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anti tuberculosis drugs

Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Ramani Baddam, Narender Kumar, Lothar H Wieler, Aditya Kumar Lankapalli, Niyaz Ahmed, Sharon J Peacock, Torsten Semmler
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, resistance to which occurs primarily due to mutations in pncA (Rv2043c) that encodes the pyrazinamidase enzyme responsible for conversion of pro-drug PZA into its active form. Previous studies have reported numerous resistance-conferring mutations distributed across the entire length of pncA without any hotspot regions. As different lineages of Mycobacterium tuberculosis display a strong geographic association, we sought to understand whether the genetic background influenced the distribution of mutations in pncA...
March 15, 2018: Scientific Reports
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
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 amongst the clinical isolates of M. tuberculosis. However, there isn't much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using M. smegmatis as the bacterial host where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophage (PDRPv)...
March 15, 2018: Canadian Journal of Microbiology
Nikunjkumar Patel, Oliver Hatley, Alexander Berg, Klaus Romero, Barbara Wisniowska, Debra Hanna, David Hermann, Sebastian Polak
Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis...
March 14, 2018: AAPS Journal
Ye-Jin Lee, Sung Koo Han, Ju Hee Park, Jung Kyu Lee, Deog Keom Kim, Hee Soon Chung, Eun Young Heo
Background/Aims: Patients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM. Methods: This retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012...
March 16, 2018: Korean Journal of Internal Medicine
Vasyl Kovalishyn, Julie Grouleff, Ivan Semenyuta, Vitaliy O Sinenko, Sergiy R Slivchuk, Diana Hodyna, Volodymyr Brovarets, Volodymyr Blagodatny, Gennady Poda, Igor V Tetko, Larysa Metelytsia
The problem of designing new anti-tubercular drugs against multiple-drug-resistant tuberculosis (MDR-TB) was addressed using advanced machine learning methods. Since there are only few published measurements against MDR-TB, we collected a large literature dataset and developed models against the non-resistant H37Rv strain. The predictive accuracy of these models had a coefficient of determination q2 = 0.7-0.8 (regression models), and balanced accuracies of about 80% (classification models) with cross-validation and independent test sets...
March 14, 2018: Chemical Biology & Drug Design
Wolfgang Miehsler, Clemens Dejaco, Hans-Peter Gröchenig, Harry Fuchssteiner, Christoph Högenauer, Lili Kazemi-Shirazi, Harald Maier, Andreas Mayer, Alexander Moschen, Walter Reinisch, Wolfgang Petritsch, Reingard Platzer, Pius Steiner, Herbert Tilg, Harald Vogelsang, Heimo Wenzl, Gottfried Novacek
Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i...
March 2018: Zeitschrift Für Gastroenterologie
Andrew I Rutherford, Eunice Patarata, Sujith Subesinghe, Kimme L Hyrich, James B Galloway
Objectives: This analysis set out to estimate the risk of opportunistic infection (OI) among patients with RA by biologic class. Methods: The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis is a prospective observational cohort study established to evaluate safety of biologic therapies. The population included adults commencing biologic therapy for RA. The primary outcome was any serious OI excluding tuberculosis (TB). Event rates were compared across biologic classes using Cox proportional hazards with adjustment for potential confounders identified a priori...
February 26, 2018: Rheumatology
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
Yeo Jun Yun, Jong Seok Lee, Je Chul Yoo, Eunjin Cho, Dahee Park, Yoon Hoh Kook, Keun Hwa Lee
BACKGROUND: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea...
March 7, 2018: Tuberculosis and Respiratory Diseases
Basanth Babu Eedara, Bhamini Rangnekar, Colin Doyle, Alex Cavallaro, Shyamal C Das
Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid L-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% L-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced...
March 7, 2018: International Journal of Pharmaceutics
Christine Sekaggya-Wiltshire, Mohammed Lamorde, Agnes N Kiragga, Kelly E Dooley, Moses R Kamya, Andrew Kambugu, Jan Fehr, Yukari C Manabe, Barbara Castelnuovo
Tuberculosis (TB) is a major public health problem. Many countries still fall below the minimum World Health Organization (WHO) TB treatment target success rate. There is conflicting evidence about whether concentrations of anti-tuberculosis drugs given at standard doses have an effect on treatment outcomes. The current data correlating anti-TB drug concentrations and treatment outcome is limited. This article summarized the existing literature and their utility in evaluating the association between each anti-TB drug's concentrations using current target concentrations and treatment outcomes in patients with pulmonary tuberculosis receiving standard WHO-recommended dosing...
January 2018: Tuberculosis
Sunil Kumar, Rukmankesh Mehra, Sumit Sharma, Naveen Prakash Bokolia, Diksha Raina, Amit Nargotra, Parvinder Pal Singh, Inshad Ali Khan
A limited number of anti-tuberculosis drug candidates with novel mode of action have entered clinical trials in recent years. ATP synthase is one such validated drug target which has yielded a drug recently. The aim of this study was to identify the novel chemical scaffolds targeting the Mycobacterium tuberculosis (M. tuberculosis) ATP synthase. In this study, inverted membrane vesicles of Mycobacterium smegmatis were prepared to establish luciferin based ATP estimation assay. This assay was used to screen 700 compounds which were earlier found to be active on the whole cell of M...
January 2018: Tuberculosis
Matthew W Marney, Robert P Metzger, David Hecht, Faramarz Valafar
WHO reported 10.4 million new tuberculosis (TB) cases and 1.8 million deaths in 2015, making M. tuberculosis the most successful human pathogen with highest mortality among infectious diseases [1,2]. Drug-resistant TB is a major threat to global TB control [2,3]. Recently Torres et al. [4] identified 14 novel substitutions in M. tuberculosis-KatG (the enzyme associated with resistance to isoniazid-an important first-line anti-TB drug) and demonstrated that 12 of the 14 can cause INH-resistance in M. smegmatis...
January 2018: Tuberculosis
Rohit Shukla, Harish Shukla, Timir Tripathi
Mycobacterium tuberculosis isocitrate lyase (MtbICL) is a crucial enzyme of the glyoxylate cycle and is a validated anti-tuberculosis drug target. Structurally distant, non-active site mutation (H46A) in MtbICL has been found to cause loss of enzyme activity. The aim of the present work was to explore the structural alterations induced by H46A mutation that caused the loss of enzyme activity. The structural and dynamic consequences of H46A mutation were studied using multiple computational methods such as docking, molecular dynamics simulation and residue interaction network analysis (RIN)...
January 2018: Tuberculosis
Sebastian Polak, Klaus Romero, Alexander Berg, Nikunjkumar Patel, Masoud Jamei, David Hermann, Debra Hanna
Cardiotoxicity is among the top drug safety concerns, and is of specific interest in tuberculosis, where this is a known or potential adverse event of current and emerging treatment regimens. As there is a need for a tool, beyond the QT interval, to quantify cardiotoxicity early in drug development, an empirical decision tree based classifier was developed to predict the risk of Torsades de pointes (TdP). The cardiac risk algorithm was developed using pseudo-electrocardiogram (ECG) outputs derived from cardiac myocyte electromechanical model simulations of increasing concentrations of 96 reference compounds which represented a range of clinical TdP risk...
March 8, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Mathieu Bastard, Elisabeth Sanchez-Padilla, Philipp du Cros, Atadjan Karimovich Khamraev, Nargiza Parpieva, Mirzagaleg Tillyashaykov, Armen Hayrapetyan, Kamene Kimenye, Shazina Khurkhumal, Themba Dlamini, Santiago Fadul Perez, Alex Telnov, Cathy Hewison, Francis Varaine, Maryline Bonnet
BACKGROUND: The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. METHODS: We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan...
2018: PloS One
Tapaswini Nayak, Lingaraja Jena, Pranita Waghmare, Bhaskar C Harinath
Background: The Mycobacterium tuberculosis (MTB) uridine diphosphogalactofuranose (UDP)-galactopyranose mutase (UGM) is an essential flavoenzyme for mycobacterial viability and an important component of cell wall. It catalyzes the interconversion of UDP-galactopyranose into UDP-galactofuranose, a key building block for cell wall construction, essential for linking the peptidoglycan and mycolic acid cell wall layers in MTB through a 2-keto intermediate. Further, as this enzyme is not present in humans, it is an excellent therapeutic target for MTB...
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
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