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multi drug resistant tuberculosis

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https://www.readbyqxmd.com/read/29240876/machine-learning-for-classifying-tuberculosis-drug-resistance-from-dna-sequencing-data
#1
Yang Yang, Katherine E Niehaus, Timothy M Walker, Zamin Iqbal, A Sarah Walker, Daniel J Wilson, Tim E Peto, Derrick W Crook, E Grace Smith, Tingting Zhu, David A Clifton
Motivation: Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Methods: Given the availability of DNA sequencing data from MTB, we developed machine learning models for a cohort of 1839 UK bacterial isolates to classify MTB resistance against eight anti-TB drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, ciprofloxacin, moxifloxacin, ofloxacin, streptomycin) and to classify multi-drug resistance...
December 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29219058/macrophage-targeted-cellular-carriers-for-effective-delivery-of-anti-tubercular-drugs
#2
S Beg, Jaya Agnihotri, Shibhna Singh, Mohammad Wais
Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB).Multi drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe...
December 7, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/29201660/operational-aspects-of-bedaquiline-implementation-in-swaziland-report-from-the-field
#3
D Vambe, T Dlamini, J Furin, C Gracia-Edwards, K Keus, K Kunene, A Shabangu, S N Dlamini, W Sikhondze
Bedaquiline (BDQ) has been recommended by the World Health Organization for the treatment of multi-drug-resistant tuberculosis (MDR-TB) since 2013, but experience using the drug in high-burden, lower-income countries is limited and case studies are needed. Swaziland started using BDQ under national TB programme conditions in 2015 in four pilot sites. As of 1 December 2016, 93 patients had been initiated on BDQ, i.e., 19% of MDR-TB patients treated in the country. Swaziland has developed a systematic and efficient model for BDQ introduction in collaboration with several partners...
September 21, 2017: Public Health Action
https://www.readbyqxmd.com/read/29195272/multivalent-antimicrobial-polymer-nanoparticles-target-mycobacteria-and-gram-negative-bacteria-by-distinct-mechanisms
#4
Sarah-Jane Richards, Klea Isulfi, Laura E Wilkins, Julia Lipecki, Elizabeth Fullam, Matthew I Gibson
Due to the emergence of antimicrobial resistance to traditional small molecule drugs, cationic antimicrobial polymers are appealing targets. Mycobacterium tuberculosis is a particular problem, with multi- and total drug resistance spreading and more than a billion latent infections globally. This study reports nanoparticles bearing variable densities of poly(dimethylaminoethyl methacrylate) and the unexpected and distinct mechanisms of action this multivalent presentation imparts against Escherichia coli verses Mycobacterium smegmatis (model of M...
December 1, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29188776/metal-complexes-of-isonicotinylhydrazide-and-their-antitubercular-activity
#5
Mohsin Ali, Mansoor Ahmed, Saleem Hafiz, Mustafa Kamal, Majid Mumtaz, Muhammad Hanif, Khalid Mohammed Khan
The development and spreading of Multi Drug Resistant TB strains is hampering endeavours for the control and administration of tuberculosis (TB). The expansion episodes of multi-medication safe strains of Mycobacterium tuberculosis against first and second line antituberculosis drugs on one side and the unfavourable effects of these drugs on the other side has led the enthusiasm of researcher towards the synthesis of metal complexes of various medication. This approach is born with the expectation of finding new antituberculous operators without or least reactions as well as being active against the resistant strains of Mycobacterium tuberculosis...
November 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29186408/a-significant-therapeutic-effect-of-immunoglobulins-administered-alone-or-in-combination-with-conventional-chemotherapy-in-experimental-pulmonary-tuberculosis-caused-by-drug-sensitive-or-drug-resistant-strains
#6
Nesty Olivares, Yadira Rodriguez, Zyanya Lucia Zatarain-Barron, Brenda Marquina, Dulce Mata-Espinosa, Jorge Barrios-Payán, Cristina Parada, Bárbara Moguel, Clara Espitia Pinzón, Iris Estrada, Rogelio Hernandez-Pando
The recommended chemotherapy for drug sensitive tuberculosis (TB) consists of four different antibiotics administrated for 6-months. This long treatment leads to significant compliance problems and consequently to recrudescence of the disease and to the development of multi drug resistant strains (MDR). Thus, new alternatives are needed to shorten or simplify the treatment of TB. Antibodies have therapeutic effects in animal models of TB, so their use as adjuvants in drug sensitive and MDR TB is an interesting alternative...
November 23, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/29180526/on-the-antibacterial-and-sterilizing-effect-of-benzylpenicillin-in-tuberculosis
#7
Devyani Deshpande, Shashikant Srivastava, Paula Bendet, Katherine R Martin, Kayle N Cirrincione, Pooi S Lee, Jotam G Pasipanodya, Keertan Dheda, Tawanda Gumbo
The modern chemotherapy era started with Fleming's discovery of benzylpenicillin. He demonstrated that benzylpenicillin did not kill Mycobacterium tuberculosis (Mtb) Here, we found that >64 mg/L of static benzylpenicillin concentrations killed 1.16-1.43 log10 CFU/mL below starting inoculum of extracellular and intracellular Mtb over 7 days. When we added the β-lactamase-inhibitor avibactam, benzylpenicillin maximal kill (Emax) of either extracellular log-phase growth Mtb was 6.80±0.45 log10 CFU/mL at an EC50 of 15...
November 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29151652/antimicrobial-efficacy-of-synthetic-pyranochromenones-and-coumarinyloxy-acetamides
#8
Abhishek K Singh, Suchita Prasad, Bipul Kumar, Shiv Kumar, Amitesh Anand, Shashank S Kamble, Sunil K Sharma, Hemant K Gautam
Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S...
December 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/29135397/electrolytes-imbalance-caused-by-amikacin-in-patients-receiving-multi-drug-resistance-tuberculosis-treatment-at-hazara-region-kpk-pakistan
#9
Faheem Jan, Mukhtiar Hassan, Naveed Muhammad, Shahid Wali, Hafiz Sajid Akbar, Qazi Mashhood Atta, Farzana Gul
Introduction: Multi drug resistance-tuberculosis (MDR-TB) is considered amongst one of the fatal medical and public health issue. Greater frequency of adverse reactions has been observed using 2nd line antituberculosis drugs, which rises the rate of morbidity. Hypokalemia and hyponatremia are common in patients receiving MDR-TB treatment. Materials and Methods: This study was aimed to assess the effect of amikacin as multidrug resistance tuberculosis treatment on serum sodium and potassium level...
September 2017: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/29133554/what-is-resistance-impact-of-phenotypic-versus-molecular-drug-resistance-testing-on-multi-and-extensively-drug-resistant-tuberculosis-therapy
#10
Jan Heyckendorf, Sönke Andres, Claudio U Köser, Ioana D Olaru, Thomas Schön, Erik Sturegård, Patrick Beckert, Viola Schleusener, Thomas A Kohl, Doris Hillemann, Danesh Moradigaravand, Julian Parkhill, Sharon J Peacock, Stefan Niemann, Christoph Lange, Matthias Merker
Rapid and accurate drug-susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using BACTEC 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs.Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs: Hain GenoType MTBDRplus 2.0 and MTBDRsl 2...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29129474/-screening-program-for-tuberculosis-among-international-exchange-students-in-the-department-of-is%C3%A3-re
#11
M-V Albahary, F Blanc-Jouvan, C Recule, C Dubey, P Pavese
INTRODUCTION: France is a low-incidence country for tuberculosis (TB). Consequently screening is focused on high-risk populations, in particular migrants. The aim of this study was to evaluate the epidemiology of TB among international exchange students in the Department of Isère and the screening programs used. METHODS: We carried out an organizational audit based on interviews with physicians involved in the management of TB in Isère. We conducted a retrospective descriptive study based on a case series of foreign students treated for TB from 2003 to 2013 inclusively...
November 9, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/29124005/massive-hemoptysis-from-rasmussen-s-aneurysm-in-active-pulmonary-tuberculosis-a-case-report-of-successful-treatment-with-bronchial-artery-embolization
#12
K V Rajamannar, Hemanth Kilaru, Srujana Aravelly, Ananta Ram Gudipati, Satish Chandra Kilaru
Rasmussen's aneurysm, a very rare complication of active pulmonary tuberculosis (TB), is a pulmonary artery aneurysm adjacent to or within a tuberculous cavity. It may lead to rupture and life threatening massive hemoptysis, an uncommon but challenging medico-surgical emergency. This complication warrants attention in view of the resurgence of tuberculosis and increasing occurrence of multi-drug resistant TB, especially in resource-poor, high-TB burden countries like India. We present a case of an elderly man who presented to the emergency room with low-grade fever, cough and hemoptysis...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29116641/mathematical-models-for-the-epidemiology-and-evolution-of-mycobacterium-tuberculosis
#13
Jūlija Pečerska, James Wood, Mark M Tanaka, Tanja Stadler
This chapter reviews the use of mathematical and computational models to facilitate understanding of the epidemiology and evolution of Mycobacterium tuberculosis. First, we introduce general epidemiological models, and describe their use with respect to epidemiological dynamics of a single strain and of multiple strains of M. tuberculosis. In particular, we discuss multi-strain models that include drug sensitivity and drug resistance. Second, we describe models for the evolution of M. tuberculosis within and between hosts, and how the resulting diversity of strains can be assessed by considering the evolutionary relationships among different strains...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29068470/aspartate-%C3%AE-semialdeyhyde-dehydrogenase-as-a-potential-therapeutic-target-of-mycobacterium-tuberculosis-h37rv-evidence-from-in-silico-elementary-mode-analysis-of-biological-network-model
#14
Saif Khan, Pallavi Somvanshi, Tulika Bhardwaj, Raju K Mandal, Sajad A Dar, Mohd Wahid, Arshad Jawed, Mohtashim Lohani, Mahvish Khan, Mohammed Y Areeshi, Shafiul Haque
The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets [aspartate-β-semialdeyhde dehydrogenase (ASD), dihydrodipicolinate reductase and diaminopimelate decarboxylase] based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways...
October 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29061956/oxycodone-resistance-due-to-rifampin-use-in-an-osteosarcoma-patient-with-tuberculosis
#15
Akio Sakamoto, Manato Yamashita, Yuta Hori, Takeshi Okamoto, Atsushi Shimizu, Shuichi Matsuda
BACKGROUND Oxycodone is a semisynthetic opioid receptor agonist, and is frequently used for pain control in patients with cancer. Most oxycodone is metabolized by N-demethylation to noroxycodone by CYP3A. Rifampin is a strong inducer of several drug-metabolizing enzymes, including CYP3A. Hence, rifampin-induced CYP3A activity may decrease the effect of oxycodone. CASE REPORT Osteosarcoma is a highly aggressive primary bone tumor of childhood and adolescence. Here, we report a 30-year-old male with osteosarcoma of the femur with lung metastases in the upper lobe...
October 24, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29061336/management-of-mdr-tb-in-hiv-co-infected-patients-in-eastern-europe-results-from-the-tb-hiv-study
#16
A M W Efsen, A Schultze, R F Miller, A Panteleev, A Skrahin, D N Podlekareva, J M Miro, E Girardi, H Furrer, M H Losso, J Toibaro, J A Caylà, A Mocroft, J D Lundgren, F A Post, O Kirk
OBJECTIVES: Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. METHODS: In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). RESULTS: A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB...
October 20, 2017: Journal of Infection
https://www.readbyqxmd.com/read/29050761/mechanisms-of-resistance-against-nitd-916-a-direct-inhibitor-of-mycobacterium-tuberculosis-inha
#17
Matthew B McNeil, Devon Dennison, Catherine Shelton, Lindsay Flint, Aaron Korkegian, Tanya Parish
Isoniazid inhibits Mycobacterium tuberculosis InhA and is a key component of drug regimens that treat tuberculosis. However, the high rate of resistance against isoniazid is a contributing factor to the emergence of multi-drug resistance strains of M. tuberculosis. The 4-hydroxy-2-pyridine NITD-916 is a direct inhibitor of M. tuberculosis InhA that has comparable efficacy to isoniazid in mouse models of TB infection but a lower frequency of resistance. To characterize resistance mechanisms against NITD-916 we isolated resistant mutants in H37Rv (Euro-American lineage) and HN878 (East-Asian lineage) strains of M...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29050755/applied-multiplex-allele-specific-pcr-to-detect-second-line-drug-resistance-among-multidrug-resistant-tuberculosis-in-china
#18
Ya-Ping Liang, Yan Chen, Tong-Yang Xiao, Qiang Xia, Hai-Can Liu, Xiu-Qin Zhao, Chun-Yan Zeng, Li-Li Zhao, Kang-Lin Wan
Rapid detection of resistance to the second-line drugs is essential for early initiation of appropriate anti-tubercular treatment regimen among multi-drug tuberculosis (MDR-TB). In this study, we applied a multiplex allele-specific PCR (MAS-PCR) to identify the mutations on codons 90 and 94 of gyrA and nucleotide 1401 of rrs for detecting ofloxacin (OFX) and kanamycin (KAN) resistance in 139 MDR-TB isolates from China. Using the traditional phenotypic method as the reference, MAS-PCR detected resistance to OFX and KAN with sensitivities of 67...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29042210/the-physicochemical-basis-of-clofazimine-induced-skin-pigmentation
#19
Mikhail D Murashov, Vernon LaLone, Phillip M Rzeczycki, Rahul K Keswani, Gi S Yoon, Sudha Sud, Walajapet Rajeswaran, Scott Larsen, Kathleen A Stringer, Gus R Rosania
Clofazimine is a weakly basic, FDA-approved antibiotic recommended by the World Health Organization to treat leprosy and multi-drug-resistant tuberculosis. Upon prolonged treatment, clofazimine extensively bioaccumulates and precipitates throughout the organism, forming crystal-like drug inclusions (CLDIs). Because of the drug's red color, it is widely believed that clofazimine bioaccumulation results in skin pigmentation, its most common side effect. To test whether clofazimine-induced skin pigmentation is due to CLDI formation, we synthesized a closely related clofazimine analog that does not precipitate under physiological pH and chloride conditions that are required for CLDI formation...
October 14, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29031637/molecular-epidemiology-of-multi-and-extensively-drug-resistant-mycobacterium-tuberculosis-in-ireland-2001-2014
#20
E Roycroft, R F O'Toole, M M Fitzgibbon, L Montgomery, M O'Meara, P Downes, S Jackson, J O'Donnell, I F Laurenson, A M McLaughlin, J Keane, T R Rogers
OBJECTIVES: The primary objective of this work was to examine the acquisition and spread of multi-drug resistant (MDR) tuberculosis (TB) in Ireland. METHODS: All available Mycobacterium tuberculosis complex (MTBC) isolates (n = 42), from MDR-TB cases diagnosed in Ireland between 2001 and 2014, were analysed using phenotypic drug-susceptibility testing, Mycobacterial-Interspersed-Repetitive-Units Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping, and whole-genome sequencing (WGS)...
October 12, 2017: Journal of Infection
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