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Aryadne L de Almeida, Katiany R Caleffi-Ferracioli, Regiane B de L Scodro, Vanessa P Baldin, Débora C Montaholi, Luiza F Spricigo, Sandra S Nakamura-Vasconcelos, Laíse A Hegeto, Eloísa G Sampiron, Giovana F Costacurta, Diego A Dos S Yamazaki, Gisele de F Gauze, Vera Ld Siqueira, Rosilene F Cardoso
AIM:  To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. MATERIALS & METHODS:  Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter...
February 13, 2019: Future Microbiology
Manabu Nagata, Goh Ohji, Kentaro Iwata
BACKGROUND: There are many side effects of antituberculous drugs, however, renal failure is relatively rare. Therefore, this side effect is thought to be unrecognized by most physicians. We experienced one case of acute renal failure caused by antituberculous therapy (rifampicin). CASE REPORT: A 64-year-old Japanese male developed tuberculous pleuritis. Six weeks after starting isoniazid (INH), rifampicin (RFP), and ethambutol (EB), his renal function worsened. We temporarily stopped antituberculous therapy, but the patient's renal failure did not improve, and he was admitted to our hospital for renal biopsy...
February 10, 2019: International Journal of Clinical Pharmacology and Therapeutics
Saumu Pazia Juma, Athanasia Maro, Suporn Pholwat, Stellah G Mpagama, Jean Gratz, Alphonse Liyoyo, Eric R Houpt, Gibson S Kibiki, Blandina T Mmbaga, Scott K Heysell
BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious disease and the roll-out of rapid molecular diagnostics for rifampin resistance has resulted in a steady rise in the number of patients with multidrug-resistant (MDR)-TB referred for treatment. Pyrazinamide is used in susceptible TB treatment for 6 months when used in combination with rifampin, isoniazid and ethambutol and is an important companion drug in novel MDR-TB trials. This study was undertaken to determine the prevalence of pyrazinamide resistance by either phenotypic or pncA testing among patients admitted to a referral hospital in Tanzania for drug-susceptible and MDR-TB treatment...
February 7, 2019: BMC Infectious Diseases
Himani Tandon, Arun Sharma, Sankaran Sandhya, Narayanaswamy Srinivasan, Ramandeep Singh
Toxin-antitoxin (TA) systems are ubiquitously existing addiction modules with essential roles in bacterial persistence and virulence. The genome of Mycobacterium tuberculosis encodes approximately 79 TA systems. Through computational and experimental investigations, we report for the first time that Rv0366c-Rv0367c is a non-canonical PezAT-like toxin-antitoxin system in M. tuberculosis. Homology searches with known PezT homologues revealed that residues implicated in nucleotide, antitoxin-binding and catalysis are conserved in Rv0366c...
February 4, 2019: Scientific Reports
Sebastian M Gygli, Peter M Keller, Marie Ballif, Nicolas Blöchliger, Rico Hömke, Miriam Reinhard, Chloé Loiseau, Claudia Ritter, Peter Sander, Sonia Borrell, Jimena Collantes Loo, Anchalee Avihingsanon, Joachim Gnokoro, Marcel Yotebieng, Matthias Egger, Sebastien Gagneux, Erik C Böttger
Whole genome sequencing allows rapid detection of drug-resistant Mycobacterium tuberculosis isolates. However, the availability of high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data has thus far been limited.We determined drug resistance profiles of 176 genetically diverse clinical M. tuberculosis isolates from Democratic Republic of the Congo, Ivory Coast, Peru, Thailand and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD BACTEC MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout...
February 4, 2019: Antimicrobial Agents and Chemotherapy
J A Reche-Sainz, M T Gracia García-Miguel, M A Pérez-Jacoiste
A 57-year-old man with miliary tuberculosis reported visual loss in his right eye, a month after starting a four-drug antituberculous treatment regimen. On exploration, an inferior segmental optic disc edema was objectived and it was attributed to ischemic aetiology. Ethambutol was withdrawn and 60mg of oral prednisone daily were given with a tapering dosage. One and a half months later, he presented a sudden loss of vision in his left eye. In fundoscopy, a papillary edema accompanied by a foveal neurosensory detachment was observed but with no more accompanying uveitic signs...
February 1, 2019: Archivos de la Sociedad Española de Oftalmología
Aditi Singh, Pallavi Somvanshi, Abhinav Grover
Arabinosyl tranferases (embA, embB, embC) are the key enzymes responsible for biogenesis of arabinan domain of arabinogalactan (AG) and lipoarabinomannan (LAM), two major heteropolysaccharide constituents of the peculiar mycobacterial cell envelope. EmbC is predominantly responsible for LAM synthesis and has been commonly associated with Ethambutol resistance. We have screened the FDA library against EmbC to reposition a drug better than Ethambutol with higher binding affinity to Embc. High throughput virtual screening followed by extra precision docking using Glide gave two best leads i...
February 1, 2019: Gene
Meltem Elitas
Antibiotic resistance has been one of the biggest threats to global health. Despite the available prevention and control strategies and efforts in developing new antibiotics, the need remains for effective approaches against antibiotic resistance. Efficient strategies to cope with antimicrobial resistance require a quantitative and deeper understanding of microbial behavior, which can be obtained using different techniques to provide the missing pieces of the current antibiotic-resistance puzzle. Microfluidic-microscopy techniques are among the most promising methods that contribute modernization of traditional assays in microbiology...
October 31, 2018: Micromachines
Orawan Tulyaprawat, Angkana Chaiprasert, Piriyaporn Chongtrakool, Kamol Suwannakarn, Popchai Ngamskulrungroj
Ethambutol (EMB) is the first-line antituberculosis drug and a potential supplementary agent for a treatment regimen of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). It has long been known that mutations in embCAB operon, encoding EMB target, arabinosyltransferase, confer resistance to EMB. Recently, ubiA was additionally reported to be specifically associated with high-level EMB resistance in Mycobacterium tuberculosis. However, such information on ubiA is very limited. This study aimed to investigate correlations between mutations in ubiA and phenotypic EMB resistance among EMB-resistant (EMBR ) M...
January 2019: Tuberculosis
N Sweetline Anne, B S M Ronald, T M A Senthil Kumar, A Thangavelu
This study was aimed out to explore the presence of drug resistance among M. tuberculosis and M. bovis isolates (n = 51) of bovine origin by conventional broth microdilution method and molecular methods. By broth microdilution method, 16 isolates were found to be resistant to isoniazid, 08 isolates were resistant to pyrazinamide, 09 isolates were resistant to rifampicin and 07 isolates were found to be resistant for ethambutol. Two isolates showed resistance to rifampicin and pyrazinamide, one isolate showed resistance to pyrazinamide and ethambutol and 03 isolates showed resistance to isoniazid and ethambutol...
January 2019: Tuberculosis
Ga-Young Ban, Yoon-Jeong Jeong, So-Hee Lee, Seung-Soo Shin, Yoo-Seob Shin, Hae-Sim Park, Seung-Hyun Kim, Young-Min Ye
BACKGROUND: Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment. OBJECTIVE: This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein. METHODS: This study was conducted as a prospective, observational cohort study...
February 2019: Respiratory Medicine
Andile H Ngwane, Ray-Dean Petersen, Bienyameen Baker, Ian Wiid, Ho Ning Wong, Richard K Haynes
The observations that the innate immune system employs copper to eliminate bacterial infection and that resistance to copper enhances virulence of Mycobacterium tuberculosis (Mtb) prompted us to examine the effects the anti-cancer agent elesclomol on Mtb. As a bis-thionohydrazide, elesclomol chelates with copper to form a copper complex in situ that via redox cycling of the metal ion greatly enhances oxidative stress in tumour cells. Here, we demonstrate that elesclomol is relatively potent against Mtb H37Rv with minimum inhibitory concentration of 10 μM (4 mg/L) and against multidrug resistant clinical isolates of Mtb, displays additive interactions with known tuberculosis drugs such as isoniazid and ethambutol, and a synergistic interaction with rifampicin...
January 14, 2019: IUBMB Life
Renata M Aguiar, Raquel A C Leão, Alejandro Mata, David Cantillo, C Oliver Kappe, Leandro S M Miranda, Rodrigo O M A de Souza
Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization...
January 29, 2019: Organic & Biomolecular Chemistry
Timothy M Walker, A Sarah Walker, Daniel J Wilson, Timothy E A Peto, Derrick W Crook, Farah Shamout, Tingting Zhu, David A Clifton
Motivation: Resistance co-occurrence within first-line anti-tuberculosis (TB) drugs is a common phenomenon. Existing methods based on genetic data analysis of Mycobacterium tuberculosis (MTB) have been able to predict resistance of MTB to individual drugs, but have not considered the resistance co-occurrence and cannot capture latent structure of genomic data that corresponds to lineages. Methods: We used a large cohort of TB patients from 16 countries across six continents where whole-genome sequences for each isolate and associated phenotype to anti-TB drugs were obtained using drug susceptibility testing recommended by the World Health Organization...
January 28, 2019: Bioinformatics
Ashutosh Kumar, Anwar Alam, Sonam Grover, Saurabh Pandey, Deeksha Tripathi, Monika Kumari, Mamta Rani, Aditi Singh, Yusuf Akhter, Nasreen Z Ehtesham, Seyed E Hasnain
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( M.tb ), takes one human life every 15 s globally. Disease relapse occurs due to incomplete clearance of the pathogen and reactivation of the antibiotic tolerant bacilli. M.tb , like other bacterial pathogens, creates an ecosystem of biofilm formed by several proteins including the cyclophilins. We show that the M.tb cyclophilin peptidyl-prolyl isomerase (PpiB), an essential gene, is involved in biofilm formation and tolerance to anti-mycobacterial drugs...
2019: NPJ Biofilms and Microbiomes
Jolie Krooks, Angela Weatherall, Stuart Markowitz
A 70-year-old, immunocompetent male presented with mildly painful and pruritic erythematous patches and vesicles on the right dorsal aspect of the distal middle finger present for four weeks. Other skin lesions or systemic symptoms were notably absent. The patient failed to respond to valacyclovir, topical triamcinolone acetonide ointment, trimethoprim-sulfamethoxazole, and cephalexin for presumptive diagnoses of recurrent herpetic whitlow, dyshidrotic eczema, and blistering distal dactylitis, respectively...
December 2018: Journal of Clinical and Aesthetic Dermatology
Justin Lee Loy, Gajapathiraju Chamarthi, Abhilash Koratala
Optic neuropathy is an uncommon finding in dialysis patients and has been associated with uremia, ischemia (arteritic and nonarteritic), drugs (isoniazid, ethambutol), infections (tuberculosis), and intracranial hypertension. Inflammatory optic neuritis associated with lupus is relatively rare, but clinicians need to be aware of this condition and obtain urgent ophthalmology consultation.
January 2019: Clinical Case Reports
Saad Habib, Kartikeya Rajdev, Sami Pervaiz, Abdul Hasan Siddiqui, Mohammed Azam, Michel Chalhoub
Non-tuberculous mycobacteria (NTM) are a significant cause of pulmonary infection worldwide and can be clinically challenging. Mycobacterium xenopi (M. xenopi) has low pathogenicity and usually requires either host immune impairment, as in the case of a human immunodeficiency virus infection, or a structural lung disease to cause a clinical disease. Comorbidities have an essential role in M. xenopi occurrence. Herein, we present a rare case of pulmonary cavitary disease caused by M. xenopi complicated by respiratory failure and superinfection in a patient with a chronic obstructive pulmonary disease...
October 29, 2018: Curēus
Sirus Amini, Sven Hoffner, Mohammadreza Allahyar Torkaman, Gholamreza Hamzehloo, Mohammad Javad Nasiri, Mahshid Salehi, Golnar Sami Kashkooli, Mohammadsadegh Shahraki, Maryam Mohsenpoor, Saman Soleimanpour, Raha Mir
Introduction Conventional indirect drug susceptibility testing (DST) of Mycobacterium tuberculosis with solid media is inexpensive and reliable, but time-consuming. This study was aimed to evaluate direct DST for testing of sputum samples without culture to significantly reduce the time required to detect multidrug-resistant tuberculosis (MDR-TB). METHODS: Direct and indirect DST of isoniazid (INH), rifampicin (RIF) and ethambutol (EMB) were performed on 334 sputum smear-positive specimens...
January 7, 2019: Journal of Global Antimicrobial Resistance
Yesari Eroksuz, Ersoy Baydar, Baris Otlu, Murat Dabak, Hatice Eroksuz, Burak Karabulut, Canan Akdeniz Incili, Mehmet Ozkan Timurkan
BACKGROUND: The diagnosis of previous cases of feline tuberculosis in Turkey has been made based solely on pathological changes without isolation of the causative agent. This case report details the first case of feline tuberculosis in Turkey for which the causative agent (Mycobacterium bovis) was confirmed with microbiological isolation, morphological evaluation, molecular (PCR) characterization and antibiotic sensitivity. CASE PRESENTATION: Systemic tuberculosis was diagnosed via postmortem examination of a 5-year-old stray male cat...
January 5, 2019: BMC Veterinary Research
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