treating multidrug-resistant (MDR) tuberculosis was recently recommended by the World Health Organization. However, the most appropriate use of drug susceptibility testing (DST) to support this regimen is less clear. Implementing countries must therefore often choose between using a standardized regimen despite high levels of underlying drug resistance or require more stringent DST prior to treatment initiation. The former carries a high likelihood of exposing patients to de facto monotherapy with a critical drug class (fluoroquinolones), whereas the latter could exclude large groups of patients from their most effective treatment option...
October 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29544082/isolation-and-characterization-of-bacteriophages-from-india-with-lytic-activity-against-mycobacterium-tuberculosis
#13
Urmi Bajpai, Abhishek Kumar Mehta, Kandasamy Eniyan, Avni Sinha, Ankita Ray, Simran Virdi, Shazeb Ahmad, Aridni Shah, Deepanksha Arora, Devyani Marwaha, Gunjan Chauhan, Prarthna Saraswat, Punita Bathla, Ruchi Singh
Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide-spread occurrence of drug resistance among the clinical isolates of Mycobacterium tuberculosis. However, there is not much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using Mycobacterium smegmatis as the bacterial host, where 9 phages also lyse M. tuberculosis H37Rv...
March 15, 2018: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/29531418/integrating-tuberculosis-and-antimicrobial-resistance-control-programmes
#14
Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan
Many low- and middle-income countries facing high levels of antimicrobial resistance, and the associated morbidity from ineffective treatment, also have a high burden of tuberculosis. Over recent decades many countries have developed effective laboratory and information systems for tuberculosis control. In this paper we describe how existing tuberculosis laboratory systems can be expanded to accommodate antimicrobial resistance functions. We show how such expansion in services may benefit tuberculosis case-finding and laboratory capacity through integration of laboratory services...
March 1, 2018: Bulletin of the World Health Organization
https://www.readbyqxmd.com/read/29499834/targeting-bacterial-energetics-to-produce-new-antimicrobials
#15
REVIEW
Kiel Hards, Gregory M Cook
From the war on drug resistance, through cancer biology, even to agricultural and environmental protection: there is a huge demand for rapid and effective solutions to control infections and diseases. The development of small molecule inhibitors was once an accepted "one-size fits all" approach to these varied problems, but persistence and resistance threaten to return society to a pre-antibiotic era. Only five essential cellular targets in bacteria have been developed for the majority of our clinically-relevant antibiotics...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29487047/potential-application-of-digitally-linked-tuberculosis-diagnostics-for-real-time-surveillance-of-drug-resistant-tuberculosis-transmission-validation-and-analysis-of-test-results
#16
Kamela Charmaine Ng, Conor Joseph Meehan, Gabriela Torrea, Léonie Goeminne, Maren Diels, Leen Rigouts, Bouke Catherine de Jong, Emmanuel André
BACKGROUND: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results...
February 27, 2018: JMIR Medical Informatics
https://www.readbyqxmd.com/read/29467300/high-throughput-metabolomic-analysis-predicts-mode-of-action-of-uncharacterized-antimicrobial-compounds
#17
Mattia Zampieri, Balazs Szappanos, Maria Virginia Buchieri, Andrej Trauner, Ilaria Piazza, Paola Picotti, Sébastien Gagneux, Sonia Borrell, Brigitte Gicquel, Joel Lelievre, Balazs Papp, Uwe Sauer
Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29458544/antimicrobial-activity-against-mycobacterium-tuberculosis-under-in-vitro-lipid-rich-dormancy-conditions
#18
Diana Angelica Aguilar-Ayala, Margo Cnockaert, Peter Vandamme, Juan Carlos Palomino, Anandi Martin, Jorge Gonzalez-Y-Merchand
Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model...
March 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29454879/application-of-genetically-encoded-redox-biosensors-to-measure-dynamic-changes-in-the-glutathione-bacillithiol-and-mycothiol-redox-potentials-in-pathogenic-bacteria
#19
REVIEW
Quach Ngoc Tung, Nico Linzner, Vu Van Loi, Haike Antelmann
Gram-negative bacteria utilize glutathione (GSH) as their major LMW thiol. However, most Gram-positive bacteria do not encode enzymes for GSH biosynthesis and produce instead alternative LMW thiols, such as bacillithiol (BSH) and mycothiol (MSH). BSH is utilized by Firmicutes and MSH is the major LMW thiol of Actinomycetes. LMW thiols are required to maintain the reduced state of the cytoplasm, but are also involved in virulence mechanisms in human pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae, Salmonella enterica subsp...
February 15, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29454844/the-epidemiology-of-febrile-illness-in-sub-saharan-africa-implications-for-diagnosis-and-management
#20
REVIEW
M J Maze, Q Bassat, N A Feasey, I Mandomando, P Musicha, J A Crump
BACKGROUND: Fever is among the most common symptoms of people living in Africa, and clinicians are challenged by the similar clinical features of a wide spectrum of potential aetiologies. AIM: To summarize recent studies of fever aetiology in sub-Saharan Africa focusing on causes other than malaria. SOURCES: A narrative literature review by searching the MEDLINE database, and recent conference abstracts. CONTENT: Studies of multiple potential causes of fever are scarce, and for many participants the infecting organism remains unidentified, or multiple co-infecting microorganisms are identified, and establishing causation is challenging...
February 15, 2018: Clinical Microbiology and Infection
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