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https://www.readbyqxmd.com/read/28105975/simultaneous-determination-of-first-line-4-fdc-antituberculosis-drugs-by-uhplc-uv-and-hplc-uv-a-comparative-study
#1
Pedro H C Franco, Paula R Chellini, Marcone A L Oliveira, Gerson A Pianetti
Tuberculosis is the second most deadly infectiousdisease, surpassed only by HIV/AIDS, and hasresulted in over 1 billion deaths in the last200 years. The World Health Organization estimatesthat in 2014, 9.6 million people were infected bythis disease and 1.5 million had died. First-choicetreatment consists of fixed-dose combinationtablets containing rifampicin, isoniazid,pyrazinamide, and ethambutol hydrochloride(4-FDC). There are pharmacopeial protocolsavailable to test 4-FDC, but they are prolonged,two-step methods...
January 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28100438/high-dose-rifampicin-moxifloxacin-and-sq109-for-treating-tuberculosis-a-multi-arm-multi-stage-randomised-controlled-trial
#2
Martin J Boeree, Norbert Heinrich, Rob Aarnoutse, Andreas H Diacon, Rodney Dawson, Sunita Rehal, Gibson S Kibiki, Gavin Churchyard, Ian Sanne, Nyanda E Ntinginya, Lilian T Minja, Robert D Hunt, Salome Charalambous, Madeleine Hanekom, Hadija H Semvua, Stellah G Mpagama, Christina Manyama, Bariki Mtafya, Klaus Reither, Robert S Wallis, Amour Venter, Kim Narunsky, Anka Mekota, Sonja Henne, Angela Colbers, Georgette Plemper van Balen, Stephen H Gillespie, Patrick P J Phillips, Michael Hoelscher
BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol)...
January 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28081036/one-year-mortality-of-hiv-positive-patients-treated-for-rifampicin-and-isoniazid-susceptible-tuberculosis-in-eastern-europe-western-europe-and-latin-america
#3
(no author information available yet)
OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those in Western Europe or Latin America. METHODS: One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study...
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28063906/pyrazinamide-induced-hepatotoxicity-is-alleviated-by-4-pba-via-inhibition-of-the-perk-eif2%C3%AE-atf4-chop-pathway
#4
Hong-Li Guo, Hozeifa M Hassan, Ping-Ping Ding, Shao-Jie Wang, Xi Chen, Tao Wang, Li-Xin Sun, Lu-Yong Zhang, Zhen-Zhou Jiang
Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. In this study, we describe the role of ER stress in PZA induced hepatotoxicity in vivo and in vitro. We found that PZA induces apoptosis in HepG2 cells, and causes liver damage in rats, characterized by increased serum ALT, AST and TBA levels...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28060046/serious-adverse-reactions-from-anti-tuberculosis-drugs-among-599-children-hospitalized-for-tuberculosis
#5
Yiyuan Li, Yu Zhu, Qin Zhong, Xiaojun Zhang, Min Shu, Chaomin Wan
BACKGROUNDS: The purpose of the study was to summarize the clinical characteristics of serious adverse reactions (ARs) related to anti-tuberculosis (TB) drugs in children hospitalized for TB. A comprehensive understanding of these drug-related ARs may serve to improve patient prognosis. METHOD: Inpatients diagnosed with TB from 2008 to 2013 were enrolled retrospectively. The patients' demographics, diagnosis and ARs were recorded and analyzed for comprehensive evaluation...
January 3, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28043638/activity-of-drugs-against-dormant-mycobacterium-tuberculosis
#6
A Iacobino, G Piccaro, F Giannoni, A Mustazzolu, L Fattorini
OBJECTIVE/BACKGROUND: Heterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043624/new-insights-into-the-mechanism-of-action-of-pyrazinamide-implications-for-susceptibility-testing-and-future-regimens
#7
Richard M Anthony, Alice den Hertog, Mikael Mansjö, Jim Werngren
Pyrazinamide (PZA) is included in the 2016 World Health Organization multidrug-resistant tuberculosis treatment guidelines and is a key component of most ongoing clinical trials investigating novel antibiotic combinations. PZA resistance is associated with worse tuberculosis treatment outcomes. Unfortunately, for such an important drug, phenotypic susceptibility testing is extremely challenging. The exacting bacterial growth conditions required to induce susceptibility to the drug reduce the accuracy of the susceptibility assay, even in experienced laboratories, and widespread testing is not performed...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043604/the-majority-of-patients-with-multidrug-resistant-tuberculosis-in-sub-saharan-africa-present-a-concomitant-resistance-to-pyrazinamide
#8
Géraldine Daneau, Mourad Gumusboga, Pim De Rijk, Arnaud Trebucq, Leen Rigouts, Armand Van Deun, Bouke C de Jong
OBJECTIVE/BACKGROUND: Pyrazinamide (PZA) is an antibacterial used in the first-line regimen against tuberculosis (TB) for its action against dormant bacilli. PZA is also included in the new short regimen to treat multidrug-resistant TB (MDR-TB). However, the prevalence and significance of PZA resistance is not known in Central and West Africa. METHODS: Between 2013 and 2016, we collected samples from MDR-TB patients recruited in an observational study implementing the new short MDR-TB regimen in six countries: Burundi (n=35), Cameroon (n=135), Niger (n=57), Central African Republic (n=35), Democratic Republic of the Congo (n=99), and Rwanda (n=16)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043601/best-approaches-to-drug-resistance-surveillance-at-the-country-level
#9
A M Cabibbe, D M Cirillo
In 2014, the World Health Organization (WHO) recommendation to include the endorsed rapid molecular technologies (Xpert MTB/RIF, line probe assays) into surveillance systems and surveys allowed the testing of more tuberculosis (TB) patients for drug resistance at country level than ever before. The whole genome sequencing (WGS) approach is emerging as a more powerful tool for epidemiological and drug-resistant routine surveillances, promising a rapid and simultaneous screening of all the clinically-relevant mutations for the determination of resistance to the first-, second-line, and new anti-TB drugs...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043597/impact-of-genotypic-and-phenotypic-resistance-to-second-line-anti-tuberculosis-drugs-on-treatment-outcomes-in-multidrug-resistant-tuberculosis-in-china
#10
Yi Hu, Xubin Zheng, Zhu Ning, Qun Li, Zhengdong Zhang, Sven Hoffner
BACKGROUND: Despite the strong association between drug resistance and genetic mutations, the value of molecular diagnosis of drug resistance to guide the treatment of multidrug-resistant tuberculosis (MDR-TB) remains unclear. This is particularly relevant in resource-limited areas, in which it is difficult to implement the drug susceptibility test. Here, we focused on the association of drug susceptibility phenotype and genotype with treatment outcomes in patients with MDR-TB. METHODS: In a prospective cohort study, we enrolled 252 consecutive patients with confirmed MDR-TB between 2010 and 2013, and outcomes were followed-up over the 24-month treatment course in terms of clinical manifestation and sputum conversion...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043555/molecular-identification-of-mycobacterium-tuberculosis-complex-isolates-from-kermanshah-province-iran
#11
Roghieh Moghaddam, Nader Mosavari, Ardeshir Hesampoor Mahalati
Tuberculosis is one of the most important zoonotic diseases in the world. Rapid diagnosis of the disease and identification of species is extremely important for proper treatment of the disease as some species of the complex are resistant to the first-line of tuberculosis drugs. The aim of present study was molecular identification of Mycobacterium tuberculosis (MTB) complex isolates from Kermanshah Province, Iran, which were submitted to the Tuberculosis Reference Laboratory at Razi Vaccine and Serum Research Institute (Tehran, Iran)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043519/increased-expression-of-efflux-pump-genes-in-extensively-drug-resistant-isolates-of-mycobacterium-tuberculosis
#12
Akbar Kanji, Rumina Hasan, Ying Zhang, Wanliang Shi, Kehkashan Imtiaz, Kiran Iqbal, Samreen Shafiq, Zahra Hasan
INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) strains that are multidrug resistant (MDR) and also resistant to a fluoroquinolone and to one injectable aminoglycoside or capreomycin. Whilst resistance in MTB has been associated with single nucleotide polymorphisms (SNPs), efflux pumps are thought to play a role in conferring resistance to MTB but little is known about them. METHODS: We studied XDR MTB (n=10) strains characterized by whole genome sequencing (WGS; http://www...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043510/effects-of-sorbitol-and-glycerol-on-the-structure-dynamics-and-stability-of-mycobacterium-tuberculosis-pyrazinamidase
#13
Mehrnoosh Khajehzadeh, Faramarz Mehrnejad, Mohammad Pazhang, Farahnoosh Doustdar
OBJECTIVE/BACKGROUND: Mycobacterium tuberculosis pyrazinamidase (PZase) is known an enzyme that is involved in degradation of pyrazinamide to ammonia and pyrazinoic acid. Pyrazinamide is an important first-line drug used in the short-course treatment of tuberculosis. Previous investigations have indicated that the pyrazinamide (PZA)-resistant M. tuberculosis strains are caused by point mutations in the PZase enzyme which is the activator of the prodrug PZA. Although the general fold of PZase was determined, the structural and functional properties of the enzyme in solution were not understood very well...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043493/efficacy-and-safety-of-quercetin-and-polyvinylpyrrolidone-in-treatment-of-patients-with-newly-diagnosed-destructive-pulmonary-tuberculosis-in-comparison-with-standard-antimycobacterial-therapy
#14
Dmytro Butov, Svetlana Zaitseva, Tetyana Butova
OBJECTIVE/BACKGROUND: The aim of this work was to study the efficacy and safety of quercetin and polyvinylpyrrolidone (QP) in the treatment of patients with newly diagnosed destructive pulmonary tuberculosis (TB) in comparison with standard antimycobacterial therapy. MATERIALS AND METHODS: The study involved 124 patients aged between 20years and 70years with newly diagnosed destructive pulmonary TB. Patients were allocated to two groups. The first (control) group received standard antimycobacterial and pathogenetic therapy and included 31 (25...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28042401/epidemiology-of-drug-resistant-tuberculosis-in-a-tertiary-care-center-in-oman-2006-2015
#15
Zied Gaifer, Ahmed Babiker, Dawar Rizavi
OBJECTIVES: The aim of this study was to estimate the prevalence and identify the risk factors for the development of drug-resistant Mycobacterium tuberculosis infection in a tertiary care center in Oman. METHODS: We performed a cross-sectional review of culture-confirmed tuberculosis (TB) cases diagnosed at Sultan Qaboos University Hospital between August 2006 and March 2015. We compared drug-resistant TB cases with drug-sensitive cases to identify predictors of drug-resistant TB using univariate and multivariate logistic regression analysis...
January 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28024261/simultaneous-hplc-assay-for-pretomanid-pa-824-moxifloxacin-and-pyrazinamide-in-an-inhaler-formulation-for-drug-resistant-tuberculosis
#16
Mohammad A M Momin, Sim J Thien, Woravimol Krittaphol, Shyamal C Das
A simple and sensitive reversed phase HPLC method has been developed for the simultaneous quantitation of pretomanid (PA-824), moxifloxacin and pyrazinamide in a combination spray-dried powder formulation for inhalation, without any use of an internal standard. Good resolution of the analytes was achieved on a Luna C18 (2), 150×4.6mm, 5μm, 100Å column using gradient elution with a mobile phase containing methanol and triethylamine phosphate buffer (pH 2.5) at a flow rate of 1.0mL/min in a total run time of 25min...
November 25, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28018295/combined-whole-cell-high-throughput-functional-screening-for-identification-of-new-nicotinamidases-pyrazinamidases-in-metagenomic-polygenomic-libraries
#17
Rubén Zapata-Pérez, Antonio G García-Saura, Mohamed Jebbar, Peter N Golyshin, Álvaro Sánchez-Ferrer
Nicotinamidases catalyze the hydrolysis of the amide bond in nicotinamide (NAM) to produce ammonia and nicotinic acid (NA). These enzymes are an essential component of the NAD(+) salvage pathway and are implicated in the viability of several pathogenic organisms. Its absence in humans makes them a promising drug target. In addition, although they are key analytical biocatalysts for screening modulators in relevant biomedical enzymes, such as sirtuins and poly-ADP-ribosyltransferases, no commercial sources are available...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28012685/pnca-mutations-are-associated-with-slower-sputum-conversion-during-standard-treatment-of-multidrug-resistant-tuberculosis
#18
Xubin Zheng, Zhu Ning, Francis Drobniewski, Jingyong Yang, Qun Li, Zhengdong Zhang, Yi Hu
Despite the strong association between drug resistance and genetic mutations, the value of molecular diagnosis of drug resistance to guide the treatment of multidrug-resistant tuberculosis (MDR-TB) remains unclear. This is particularly relevant in resource-limited areas where it is difficult to perform drug susceptibility testing (DST). Here we investigated the association between drug susceptibility phenotypes and genotypes and treatment outcomes in patients with MDR-TB. This study enrolled 74 consecutive patients with confirmed MDR-TB between 2010 and 2011, and outcomes were followed-up over the 24-month treatment course...
November 24, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28011331/multi-drug-resistant-female-genital-tuberculosis-a-preliminary-report
#19
J B Sharma, Alka Kriplani, Eshani Sharma, Sangeeta Sharma, Sona Dharmendra, Sunesh Kumar, P Vanamail, S K Sharma
OBJECTIVE: Evaluation of 6 patients presenting with tubo-ovarian mass or infertility with multi drug resistant (MDR) female genital tuberculosis (FGTB). STUDY DESIGN: It was an observational study in a tertiary referral centre, India on subjects with MDR FGTB on clinical examination and investigations. All patients were given category IV drugs using kanamycin (intramuscular), levofloxacin, pyrazinamide, cycloserine, ethionamide and ethambutol (or para aminosalicylic acid [PAS] for ethambutol resistant cases) for 6 months intensive phase followed by oral levofloxacin, cycloserine, ethionamide and ethambutol (or PAS for ethambutol resistant cases) for 18 months continuation phase...
December 12, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28011126/drug-drug-cocrystals-of-antituberculous-4-aminosalicylic-acid-screening-crystal-structures-thermochemical-and-solubility-studies
#20
Ksenia V Drozd, Alex N Manin, Andrei V Churakov, German L Perlovich
Experimental multistage cocrystal screening of the antituberculous drug 4-aminosalicylic acid (PASA) has been conducted with a number of coformers (pyrazinamide (PYR), nicotinamide (NAM), isonicotinamide (iNAM), isoniazid (INH), caffeine (CAF) and theophylline (TPH)). The crystal structures of 4-aminosalicylic acid cocrystals with isonicotinamide ([PASA+iNAM] (2:1)) and methanol solvate with caffeine ([PASA+CAF+MeOH] (1:1:1)) have been determined by single X-ray diffraction experiments. For the first time for PASA cocrystals it has been found that the structural unit of the [PASA+iNAM] cocrystal (2:1) is formed by 2 types of heterosynthons: acid-pyridine and acid-amide...
December 20, 2016: European Journal of Pharmaceutical Sciences
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