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multi drug resistant tuberculosis

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https://www.readbyqxmd.com/read/28630205/the-impact-of-gyrb-and-eis-mutations-in-improving-second-line-drug-resistance-detection-among-mycobacterium-tuberculosis-isolates-from-georgia
#1
N Bablishvili, N Tukvadze, E Shashkina, B Mathema, N R Gandhi, H M Blumberg, R R Kempker
SETTING: The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB).OBJECTIVE: To evaluate whether the detection of mutations in gyrB and eis genes increased the sensitivity of detecting phenotypic resistance to ofloxacin and kanamycin or capreomycin as compared to use of the first generation MTBDRsl assay alone which evaluates for mutations in gyrA and rrs genes.DESIGN: A retrospective study of storedMycobacterium tuberculosis isolates. All isolates underwent DNA sequencing of resistance determining regions...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630193/pyrazinamide-susceptibility-and-pnca-mutation-profile-of-mycobacterium-tuberculosis-among-multi-drug-resistant-tuberculosis-patients-in-bangladesh
#2
Arfatur Rahman, Sara Sabrina Ferdous, Shahriar Ahmed, S M Mazidur Rahman, Mohammad Khaja Mafij Uddin, Suporn Pholwat, Jean Gratz, Eric Houpt, Sayera Banu
Pyrazinamide (PZA) is a front line anti-tuberculosis (anti-TB) drug used in both first and second line treatment regimen. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed leading to the scarcity of data. Bangladesh is both a high TB and multi-drug resistant (MDR-TB) burden country but to our knowledge the published data on PZA susceptibility is limited, especially among MDR-TB patients. We aimed to analyze the PZA susceptibility pattern of Mycobacterium tuberculosis (MTB) isolates from MDR-TB patients and to correlate pncA mutation with PZA resistance in Bangladesh...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28620844/comparison-of-the-characteristics-of-mycobacterium-tuberculosis-isolates-from-sputum-and-lung-lesions-in-chronic-tuberculosis-patients
#3
M-S Hong, Y Kim, E-J Cho, J-S Lee, H-K Kwak, J-H Kim, C-T Kim, J-S Cho, S-K Park, D Jeon, Y-I Choi, H Lee, S-Y Eum
Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB...
June 15, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28611374/efficacy-and-safety-of-mycobacterium-indicus-pranii-as-an-adjunct-therapy-in-category-ii-pulmonary-tuberculosis-in-a-randomized-trial
#4
Surendra K Sharma, Kiran Katoch, Rohit Sarin, Raman Balambal, Nirmal Kumar Jain, Naresh Patel, Kolluri J R Murthy, Neeta Singla, P K Saha, Ashwani Khanna, Urvashi Singh, Sanjiv Kumar, A Sengupta, J N Banavaliker, D S Chauhan, Shailendra Sachan, Mohammad Wasim, Sanjay Tripathi, Nilesh Dutt, Nitin Jain, Nalin Joshi, Sita Ram Raju Penmesta, Sumanlatha Gaddam, Sanjay Gupta, Bakulesh Khamar, Bindu Dey, Dipendra K Mitra, Sunil K Arora, Sangeeta Bhaskar, Rajni Rani
Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 10(8) bacilli or placebo once in 2 weeks for 2 months...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610784/molecular-investigation-of-active-binding-site-of-isoniazid-inh-and-insight-into-resistance-mechanism-of-s315t-mtkatg-in-mycobacterium-tuberculosis
#5
Gaurava Srivastava, Shubhandra Tripathi, Akhil Kumar, Ashok Sharma
Multi drug resistant tuberculosis is a major threat for mankind. Resistance against Isoniazid (INH), targeting MtKatG protein, is one of the most commonly occurring resistances in MDR TB strains. S315T-MtKatG mutation is widely reported for INH resistance. Despite having knowledge about the mechanism of INH, exact binding site of INH to MtKatG is still uncertain and proposed to have three presumable binding sites (site-1, site-2, and site-3). In the current study docking, molecular dynamics simulation, binding free energy estimation, principal component analysis and free energy landscape analysis were performed to get molecular level details of INH binding site on MtKatG, and to probe the effect of S315T mutation on INH binding...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-optimising-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#6
Maxwell T Chirehwa, Helen McIlleron, Roxana Rustomjee, Thuli Mthiyane, Philip Onyebujoh, Peter Smith, Paolo Denti
Pyrazinamide is used in the treatment of tuberculosis(TB) because its sterilising effect against tubercle bacilli allows treatment shortening. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multi-drug resistant tuberculosis(MDR-TB)...
June 12, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28595939/role-of-second-line-injectable-antituberculosis-drugs-in-the-treatment-of-mdr-xdr-tuberculosis
#7
Fanny Quenard, Pierre Edouard Fournier, Michel Drancourt, Philippe Brouqui
Second-line injectable antituberculosis drugs (aminoglycosides and capreomycin) are the main drugs used in the management of resistant tuberculosis. Their preserved efficacy in the case of multi-drug-resistant bacillus is counterbalanced by frequent adverse events. Adverse events are linked to the drugs themselves and to the recommended 8-month period of parenteral administration. In numerous countries facing a high incidence of multi-drug-resistant tuberculosis, treatment is administered by intramuscular injection...
June 5, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28594940/the-introduction-of-mesenchymal-stromal-cells-induces-different-immunological-responses-in-the-lungs-of-healthy-and-m-tuberculosis-infected-mice
#8
Tatiana Nenasheva, Alexander Nikolaev, Daniar Diykanov, Anna Sukhanova, Evgenii Tcyganov, Alexander Panteleev, Irina Bocharova, Yana Serdyuk, Leonid Nezlin, Tatiana Radaeva, Nikolai Adrianov, Yuri Rubtsov, Irina Lyadova
Mesenchymal stromal cells (MSC) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. It was suggested recently that MSC injections can be used to treat multi-drug resistant tuberculosis (TB). However, MSC trafficking and immunomodulatory effects of MSC injections during Mycobacterium tuberculosis (Mtb) infection have not been studied. To address this issue we have analyzed MSC distribution in tissues and local immunological effects of MSC injections in Mtb infected and uninfected mice...
2017: PloS One
https://www.readbyqxmd.com/read/28586348/primary-multidrug-resistant-tuberculosis-versus-drug-sensitive-tuberculosis-in-non-hiv-infected-patients-comparisons-of-ct-findings
#9
Duo Li, Wei He, Budong Chen, Pingxin Lv
BACKGROUND: Multidrug-resistant tuberculosis has emerged as a global threat. The aim of this work was to compare the CT findings of primary multidrug-resistant tuberculosis and drug-sensitive tuberculosis in non-AIDS adults. MATERIAL AND METHODS: From January 2012 to February 2016, 89 patients with primary multidrug-resistant tuberculosis were retrospectively reviewed, and 89 consecutive drug sensitive TB patients with no history of anti-tuberculous chemotherapy from January 2014 to November 2014 were enrolled as control group...
2017: PloS One
https://www.readbyqxmd.com/read/28584788/clinical-implications-of-new-drugs-and-regimens-for-the-treatment-of-drug-resistant-tuberculosis
#10
REVIEW
Yong-Soo Kwon
The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB...
May 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28571806/bioinformatics-approach-to-prioritize-known-drugs-towards-repurposing-for-tuberculosis
#11
Sridharan Brindha, Savariar Vincent, Devadasan Velmurugan, Dhanabalan Ananthakrishnan, Jagadish Chandrabose Sundaramurthi, John Joel Gnanadoss
New drugs are urgently needed to cure tuberculosis (TB) in a short period of time without causing any adverse effects since currently used drugs for the treatment of multi drug-resistant TB cause several adverse effects with poor success rate. Therefore, we aimed to prioritize known drugs towards repurposing for TB by employing bioinformatics approach in the present study. A total of 1554 FDA approved drugs were obtained from DrugBank. Serine/threonine-protein kinase, pknB (Rv0014c) of Mycobacterium tuberculosis (Mtb) was selected as the drug target since it involves in several vital functions of the Mtb...
June 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28558838/towards-understanding-the-drivers-of-policy-change-a-case-study-of-infection-control-policies-for-multi-drug-resistant-tuberculosis-in-south-africa
#12
Trust Saidi, Faatiema Salie, Tania S Douglas
BACKGROUND: Explaining policy change is one of the central tasks of contemporary policy analysis. In this article, we examine the changes in infection control policies for multi-drug resistant tuberculosis (MDR-TB) in South Africa from the time the country made the transition to democracy in 1994, until 2015. We focus on MDR-TB infection control and refer to decentralised management as a form of infection control. Using Kingdon's theoretical framework of policy streams, we explore the temporal ordering of policy framework changes...
May 30, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28549496/mutual-impact-of-diabetes-mellitus-and-tuberculosis-in-china
#13
Jun Cheng, Hui Zhang, Yan Lin Zhao, Li Xia Wang, Ming Ting Chen
China has a double burden of diabetes mellitus and tuberculosis, and many studies have been carried out on the mutual impact of these two diseases. This paper systematically reviewed studies conducted in China covering the mutual impact of epidemics of diabetes and tuberculosis, the impact of diabetes on multi-drug resistant tuberculosis and on the tuberculosis clinical manifestation and treatment outcome, the yields of bi-directional screening, and economic evaluation for tuberculosis screening among diabetes patients...
May 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28544095/phenotypic-assays-for-mycobacterium-tuberculosis-infection
#14
Ok-Ryul Song, Nathalie Deboosere, Vincent Delorme, Christophe J Queval, Gaspard Deloison, Elisabeth Werkmeister, Frank Lafont, Alain Baulard, Raffaella Iantomasi, Priscille Brodin
Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB...
May 19, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28533124/the-novel-gene-mtb192-is-a-candidate-marker-for-the-detection-of-multidrug-resistant-mycobacterium-tuberculosis-strains
#15
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/28496433/interplay-between-mutations-and-efflux-in-drug-resistant-clinical-isolates-of-mycobacterium-tuberculosis
#16
Diana Machado, Tatiane S Coelho, João Perdigão, Catarina Pereira, Isabel Couto, Isabel Portugal, Raquel De Abreu Maschmann, Daniela F Ramos, Andrea von Groll, Maria L R Rossetti, Pedro A Silva, Miguel Viveiros
Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28487681/etha-r-independent-killing-of-mycobacterium-tuberculosis-by-ethionamide
#17
Michelle L T Ang, Siti Z Zainul Rahim, Paola Florez de Sessions, Wenwei Lin, Vanessa Koh, Kevin Pethe, Martin L Hibberd, Sylvie Alonso
Ethionamide (ETH) is part of the drug arsenal available to treat multi-drug resistant tuberculosis. The current paradigm of this pro-drug activation involves the mycobacterial enzyme EthA and the transcriptional repressor, EthR. However, several lines of evidence suggest the involvement of additional players. The ethA/R locus was deleted in Mycobacterium bovis BCG and three Mycobacterium tuberculosis (MTB) strains. While complete resistance to ETH was observed with BCG ethA/R KO, drug susceptibility and dose-dependent killing were retained in the ethA/R KO MTB mutants, suggesting the existence of an alternative pathway of ETH bio-activation in MTB...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28472053/recurrent-tuberculosis-and-associated-factors-a-five-year-countrywide-study-in-uzbekistan
#18
Jamshid Gadoev, Damin Asadov, Anthony D Harries, Nargiza Parpieva, Katie Tayler-Smith, Petros Isaakidis, Engy Ali, Sven Gudmund Hinderaker, Gozalov Ogtay, Andrew Ramsay, Avazbek Jalolov, Masoud Dara
BACKGROUND: In Uzbekistan, despite stable and relatively high tuberculosis treatment success rates, relatively high rates of recurrent tuberculosis have recently been reported. Recurrent tuberculosis is when a patient who was treated for pulmonary tuberculosis and cured, later develops the disease again. This requires closer analysis to identify possible causes and recommend interventions to improve the situation. Using countrywide data, this study aimed to analyse trends in recurrent tuberculosis cases and describe their associations with socio-demographic and clinical factors...
2017: PloS One
https://www.readbyqxmd.com/read/28454646/activity-of-rifampicin-and-linezolid-combination-in-mycobacterium-tuberculosis
#19
Flaviane Granero Maltempe, Katiany Rizzieri Caleffi-Ferracioli, Renata Claro Ribeiro do Amaral, Fernanda de Oliveira Demitto, Vera Lúcia Dias Siqueira, Regiane Bertin de Lima Scodro, Mário Hiroyuki Hirata, Fernando Rogério Pavan, Rosilene Fressatti Cardoso
BACKGROUND: Linezolid (LZD) is not commonly used for treating tuberculosis (TB), but in some patients with drug-resistant TB it is being used. However, the in vitro LZD activity, in combination with rifampicin (RIF) against Mycobacterium tuberculosis has not been fully elucidated. AIMS: The aim of this study was to evaluate the in vitro activity of RIF/LZD combination against M. tuberculosis clinical isolates. MATERIALS AND METHODS: The activity of the RIF/LZD combination was firstly determined in M...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28451184/combatting-amr-photoactivatable-ruthenium-ii-isoniazid-complex-exhibits-rapid-selective-antimycobacterial-activity
#20
Nichola A Smith, Pingyu Zhang, Simon E Greenough, Michael D Horbury, Guy J Clarkson, Daniel McFeely, Abraha Habtemariam, Luca Salassa, Vasilios G Stavros, Christopher G Dowson, Peter J Sadler
The novel photoactive ruthenium(ii) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1·2PF6, INH = isoniazid) was designed to incorporate the anti-tuberculosis drug, isoniazid, that could be released from the Ru(ii) cage by photoactivation with visible light. In aqueous solution, 1 rapidly released two equivalents of isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2](2+) upon irradiation with 465 nm blue light. We screened for activity against bacteria containing the three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and multi-colored LED multi-well arrays...
January 1, 2017: Chemical Science
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