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Tuberculosis, antimicrobial drug resistance

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https://www.readbyqxmd.com/read/28080136/isoniazid-a-review-of-characteristics-properties-and-analytical-methods
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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 antibacterial 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 15, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
November 1, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27784885/tuberculosis
#13
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
https://www.readbyqxmd.com/read/27784282/mechanisms-of-first-line-antimicrobial-resistance-in-multi-drug-and-extensively-drug-resistant-strains-of-mycobacterium-tuberculosis-in-kwazulu-natal-south-africa
#14
Navisha Dookie, A Willem Sturm, Prashini Moodley
BACKGROUND: In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic. METHODS: In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tuberculosis in the KwaZulu-Natal province. RESULTS: Classical mutations were detected in the katG, inhA and embB genes associated with resistance to isoniazid and ethambutol...
October 26, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27738913/strategies-for-the-discovery-and-development-of-new-antibiotics-from-natural-products-three-case-studies
#15
Jennifer Herrmann, Tadeja Lukežič, Angela Kling, Sascha Baumann, Stephan Hüttel, Hrvoje Petković, Rolf Müller
Natural products continue to be a predominant source for new anti-infective agents. Research at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the Helmholtz Centre for Infection Research (HZI) is dedicated to the development of new lead structures against infectious diseases and, in particular, new antibiotics against hard-to-treat and multidrug-resistant bacterial pathogens. In this chapter, we introduce some of the concepts currently being employed in the field of antibiotic discovery...
2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/27699232/the-antifibrotic-drug-pirfenidone-promotes-pulmonary-cavitation-and-drug-resistance-in-a-mouse-model-of-chronic-tuberculosis
#16
Bintou A Ahidjo, Mariama C Maiga, Elizabeth A Ihms, Mamoudou Maiga, Alvaro A Ordonez, Laurene S Cheung, Sarah Beck, Bruno B Andrade, Sanjay Jain, William R Bishai
Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone's antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response...
September 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27671062/association-between-embb-codon-306-mutations-phenotypic-resistance-profiles-and-genotypic-characterization-in-clinical-mycobacterium-tuberculosis-isolates-from-hebei-china
#17
Yanan Li, Yuling Wang, Zhi Zhang, Huixia Gao, Haibin Wang, Jinfeng Cao, Shumin Zhang, Yuzhen Liu, Jianhua Lu, Zungui Xu, Erhei Dai
Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at embB codon 306 (embB306) have been proposed to be a potential marker for EMB resistance and a predictor of broad drug resistance in clinical Mycobacterium tuberculosis isolates. However, discordant findings about the association between embB306 mutations and EMB resistance were reported. Hebei Province is located in the Beijing-Tianjin-Hebei integration region in China; however, little information about the genetic diversity of the embB locus in this area is available...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27665179/investigation-of-c-5-alkynyl-alkynyloxy-or-hydroxymethyl-and-or-n-3-propynyl-substituted-pyrimidine-nucleoside-analogs-as-a-new-class-of-antimicrobial-agents
#18
Saurabh Garg, Neeraj Shakya, Naveen C Srivastav, Babita Agrawal, Dennis Y Kunimoto, Rakesh Kumar
The resurgence of mycobacterial infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6-10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30-33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (BCG) and Mycobacterium avium], gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) alone and in combination with existing drugs in in vitro assays...
November 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27623056/peptide-targeting-of-an-antibiotic-prodrug-toward-phagosome-entrapped-mycobacteria
#19
Mark P Pereira, Julie Shi, Shana O Kelley
Mycobacterial infections are difficult to treat due to the bacterium's slow growth, ability to reside in intracellular compartments within macrophages, and resistance mechanisms that limit the effectiveness of conventional antibiotics. Developing antibiotics that overcome these challenges is therefore critical to providing a pipeline of effective antimicrobial agents. Here, we describe the synthesis and testing of a unique peptide-drug conjugate that exhibits high levels of antimicrobial activity against M...
December 11, 2015: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27619156/antimycobacterial-activity-and-low-cytotoxicity-of-leaf-extracts-of-some-african-anacardiaceae-tree-species
#20
Prudence N Kabongo-Kayoka, Jacobus N Eloff, Chikwelu L Obi, Lyndy J McGaw
Treatment of tuberculosis (TB) is a challenge because of multidrug-resistant and extremely drug-resistant strains of Mycobacterium tuberculosis. Plant species contain antimicrobial compounds that may lead to new anti-TB drugs. Previous screening of some tree species from the Anacardiaceae family revealed the presence of antimicrobial activity, justifying further investigations. Leaf extracts of 15 Anacardiaceae tree species were screened for antimycobacterial activity using a twofold serial microdilution assay against the pathogenic Mycobacterium bovis and multidrug resistant M...
December 2016: Phytotherapy Research: PTR
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