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Chen Zhu, Yu Liu, Lihua Hu, Min Yang, Zheng-Guo He
Isoniazid (INH) and ethambutol (EMB) are two major first-line drugs for managing tuberculosis (TB), caused by the microbe Mycobacterium tuberculosis Although co-use of these two drugs is common in clinical practice, the mechanism for the potential synergistic interplay between them remains unclear. Here, we present first evidence that INH and EMB act synergistically through a transcriptional repressor of the inhA gene, the target gene of INH encoding an enoyl-acyl carrier protein reductase of the fatty acid synthase type II system required for bacterial cell wall integrity...
September 5, 2018: Journal of Biological Chemistry
Mikhail Krasavin, Alexei Lukin, Tatiana Vedekhina, Olga Manicheva, Marine Dogonadze, Tatiana Vinogradova, Natalia Zabolotnykh, Elizaveta Rogacheva, Liudmila Kraeva, Piotr Yablonsky
Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. tuberculosis strains in vitro. One of the compounds displayed promising potent activity (MIC 0.8 μg/mL) against one of such strains otherwise resistant to such first- and second-line TB therapies as streptomycin, isoniazid, rifampicin, ethambutol, kanamycin, ethionamide, capreomycin and amikacin...
August 29, 2018: European Journal of Medicinal Chemistry
Edward Helal-Neto, Suyene Rocha Pinto, Filipe Leal Portilho, Marcellus Dias da Costa, Jonathas Xavier Pereira, Fiammetta Nigro, Eduardo Ricci-Junior, Andre Luis Peixoto Candéa, Maria das Graças Muller de Oliveira Henriques, Ralph Santos-Oliveira
In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells...
September 3, 2018: Drug Delivery and Translational Research
Lidya Chaidir, Carolien Ruesen, Bas E Dutilh, Ahmad R Ganiem, Anggriani Andryani, Lika Apriani, Martijn A Huynen, Rovina Ruslami, Philip C Hill, Reinout van Crevel, Bachti Alisjahbana
BACKGROUND: Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected. METHODS: We applied WGS in strains from 322 adult HIV-negative TB patients. Phenotypic DST was done for a portion of patients. RESULTS: Fifty-one isolates (15...
August 29, 2018: Journal of Global Antimicrobial Resistance
Tapinder Kaur Grewal, Shahnawaz Majeed, Sadhna Sharma
Background & objectives: Mycobacterium avium causes atypical infection in both immunocompetent and immunocompromised individuals. Conventional chemotherapy for M. avium infection is not efficient due to lengthy course of treatment and drug-associated toxic side effects. The present study was aimed at reducing dosing frequency of antimicrobial regimen consisting of azithromycin (AZM), rifabutin (RBT) and ethambutol (EMB) by encapsulation of drugs in nanoparticles (NPs) in experimental M...
June 2018: Indian Journal of Medical Research
Rie R Yotsu, Marty Richardson, Norihisa Ishii
BACKGROUND: Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery. OBJECTIVES: To summarize the evidence of drug treatments for treating Buruli ulcer...
August 23, 2018: Cochrane Database of Systematic Reviews
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
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
U Venkatesh, D K Srivastava, A K Srivastava, H C Tiwari
Introduction: Multidrug-resistant tuberculosis (MDR-TB) poses a major threat to control of TB worldwide. Adequate information on socioepidemiological factors and their interaction is required for its control. The aim was to study the social and epidemiological profile of MDR-TB patient in Gorakhpur division. Methodology: A cross-sectional study of 157 MDR-TB patients from Gorakhpur division admitted at DR-TB Center of a tertiary care center were interviewed during initiation of MDR-TB treatment using structured questionnaire and collected data were described using descriptive statistics...
May 2018: Journal of Family Medicine and Primary Care
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
Zubair Shanib Bhat, Hafiz Ul Lah, Muzafar Ahmad Rather, Mubashir Maqbool, Tabassum Ara, Zahoor Ahmad, Syed Khalid Yousuf
Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2 H -pyran-2-ones (CHPs) ( 2a-2y ) was synthesized and evaluated against a standard virulent laboratory strain of Mycobacterium tuberculosis H37Rv. Out of 25 compounds, 11 , 5 , 7 and 2 ( 2a and 2u ) showed least, moderate, good and appreciable activities, respectively, based on minimum inhibitory concentrations (MICs). Both 2a and 2u exhibited an MIC value of 4 μg ml-1 , which was close to those of standard antituberculosis drugs ethambutol, streptomycin and levofloxacin...
January 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
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
D S Chauhan, R Sharma, D Parashar, R Das, P Sharma, A V Singh, P K Singh, K Katoch, V M Katoch
Background: Early diagnosis of drug resistance (DR) to ethambutol (EMB) in tuberculosis (TB) remains a challenge. Simple and reliable method (s) are needed for rapid detection of DR Mycobacterium tuberculosis (MTB) in clinical specimens. Objectives: The aim of this study was to design fluorescence resonance energy transfer hybridisation probe-based real-time polymerase chain reaction (PCR) method for the early detection of EMB-resistant MTB direct from clinical sputa...
April 2018: Indian Journal of Medical Microbiology
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
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
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