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https://www.readbyqxmd.com/read/28630430/a-multinational-analysis-of-mutations-and-heterogeneity-in-pzase-rpsa-and-pand-associated-with-pyrazinamide-resistance-in-m-xdr-mycobacterium-tuberculosis
#1
S M Ramirez-Busby, T C Rodwell, L Fink, D Catanzaro, R L Jackson, M Pettigrove, A Catanzaro, F Valafar
Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA molecular diagnostics in M/XDR TB cases. A set of 296, mostly XDR, clinical M. tuberculosis isolates from four countries were subjected to DST for eight drugs, confirmatory Wayne's assay, and whole-genome sequencing...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630203/bactericidal-and-sterilizing-activity-of-a-novel-regimen-with-bedaquiline-pretomanid-moxifloxacin-and-pyrazinamide-in-a-murine-model-of-tuberculosis
#2
Si-Yang Li, Rokeya Tasneen, Sandeep Tyagi, Heena Soni, Paul J Converse, Khisimuzi Mdluli, Eric L Nuermberger
New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) + pretomanid (PMD) + pyrazinamide (PZA) and of PMD + moxifloxacin (MXF) + PZA shorten the treatment duration necessary to prevent relapse by 2-3 and 1-2 months, respectively, compared with the current first-line regimen in a murine TB model. These 3-drug combinations are now being studied in clinical trials...
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
#3
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/28610794/molecular-mechanisms-of-action-resistance-detection-to-the-first-line-anti-tuberculosis-drugs-rifampicin-and-pyrazinamide-in-the-post-whole-genome-sequencing-era
#4
REVIEW
Ameeruddin Nusrath Unissa, Luke Elizabeth Hanna
Recent studies in addition to studies based on whole genome sequencing (WGS) of clinical isolates of Mycobacterium tuberculosis (MTB) from diverse geographical regions have provided useful insights into the mechanisms of drug resistance. Of importance, are some of the findings pertaining to mechanisms of resistance to two of the first-line anti-tuberculosis (TB) drugs, namely, rifampicin (RIF) and pyrazinamide (PZA). For example, the implication of mutations in rpoA and rpoC genes that act as compensatory mutations for those in the rpoB gene with respect to RIF resistance is noteworthy...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610782/assessment-of-treatment-response-by-colony-forming-units-time-to-culture-positivity-and-the-molecular-bacterial-load-assay-compared-in-a-mouse-tuberculosis-model
#5
Gerjo J de Knegt, Laura Dickinson, Henry Pertinez, Dimitrios Evangelopoulos, Timothy D McHugh, Irma A J M Bakker-Woudenberg, Gerry R Davies, Jurriaan E M de Steenwinkel
The aim of the study is to compare counting of colony forming units (CFU), the time to positivity (TTP) assay and the molecular bacterial load (MBL) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. CFU counting, TTP and the MBL assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. Mice were treated for 24 weeks with 4 treatment arms: isoniazid (H) - rifampicin (R) - pyrazinamide (Z), HRZ-Streptomycin (S), HRZ - ethambutol (E) or ZES...
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/28604689/pyrazinamide-and-derivatives-block-ethylene-biosynthesis-by-inhibiting-acc-oxidase
#7
Xiangzhong Sun, Yaxin Li, Wenrong He, Chenggong Ji, Peixue Xia, Yichuan Wang, Shuo Du, Hongjiang Li, Natasha Raikhel, Junyu Xiao, Hongwei Guo
Ethylene is an important phytohormone that promotes the ripening of fruits and senescence of flowers thereby reducing their shelf lives. Specific ethylene biosynthesis inhibitors would help to decrease postharvest loss. Here, we identify pyrazinamide (PZA), a clinical drug used to treat tuberculosis, as an inhibitor of ethylene biosynthesis in Arabidopsis thaliana, using a chemical genetics approach. PZA is converted to pyrazinecarboxylic acid (POA) in plant cells, suppressing the activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), the enzyme catalysing the final step of ethylene formation...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587904/evaluation-of-a-novel-line-probe-assay-to-detect-resistance-to-pyrazinamide-a-key-drug-used-for-tuberculosis-treatment
#8
Michèle Driesen, Yuji Kondo, Bouke C de Jong, Gabriela Torrea, Sylvie Asnong, Christel Desmaretz, Kamal S M Mostofa, Sabira Tahseen, Michael G Whitfield, Daniela M Cirillo, Paolo Miotto, Andrea M Cabibbe, Leen Rigouts
OBJECTIVES: The development of rapid molecular diagnostic assays for pyrazinamide (PZA) resistance is considered technically challenging as mutations are highly diverse, scattered along the full length of the pncA gene, and not all are associated with PZA resistance. In this study, we evaluated the performance of the novel Genoscholar PZA-TB II line-probe assay (NIPRO Corporation, Japan; 'PZA-LPA2'). METHODS: To evaluate the applicability of the PZA-LPA2 in clinical settings, we compared the performance of the PZA-LPA2 to a composite reference standard pncA Sanger and Illumina sequencing plus phenotypic susceptibility testing on a panel of 87 Mycobacterium tuberculosis isolates from WHO drug resistance surveys, harbouring mutations previously classified as associated or not associated with resistance according to data from peer-reviewed literature...
June 3, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28586626/delayed-and-unreported-drug-susceptibility-testing-results-in-the-us-national-tuberculosis-surveillance-system-1993-2014
#9
Jefferson Michael Jones, Lori R Armstrong
OBJECTIVES: Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System. METHODS: We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results...
January 1, 2017: Public Health Reports
https://www.readbyqxmd.com/read/28584158/identification-of-novel-efflux-proteins-rv0191-rv3756c-rv3008-and-rv1667c-involved-in-pyrazinamide-resistance-in-mycobacterium-tuberculosis
#10
Yumeng Zhang, Jia Zhang, Peng Cui, Wenhong Zhang, Ying Zhang
Pyrazinamide (PZA) is a critical drug used for the treatment of tuberculosis (TB). PZA is a prodrug that requires conversion to the active component pyrazinoic acid (POA) by pyrazinamidase (PZase) encoded by the pncA gene. Although resistance to PZA is mostly caused by pncA mutations and less commonly by rpsA, panD, and clpC1, clinical strains without these mutations are known to exist. While efflux of POA was demonstrated in Mycobacterium tuberculosis previously, the efflux proteins involved have not been identified...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28570955/-1-h-nmr-spectral-identification-of-medication-in-cerebrospinal-fluid-of-pediatric-meningitis
#11
Shayne Mason, Carolus J Reinecke, Regan Solomons, Ron A Wevers, Udo F H Engelke
Exploratory metabolomics studies of cerebrospinal fluid (CSF), using proton nuclear magnetic resonance ((1)H NMR) spectroscopy, hold major potential application in neurodiagnostics. Such studies, however, rely upon established databases of known metabolites. Here we address the 'unknowns' in the (1)H NMR spectra of CSF from treated pediatric meningitis cases. Through knowledge of the clinical information given by the pediatrician and analytical application of (1)H NMR spectroscopy on pure reference compounds of the medication used, we identified four of the previously unknown compounds in the (1)H NMR CSF spectra - the drugs pyrazinamide, isoniazid, acyclovir, and sulfamethoxazole...
May 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28559517/characterization-of-pyrazinamide-resistance-in-consecutive-multidrug-resistant-mycobacterium-tuberculosis-isolates-in-sweden-between-2003-and-2015
#12
Mikael Mansjo, Jim Werngren, Sven Hoffner
BACKGROUND: The first line anti-tuberculosis drug pyrazinamide (PZA) is important when treating PZA susceptible multidrug-resistant tuberculosis (MDR-TB). Several drug resistance surveys have however reported PZA resistance among a significant proportion of multidrug-resistant (MDR) cases and this undoubtedly highlights the need for accurate and reliable detection of PZA resistance. Unfortunately, the testing of PZA susceptibility is associated with technical difficulties and even though the introduction of pncA sequencing has helped to address this issue, misclassification may still occur...
April 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28539499/reply-to-anthony-et-al-protecting-pyrazinamide-a-priority-for-improving-outcomes-in-multidrug-resistant-tuberculosis-treatment
#13
M O Fofana, D W Dowdy
No abstract text is available yet for this article.
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28538778/estimated-rates-of-recurrence-cure-and-treatment-abandonment-in-patients-with-pulmonary-tuberculosis-treated-with-a-four-drug-fixed-dose-combination-regimen-at-a-tertiary-health-care-facility-in-the-city-of-rio-de-janeiro-brazil
#14
Vangie Dias da Silva, Fernanda Carvalho de Queiroz Mello, Sonia Catarina de Abreu Figueiredo
Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil...
March 2017: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
https://www.readbyqxmd.com/read/28515572/a-family-of-fe-n-c-oxygen-reduction-electrocatalysts-for-microbial-fuel-cell-mfc-application-relationships-between-surface-chemistry-and-performances
#15
Carlo Santoro, Alexey Serov, Rohan Gokhale, Santiago Rojas-Carbonell, Lydia Stariha, Jonathan Gordon, Kateryna Artyushkova, Plamen Atanassov
Different iron-based cathode catalysts have been studied for oxygen reduction reaction (ORR) in neutral media and then applied into microbial fuel cells (MFC). The catalysts have been synthesized using sacrificial support method (SSM) using eight different organic precursors named Niclosamide, Ricobendazole, Guanosine, Succinylsulfathiazole, Sulfacetamide, Quinine, Sulfadiazine and Pyrazinamide. Linear Sweep Voltammetry (LSV) curves were obtained for the catalysts using a O2 saturated in 0.1 M potassium phosphate buffer and 0...
May 15, 2017: Applied Catalysis. B, Environmental
https://www.readbyqxmd.com/read/28506804/chloroquine-enhances-the-antimycobacterial-activity-of-isoniazid-and-pyrazinamide-by-reversing-inflammation-induced-macrophage-efflux
#16
U Matt, P Selchow, M Dal Molin, S Strommer, O Sharif, K Schilcher, F Andreoni, A Stenzinger, A S Zinkernagel, M Zeitlinger, P Sander, J Nemeth
Mycobacterium tuberculosis (MTB) is notorious for persisting within host macrophages. Efflux pumps decrease intracellular drug levels, thus fostering persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of MTB infection. In the current in vitro study, interferon-gamma (IFNγ) increased the expression of BCRP-1 in macrophages derived from the human monocytic leukaemia cell line THP-1...
May 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28503547/theoretically-guided-analytical-method-development-and-validation-for-the-estimation-of-rifampicin-in-a-mixture-of-isoniazid-and-pyrazinamide-by-uv-spectrophotometer
#17
Mohammad F Khan, Shamima A Rita, Md Shahidulla Kayser, Md Shariful Islam, Sharmeen Asad, Ridwan Bin Rashid, Md Abdul Bari, Muhammed M Rahman, D A Anwar Al Aman, Nurul I Setu, Rebecca Banoo, Mohammad A Rashid
A simple, rapid, economic, accurate, and precise method for the estimation of rifampicin in a mixture of isoniazid and pyrazinamide by UV spectrophotometeric technique (guided by the theoretical investigation of physicochemical properties) was developed and validated. Theoretical investigations revealed that isoniazid and pyrazinamide both were freely soluble in water and slightly soluble in ethyl acetate whereas rifampicin was practically insoluble in water but freely soluble in ethyl acetate. This indicates that ethyl acetate is an effective solvent for the extraction of rifampicin from a water mixture of isoniazid and pyrazinamide...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28501621/discovery-of-a-novel-prolyl-trna-synthetase-inhibitor-and-elucidation-of-its-binding-mode-to-the-atp-site-in-complex-with-l-proline
#18
Ryutaro Adachi, Kengo Okada, Robert Skene, Kazumasa Ogawa, Masanori Miwa, Kazuhiro Tsuchinaga, Shoichi Ohkubo, Tsutomu Henta, Tomohiro Kawamoto
Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family of enzymes and catalyzes the synthesis of prolyl-tRNA(Pro) using ATP, l-proline, and tRNA(Pro) as substrates. An ATP-dependent PRS inhibitor, halofuginone, was shown to suppress autoimmune responses, suggesting that the inhibition of PRS is a potential therapeutic approach for inflammatory diseases. Although a few PRS inhibitors have been derivatized from natural sources or substrate mimetics, small-molecule human PRS inhibitors have not been reported...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28489185/risk-factors-associated-with-multidrug-resistant-tuberculosis-in-esp%C3%A3-rito-santo-brazil
#19
Geisa Fregona, Lorrayne Belique Cosme, Cláudia Maria Marques Moreira, José Luis Bussular, Valdério do Valle Dettoni, Margareth Pretti Dalcolmo, Eliana Zandonade, Ethel Leonor Noia Maciel
OBJECTIVE: To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. METHODS: This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis - from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose...
April 27, 2017: Revista de Saúde Pública
https://www.readbyqxmd.com/read/28480653/the-rate-of-drug-resistant-tuberculosis-in-korean-children-and-adolescents-since-2007
#20
Hyun Jung Kim, Hyung Ho Yoon, Byung Wook Eun, Youngmin Ahn, Sungweon Ryoo, Hee Jin Kim
The incidence of drug-resistant tuberculosis (DR-TB) in pediatric populations is a critical indicator of national TB management and treatment strategies. Limited data exist regarding the rate of pediatric DR-TB. In this study, we aimed to analyze the status of DR-TB in Korean children from 2007 to 2013. We analyzed specimens submitted to the Korean Institute of Tuberculosis using Mycobacterium tuberculosis culture and drug susceptibility tests (DSTs) from January 2007 through December 2013. Specimens from patients ≤ 19 years of age were included...
June 2017: Journal of Korean Medical Science
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