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Tuberculosis, antimicrobial drug resistance

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https://www.readbyqxmd.com/read/28180188/imidazoles-induce-reactive-oxygen-species-in-mycobacterium-tuberculosis-which-is-not-associated-with-cell-death
#1
Heather A Howell Wescott, David M Roberts, Christian L Allebach, Rachel Kokoczka, Tanya Parish
Azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. We demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis. A marked increase in reactive oxygen species (ROS) was observed within imidazole-treated M...
January 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28174307/a-bioengineered-three-dimensional-cell-culture-platform-integrated-with-microfluidics-to-address-antimicrobial-resistance-in-tuberculosis
#2
Magdalena K Bielecka, Liku B Tezera, Robert Zmijan, Francis Drobniewski, Xunli Zhang, Suwan Jayasinghe, Paul Elkington
: Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28167588/prevalence-of-staphylococcus-aureus-nasal-carriage-in-human-immunodeficiency-virus-infected-and-uninfected-children-in-botswana-prevalence-and-risk-factors
#3
Michael J A Reid, Rebecca S B Fischer, Naledi Mannathoko, Charles Muthoga, Erin McHugh, Heather Essigmann, Eric L Brown, Andrew P Steenhoff
Staphylococcus aureus is an important cause of morbidity and mortality in children in sub-Saharan Africa (SSA). A major risk factor for staphylococcal infection is S. aureus colonization of the anterior nares. We sought to define risk factors for S. aureus carriage and characterize antimicrobial resistance patterns in children in Botswana. A cross-sectional study was conducted at two clinical sites in southern Botswana. Patients under 18 years of age underwent two nasal swabs and brief interviews, 4 weeks apart...
February 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28145487/the-antibacterial-activities-of-aditoprim-and-its-efficacy-in-the-treatment-of-swine-streptococcosis
#4
Guyue Cheng, Yamei Xu, Xudong Zhu, Shuyu Xie, Liye Wang, Lingli Huang, Haihong Hao, Zhenli Liu, Yuanhu Pan, Dongmei Chen, Yulian Wang, Zonghui Yuan
Aditoprim (ADP) has potential use as an antimicrobial agent in animals. However, its pharmacodynamic properties have not been systematically studied yet. In this study, the in vitro antibacterial activities of ADP and its main metabolites were assayed, and the in vivo antibacterial efficacy of ADP for the treatment of swine streptococcosis was evaluated. It was shown that Salmonella and Streptococcus from swine, Escherichia coli and Salmonella from chickens, E. coli, Streptococcus, Mannheimia, Pasteurella from calves, Streptococcus and Mannheimia from sheep, and E...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137234/mycobacterial-dna-replication-as-a-target-for-antituberculosis-drug-discovery
#5
Renata Płocińska, Małgorzata Korycka-Machała, Przemysław Płociński, Jarosław Dziadek
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28118738/design-of-potent-fluoro-substituted-chalcones-as-antimicrobial-agents
#6
Serdar Burmaoglu, Oztekin Algul, Arzu Gobek, Derya Aktas Anil, Mahmut Ulger, Busra Gul Erturk, Engin Kaplan, Aylin Dogen, Gönül Aslan
Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9-15, and 20-23) using a structure-activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and three common fungal strains. Three derivatives (3, 9, and 10) displayed significant antitubercular activity with IC50 values of ≤16,760...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28116106/engagement-of-the-private-pharmaceutical-sector-for-tb-control-rhetoric-or-reality
#7
Niranjan Konduri, Emily Delmotte, Edmund Rutta
BACKGROUND: Private-sector retail drug outlets are often the first point of contact for common health ailments, including tuberculosis (TB). Systematic reviews on public-private mix (PPM) interventions for TB did not perform in-depth reviews specifically on engaging retail drug outlets and related stakeholders in the pharmaceutical sector. Our objective was to better understand the extent to which the World Health Organization's (WHO) recommendation on engaging retail drug outlets has been translated into programmatic policy, strategy, and intervention in low- and middle-income countries...
2017: Journal of Pharmaceutical Policy and Practice
https://www.readbyqxmd.com/read/28080136/isoniazid-a-review-of-characteristics-properties-and-analytical-methods
#8
Guilherme Felipe Dos Santos Fernandes, Hérida Regina Nunes Salgado, Jean Leandro Dos Santos
Isoniazid is a synthetic antimicrobial and one of the most important first-line drugs used in the treatment of tuberculosis. Since it was introduced in the therapy in 1952, the drug remains at the front line of the antituberculosis treatment mainly due to its potency and high selectivity against Mycobacterium tuberculosis. Pharmaceutical analysis and therapeutic drug monitoring of isoniazid in both, pharmaceuticals and biological samples, plays an important role to comprehend aspects regarding to bioavailability, bioequivalence and therapeutic monitoring during patients following-up...
January 12, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/28074051/anti-folates-potentiate-bactericidal-effects-of-other-antimicrobial-agents
#9
Kun Li, Xu-de Wang, Shan-Shan Yang, Jing Gu, Jiao-Yu Deng, Xian-En Zhang
Synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. Previously, Vilchèze et al. found that, sulfamethoxazole (SMX) could potentiate the bacterialcidal activity of isoniazid (INH) and rifampin (RIF) in Mycobacterium tuberculosis. To test if this was also the case in other bacteria, the ability to potentiate bactericidal effect of RIF by SMX was evaluated in Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Mycobacterium smegmatis...
January 11, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28062229/new-tuberculosis-drug-leads-from-naturally-occurring-compounds
#10
REVIEW
Diana Quan, Gayathri Nagalingam, Richard Payne, James A Triccas
Tuberculosis (TB) continues to be a significant cause of mortality and morbidity worldwide. An estimated 2 billion individuals are infected with Mycobacterium tuberculosis and annually there are approximately 10 million new cases of clinical TB and 1.5 million deaths. Currently available drugs and vaccines have had no significant impact on TB control. In addition, the emergence of drug resistant TB is considered a public health crisis, with some strains now resistant to all available drugs. Unfortunately, the growing burden of antibiotic resistance is coupled with decreased effort in the development of new antibiotics...
January 3, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28057421/preparation-and-biological-evaluation-of-ethionamide-mesoporous-silicon-nanoparticles-against-mycobacterium-tuberculosis
#11
Nuno Vale, Alexandra Correia, Sara Silva, Patrícia Figueiredo, Ermei Mäkilä, Jarno Salonen, Jouni Hirvonen, Jorge Pedrosa, Hélder A Santos, Alexandra Fraga
Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28043505/collaboration-between-tuberculosis-control-programs-and-the-action-plan-for-tackling-antimicrobial-resistance-an-opportunity-in-the-eastern-mediterranean-region
#12
Rumina Hasan, Sadia Shakoor, Samiha Baghdadi, Alireza Mafi, Mohammad Aziz
OBJECTIVE/BACKGROUND: Over-the-counter availability of antibiotics together with poor access to diagnostics is recognised to promote antimicrobial resistance (AMR) including generation of drug-resistant tuberculosis (DR-TB). In accordance with the End TB Strategy target of ending TB epidemic by 2030, efforts to control DR-TB are ongoing in Eastern Mediterranean Region (EMR) countries, a number of which have well-established facilities for diagnostics, disease care and prevention as well as surveillance...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27997332/delivering-on-antimicrobial-resistance-agenda-not-possible-without-improving-fungal-diagnostic-capabilities
#13
David W Denning, David S Perlin, Eavan G Muldoon, Arnaldo Lopes Colombo, Arunaloke Chakrabarti, Malcolm D Richardson, Tania C Sorrell
Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients...
February 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/27993285/analysis-of-discrepant-results-between-the-genotype-%C3%A2-mtbdrplus-assay-and-an-antimicrobial-drug-susceptibility-test-for-isoniazid-resistant-tuberculosis
#14
Kyung-Wook Jo, Yoomi Yeo, Heungsup Sung, Mi-Na Kim, Tae Sun Shim
BACKGROUND: We investigated discrepant results determined using the Genotype(®)MTBDRplus assay and a conventional antimicrobial drug susceptibility test (ADST) for isoniazid (INH) resistance using sequencing analysis and analyzed the clinical course of patients with discrepant results. METHODS: Among 1373 MTBDRplus assays performed at our tertiary referral center in South Korea between August 2009 and December 2015, the results for 46 (3.4%) differed from those for ADST...
January 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/27956422/role-of-pyrazinamide-in-the-emergence-of-extensively-drug-resistant-tuberculosis-a-multi-strain-mathematical-model
#15
Mariam O Fofana, Sourya Shrestha, Gwenan M Knight, Ted Cohen, Richard G White, Frank Cobelens, David W Dowdy
Several infectious diseases of global importance - e.g. HIV, tuberculosis (TB) - require prolonged treatment with combination antimicrobial regimens, typically involving high-potency "core" agents coupled with additional "companion" drugs that protect against de novo emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are re-used in sequential (first-line, second-line, etc…) regimens. We used a multi-strain model of M. tuberculosis transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i...
December 12, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27936238/trehalose-6-phosphate-mediated-toxicity-determines-essentiality-of-otsb2-in-mycobacterium-tuberculosis-in-vitro-and-in-mice
#16
Jan Korte, Marina Alber, Carolina M Trujillo, Karl Syson, Hendrik Koliwer-Brandl, René Deenen, Karl Köhrer, Michael A DeJesus, Travis Hartman, William R Jacobs, Stephen Bornemann, Thomas R Ioerger, Sabine Ehrt, Rainer Kalscheuer
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27905500/targeting-intracellular-p-aminobenzoic-acid-production-potentiates-the-anti-tubercular-action-of-antifolates
#17
Joshua M Thiede, Shannon L Kordus, Breanna J Turman, Joseph A Buonomo, Courtney C Aldrich, Yusuke Minato, Anthony D Baughn
The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. Based on the observation that exogenously supplied p-aminobenzoic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase (DHPS), such as sulfonamides and p-aminosalicylic acid (PAS), we hypothesized that bacterial PABA biosynthesis contributes to intrinsic antifolate resistance...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856347/dna-topoisomerase-i-and-dna-gyrase-as-targets-for-tb-therapy
#18
REVIEW
Valakunja Nagaraja, Adwait A Godbole, Sara R Henderson, Anthony Maxwell
Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy...
November 14, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27810467/mycobacterium-tuberculosis-drug-resistance-testing-challenges-recent-developments-and-perspectives
#19
REVIEW
T Schön, P Miotto, C U Köser, M Viveiros, E Böttger, E Cambau
Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis...
March 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27784885/tuberculosis
#20
Madhukar Pai, Marcel A Behr, David Dowdy, Keertan Dheda, Maziar Divangahi, Catharina C Boehme, Ann Ginsberg, Soumya Swaminathan, Melvin Spigelman, Haileyesus Getahun, Dick Menzies, Mario Raviglione
Tuberculosis (TB) is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Although primarily a pulmonary pathogen, M. tuberculosis can cause disease in almost any part of the body. Infection with M. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent TB infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. Only active pulmonary TB is contagious...
October 27, 2016: Nature Reviews. Disease Primers
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