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Daniel Rueda, Roberto Furukawa, Patricia Fuentes, Germán Comina, Nicolás G Rey De Castro, David Requena, Robert H Gilman, Patricia Sheen, Mirko Zimic
Introduction: Tuberculosis (TB) is a significant cause of morbidity and mortality worldwide. The patient compliance with the long treatment regimens is essential for successful eradication. Pyrazinamide (PZA) shortens these regimens from 9 to 6 months, and therefore, improves treatment completion rates. Although PZA is a first-line medication for the treatment of TB, no simple or reliable assay to determine PZA resistance is yet available. In the presence of PZA, only susceptible Mycobacterium tuberculosis strains release pyrazinoic acid (POA)...
July 2018: International Journal of Mycobacteriology
Mohadese Khajehzadeh, Saeedeh Khaleghnejad, Faramarz Mehrnejad, Mohammad Pazhang, Farahnoosh Doustdar
Background: In this study, we have experimentally investigated the effects of different osmolytes including sucrose, sorbitol, urea, and guanidinium chloride (GdmCl) on the stability and structure of the Mycobacterium tuberculosis pyrazinamidase (PZase). PZase converts pyrazinamide to its active form. Methods: In addition, in order to gain molecular insight into the interactions between osmolytes and PZase, we have conducted 1000-ns molecular dynamics simulations...
July 2018: International Journal of Mycobacteriology
Karen Santos, Pradeep B Lukka, Anne Grzegorzewicz, Mary Jackson, Ashit Trivedi, Fernando Pavan, Marlus Chorilli, Miriam Braunstein, Anthony Hickey, Bernd Meibohm, Mercedes Gonzalez-Juarrero
There is an urgent need to treat tuberculosis (TB) quickly, effectively and without side effects. Mycobacterium tuberculosis (Mtb), the causative organism of TB, can survive for long periods of time within macrophages and dendritic cells and these intracellular bacilli are difficult to eliminate with current drug regimens. It is well established that Mtb responds differentially to drug treatment depending on its extracellular and intracellular location and replicative state. In this study, we isolated and cultured lung derived dendritic cells to be used as a screening system for drug efficacy against intracellular mycobacteria...
2018: Frontiers in Microbiology
N Ismail, S V Omar, N A Ismail, R P H Peters
Bedaquiline, clofazimine and linezolid are pertinent drugs for drug-resistant tuberculosis. Drug-resistant mutants provide insight into important resistance acquisition mechanisms. Methods for in vitro Mycobacterium tuberculosis mutant generation are poorly described. Induction (serial passaging) and spontaneous (adapted Luria-Delbrück assay) approaches using M. tuberculosis ATCC reference strains (one fully-susceptible, four unique mono-resistant) were performed. Mutant MIC values were confirmed (MGIT960) and resultant RAVs compared between approaches and to a catalog of previously published RAVs...
August 28, 2018: Journal of Microbiological Methods
Marylette B Roa, Francis A Tablizo, El King D Morado, Lovette F Cunanan, Iris Diana C Uy, Kamela Charmaine S Ng, Karen G Manalastas-Cantos, Joeriggo M Reyes, Sharie Keanne C Ganchua, Concepcion F Ang, Midori Kato-Maeda, Adithya Cattamanchi, Ulas Karaoz, Raul V Destura, Arturo O Lluisma
OBJECTIVES: Thousands of cases of multi-drug resistant Mycobacteria tuberculosis (MTB) have been observed in the Philippines but studies on the genotypes that underlie the observed drug resistance profiles have been lacking. This study aimed to analyse whole genomes of clinical isolates of MTB representing varying resistance profiles to identify single nucleotide polymorphisms (SNPs) in resistance-associated genes. METHODS: The genomes of ten MTB isolates cultured from banked sputum sources were sequenced...
August 18, 2018: Journal of Global Antimicrobial Resistance
Ruoqiong Cao, Garrett Teskey, Hicret Islamoglu, Rachel Abrahem, Shalok Munjal, Karo Gyurjian, Li Zhong, Vishwanath Venketaraman
Mycobacterium tuberculosis ( M. tb ) is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, with an ever-increasing resistance to antibiotics. We tested the synergistic effects of N-acetyl cysteine (NAC, the precursor molecule for the synthesis of glutathione) and individual first-line antibiotics typically given for the treatment of TB such as Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA) to improve the ability of macrophages to control intracellular M...
August 20, 2018: Antimicrobial Agents and Chemotherapy
Omamah Alfarisi, Vidya Mave, Sanjay Gaikwad, Tushar Sahasrabudhe, Geetha Ramachandran, Hemanth Kumar, Nikhil Gupte, Vandana Kulkarni, Sona Deshmukh, Sachin Atre, Swapnil Raskar, Rahul Lokhande, Madhusudan Barthwal, Arjun Kakrani, Amita Gupta, Jonathan E Golub, Kelly E Dooley
Background: Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics and pharmacodynamics of anti-TB drugs remains poorly-characterized. Methods: Newly-diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (pre-dose, 0.5, 2, 6 hours post-dose) during intensive and continuation phases of treatment...
August 20, 2018: Antimicrobial Agents and Chemotherapy
Andréanne Lupien, Anthony Vocat, Caroline Shi-Yan Foo, Emilyne Blattes, Jean-Yves Gillon, Vadim Makarov, Stewart T Cole
The efficacy of the standardized four-drug regimen (comprising isoniazid, rifampicin, pyrazinamide and ethambutol) for the treatment of tuberculosis (TB) is menaced by the emergence of multidrug (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis Intensive efforts have been made to develop new antibiotics or to repurpose old drugs and several of these are currently being evaluated in clinical trials for their anti-tubercular activity. Among the new candidate drugs is macozinone (MCZ), the piperazine-containing benzothiazinone, PBTZ169, which is currently being evaluated in phase I/II clinical trials...
August 20, 2018: Antimicrobial Agents and Chemotherapy
Katarina Niward, Lina Davies Forsman, Judith Bruchfeld, Erja Chryssanthou, Oskar Carlström, Teba Alomari, Björn Carlsson, Anton Pohanka, Mikael Mansjö, Michaela Jonsson Nordvall, Anders G Johansson, Erik Eliasson, Jim Werngren, Jakob Paues, Ulrika S H Simonsson, Thomas Schön
Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline...
August 14, 2018: Journal of Antimicrobial Chemotherapy
Luisa Kramer, Vanessa Geib, John Evison, Ekkehardt Altpeter, Jasmin Basedow, Jan Brügger
BACKGROUND: Tuberculosis is the leading infectious cause of death worldwide. Among native Swiss people, tuberculosis is more common in older people than in younger people. Approximately 25-30% of reported cases of tuberculosis are purely extrapulmonary; skeletal tuberculosis is reported in 3-5% of cases. The purpose of this case report is to draw attention to the diagnostic challenge of tuberculous sacroiliitis with secondary psoas abscess, as this clinical picture is very rare. CASE PRESENTATION: A magnetic resonance imaging scan of an 85-year-old (Swiss-German) Caucasian woman with chronic left-sided hip pain and limitation of hip joint movement showed a progressive destruction of her sacroiliac joint and a large collection in her left iliopsoas muscle...
August 18, 2018: Journal of Medical Case Reports
Dmytro Butov, Yurii Feshchenko, Mykhailo Kuzhko, Mykola Gumeniuk, Tetiana Butova
The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase for patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). MATERIALS AND METHODS: The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 years and 68 years. All patient with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in this study. The patients were allocated to two groups. The first (control) group of 46 patients received standard chemotherapy orally...
August 15, 2018: Advances in Respiratory Medicine
Jan Zitko, Ondřej Jand'ourek, Pavla Paterová, Lucie Navrátilová, Jiří Kuneš, Jarmila Vinšová, Martin Doležal
Hybrid compounds based on a combination of the first-line antitubercular pyrazinamide (PZA) and a formerly identified antimycobacterial scaffold of 4-arylthiazol-2-amine were designed. Eighteen compounds were prepared, characterized and tested for in vitro growth inhibition activity against M. tuberculosis H37Rv, M. kansasii , M. avium and M. smegmatis by Microplate Alamar Blue Assay at neutral pH. Active compounds were tested for in vitro cytotoxicity in the human hepatocellular carcinoma cell line (HepG2)...
April 1, 2018: MedChemComm
Muzafar Ahmad Rather, Ali Mohd Lone, Bisma Teli, Zubair Shanib Bhat, Paramjeet Singh, Mubashir Maqbool, Bashir Ahmad Shairgojray, Mohd Jamal Dar, Shajrul Amin, Syed Khalid Yousuf, Bilal A Bhat, Zahoor Ahmad
The present study utilised whole cell based phenotypic screening of thousands of diverse small molecules against Mycobacterium tuberculosis H37Rv ( M. tuberculosis ) and identified the cyclohexane-1,3-dione-based structures 5 and 6 as hits. The selected hit molecules were used for further synthesis and a library of 37 compounds under four families was synthesized for lead generation. Evaluation of the library against M. tuberculosis lead to the identification of three lead antituberculosis agents ( 37 , 39 and 41 )...
November 1, 2017: MedChemComm
Kazuhiko Hashimoto, Shunji Nishimura, Naohiro Oka, Ryosuke Kakinoki, Masao Akagi
Despite the increasing incidence of tuberculosis, even in developed countries like Japan, tuberculoma is a relatively uncommon disease. Furthermore, given the rarity of tuberculoma, a definitive diagnosis is often delayed. We herein present the case of a 79-year-old man who presented with an erythematous and warm mass in the left forearm. Radiography revealed calcification of the wrist's volar side, and magnetic resonance imaging revealed a mosaic pattern at the lesion. Soft tissue sarcoma of the wrist was suspected, and an incisional biopsy was performed, which revealed numerous yellow rice bodies...
August 2018: Molecular and Clinical Oncology
Dhanashree Lokesh, Raman Parkesh, Rajagopal Kammara
Multiple mutations in the β subunit of the RNA polymerase (rpoβ) of Mycobacterium tuberculosis (Mtb) are the primary cause of resistance to rifamycin (RIF). In the present study, bifidobacterial rpoβ sequences were analyzed to characterize the mutations that contribute to the development of intrinsic resistance to RIF, isoniazid, streptomycin and pyrazinamide. Sequence variations, which mapped to cassettes 1 and 2 of the rpoβ pocket, are also found in multidrug-resistant Mtb (MDR Mtb). Growth curves in the presence of osmolytes and different concentrations of RIF showed that the bacteria adapted rapidly by shortening the growth curve lag time...
August 9, 2018: Scientific Reports
Mohammad H Al-Shaer, Hazem Elewa, Yosra Alkabab, Lama H Nazer, Scott K Heysell
BACKGROUND: Diabetes is associated with increased risk of tuberculosis (TB) treatment failure, death, and relapse compared to patients without diabetes. Current TB regimens are available as fixed dose combination (FDC) and separate tablets (ST), in which using the former is purported to make it easier to adhere and complete treatment. So far there are no studies assessing the performance of FDC compared to ST in diabetic patients with pulmonary TB. METHODOLOGY: A retrospective cohort study was conducted, and included eight hospitals in Qatar in which patients diagnosed with pulmonary TB received rifampin, isoniazid, pyrazinamide, and ethambutol (as FDC or ST) given as directly observed therapy...
August 8, 2018: BMC Infectious Diseases
Amal Atta, Salwa Fahmy, Ola Rizk, Dharmarajan Sriram, Mona A Mahran, Ibrahim M Labouta
New pyridine derivatives were designed and synthesized as Isonicotinic acid hydrazide (INH) analogues. The synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis strain H37 Rv . Ten compounds (3c, 3e-g, 5a-c, 6h, 10 and 11b) showed promising antitubercular activity with MIC range 7.30 µM-19.39 µM. Compounds 3e, 3g, 5b and 11b were the most potent analogues, with MIC 7.30-8.74 µM. They were equipotent to the standard drug Ethambutol (MIC 7.64 µM) and more active than the standard drug Pyrazinamide (MIC 50...
October 2018: Bioorganic Chemistry
Sabine L van Elsland, Remco P H Peters, Maarten O Kok, Ronald van Toorn, Priscilla Springer, Mark F Cotton, Cornelis J Grobbelaar, Rob Aarnoutse, A Marceline van Furth
OBJECTIVES: To evaluate a paediatric treatment-support intervention for home-based treatment of HIV infection or tuberculous meningitis (TBM). METHODS: A randomised-controlled study comparing local standard care (controls) with standard care plus intervention (combining adherence education, reinforcement and monitoring) in children aged 0-14 years. We recorded adherence measures (self-report, pill-count, drug-assays for isoniazid and rifampicin in urine and pyrazinamide in saliva), difficulties administering medication and PedsQL™questionnaires for health-related quality-of-life (HRQoL) and family impact...
August 3, 2018: Tropical Medicine & International Health: TM & IH
Asmita Gupte, Anupama Matcha, Michael Lauzardo
BCG has been used as intravesical immunotherapy for the treatment of bladder carcinoma. However, this treatment is not harmless and may lead to complications, with a reported incidence of systemic BCG infection ranging from 3% to 7%. We report a case of culture-proven Mycobacterium bovis (BCG) vertebral osteomyelitis in a 72-year-old patient with bladder carcinoma who was treated with intravesical mitomycin C but did not receive BCG. Cultures from biopsy recovered isolate resembling Mycobacterium tuberculosis biochemically, but resistant to pyrazinamide (PZA)...
July 30, 2018: BMJ Case Reports
Lisa Mangum, Dustin Kilpatrick, Barbara Stryjewska, Rahul Sampath
Both leprosy and tuberculosis (TB) are known to have similar geographic endemicity. In the setting of coinfection, interferon-gamma release assays (IGRAs) to detect latent TB can be falsely positive. We report a case of leprosy with a positive IGRA and asymptomatic active pulmonary TB. Minocycline and dapsone therapy was initiated during the workup for TB and changed to rifampin (Rif), isoniazid, pyrazinamide, and ethambutol, with the addition of dapsone once coinfection was confirmed. Our review of the literature revealed a preponderance of coinfection reported with borderline and lepromatous disease...
July 2018: Open Forum Infectious Diseases
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