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https://www.readbyqxmd.com/read/29240876/machine-learning-for-classifying-tuberculosis-drug-resistance-from-dna-sequencing-data
#1
Yang Yang, Katherine E Niehaus, Timothy M Walker, Zamin Iqbal, A Sarah Walker, Daniel J Wilson, Tim E Peto, Derrick W Crook, E Grace Smith, Tingting Zhu, David A Clifton
Motivation: Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Methods: Given the availability of DNA sequencing data from MTB, we developed machine learning models for a cohort of 1839 UK bacterial isolates to classify MTB resistance against eight anti-TB drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, ciprofloxacin, moxifloxacin, ofloxacin, streptomycin) and to classify multi-drug resistance...
December 12, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29229639/whole-cell-screen-of-fragment-library-identifies-gut-microbiota-metabolite-indole-propionic-acid-as-antitubercular
#2
Dereje A Negatu, Joe J J Liu, Matthew Zimmerman, Firat Kaya, Véronique Dartois, Courtney C Aldrich, Martin Gengenbacher, Thomas Dick
Several key tuberculosis drugs including pyrazinamide, with a molecular weight of 123.1 g/mol, are smaller than the usual drug like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular weights centered around 400-500 g/mol. Fragment (molecular weight < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1000 fragments, present in the Maybridge Ro3 library, for whole cell activity against Mycobacterium tuberculosis Twenty-nine primary hits showed dose-dependent growth inhibition equal or better than pyrazinamide...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29204099/tuberculosis-infection-in-children-with-proteinuria-nephrotic-syndrome
#3
Hanna Szymanik-Grzelak, Elżbieta Kuźma-Mroczkowska, Piotr Skrzypczyk, Teresa Bielecka, Iwona Kotula, Małgorzata Pańczyk-Tomaszewska
Children with nephrotic syndrome (NS) are at greater risk of infections than the general population, due to immunodeficiency in the course of the disease and the treatment. In this study we present 4 children (2 girls, 2 boys), mean age 7.6 ±5.1 years, with NS/proteinuria and latent tuberculosis in 3 children and lymph node tuberculosis in 1 child. The reasons for testing these children for tuberculosis (TB) were the evaluation of the epidemiological status before treatment with corticosteroids (GCS), leukopenia and the relapse of NS, and non-nephrotic proteinuria...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/29203492/extreme-drug-tolerance-of-mycobacterium-tuberculosis-in-caseum
#4
Jansy P Sarathy, Laura E Via, Danielle Weiner, Landry Blanc, Helena Boshoff, Eliseo A Eugenin, Clifton E Barry, Véronique A Dartois
Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence and drug tolerance are among the factors driving the long therapy duration. Assays to measure in situ drug susceptibility of Mycobacterium tuberculosis (Mtb) bacteria in pulmonary lesions are needed if we are to discover new fast acting regimens and address the global TB threat. Here we take a first step towards this goal and describe an ex vivo assay developed to measure the cidal activity of anti-TB drugs against Mtb bacilli present in cavity caseum, obtained from rabbits with active TB...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203478/limited-effect-of-later-generation-fluoroquinolones-in-the-treatment-of-ofloxacin-resistant-and-moxifloxacin-susceptible-multidrug-resistant-tuberculosis
#5
Hyun Lee, Soohyun Ahn, Na Young Hwang, Kyeongman Jeon, O Jung Kwon, Hee Jae Huh, Nam Yong Lee, Chang-Ki Kim, Won-Jung Koh
Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant/moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29197297/use-of-chemometrics-to-compare-nir-and-hplc-for-the-simultaneous-determination-of-drug-levels-in-fixed-dose-combination-tablets-employed-in-tuberculosis-treatment
#6
Kelly Sivocy Sampaio Teixeira, Said Gonçalves da Cruz Fonseca, Luís Carlos Brigido de Moura, Mario Luís Ribeiro de Moura, Márcia Herminia Pinheiro Borges, Euzébio Guimaraes Barbosa, Túlio Flávio Accioly De Lima E Moura
The World Health Organization recommends that TB treatment be administered using combination therapy. The methodologies for quantifying simultaneously associated drugs are highly complex, being costly, extremely time consuming and producing chemical residues harmful to the environment. The need to seek alternative techniques that minimize these drawbacks is widely discussed in the pharmaceutical industry. Therefore, the objective of this study was to develop and validate a multivariate calibration model in association with the near infrared spectroscopy technique (NIR) for the simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol...
November 23, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29189762/synthesis-and-in-vitro-antimycobacterial-activity-of-novel-n-arylpiperazines-containing-an-ethane-1-2-diyl-connecting-chain
#7
Tomáš Goněc, Ivan Malík, Jozef Csöllei, Josef Jampílek, Jiřina Stolaříková, Ivan Solovič, Peter Mikuš, Stanislava Keltošová, Peter Kollár, Jim O'Mahony, Aidan Coffey
Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a-h) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log kw values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (ϕM), varied from 2...
November 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29188776/metal-complexes-of-isonicotinylhydrazide-and-their-antitubercular-activity
#8
Mohsin Ali, Mansoor Ahmed, Saleem Hafiz, Mustafa Kamal, Majid Mumtaz, Muhammad Hanif, Khalid Mohammed Khan
The development and spreading of Multi Drug Resistant TB strains is hampering endeavours for the control and administration of tuberculosis (TB). The expansion episodes of multi-medication safe strains of Mycobacterium tuberculosis against first and second line antituberculosis drugs on one side and the unfavourable effects of these drugs on the other side has led the enthusiasm of researcher towards the synthesis of metal complexes of various medication. This approach is born with the expectation of finding new antituberculous operators without or least reactions as well as being active against the resistant strains of Mycobacterium tuberculosis...
November 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29188195/comparative-genomic-analysis-of-two-clonally-related-multidrug-resistant-mycobacterium-tuberculosis-by-single-molecule-real-time-sequencing
#9
Kenneth Siu-Sing Leung, Gilman Kit-Hang Siu, Kingsley King-Gee Tam, Sabrina Wai-Chi To, Rahim Rajwani, Pak-Leung Ho, Samson Sai-Yin Wong, Wei W Zhao, Oliver Chiu-Kit Ma, Wing-Cheong Yam
Background: Multidrug-resistant tuberculosis (MDR-TB) is posing a major threat to global TB control. In this study, we focused on two consecutive MDR-TB isolated from the same patient before and after the initiation of anti-TB treatment. To better understand the genomic characteristics of MDR-TB, Single Molecule Real-Time (SMRT) Sequencing and comparative genomic analyses was performed to identify mutations that contributed to the stepwise development of drug resistance and growth fitness in MDR-TB under in vivo challenge of anti-TB drugs...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29180526/on-the-antibacterial-and-sterilizing-effect-of-benzylpenicillin-in-tuberculosis
#10
Devyani Deshpande, Shashikant Srivastava, Paula Bendet, Katherine R Martin, Kayle N Cirrincione, Pooi S Lee, Jotam G Pasipanodya, Keertan Dheda, Tawanda Gumbo
The modern chemotherapy era started with Fleming's discovery of benzylpenicillin. He demonstrated that benzylpenicillin did not kill Mycobacterium tuberculosis (Mtb) Here, we found that >64 mg/L of static benzylpenicillin concentrations killed 1.16-1.43 log10 CFU/mL below starting inoculum of extracellular and intracellular Mtb over 7 days. When we added the β-lactamase-inhibitor avibactam, benzylpenicillin maximal kill (Emax) of either extracellular log-phase growth Mtb was 6.80±0.45 log10 CFU/mL at an EC50 of 15...
November 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29179699/gastrointestinal-tuberculosis-following-renal-transplantation-accompanied-with-septic-shock-and-acute-respiratory-distress-syndrome-a-survival-case-presentation
#11
Andrea Cikova, Diana Vavrincova-Yaghi, Peter Vavrinec, Anna Dobisova, Andrea Gebhardtova, Zora Flassikova, Mark A Seelen, Robert H Henning, Aktham Yaghi
BACKGROUND: Post-transplant tuberculosis (PTTB) is a serious opportunistic infection in renal graft recipients with a 30-70 fold higher incidence compared to the general population. PTTB occurs most frequently within the first years after transplantation, manifesting as pulmonary or disseminated TB. Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB and may show delayed onset in renal transplant recipients due to the use of lower doses of immunosuppressants...
November 28, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29175704/synthesis-and-mechanistic-investigation-of-iron-ii-complexes-of-isoniazid-and-derivatives-as-a-redox-mediated-activation-strategy-for-anti-tuberculosis-therapy
#12
Julie Laborde, Céline Deraeve, Francisca Gilmara de Mesquita Vieira, Alix Sournia-Saquet, Lionel Rechignat, Anne Drumond Villela, Bruno Lopes Abbadi, Fernanda Souza Macchi, Kenia Pissinati, Cristiano V Bizarro, Pablo Machado, Luiz Augusto Basso, Geneviève Pratviel, Luiz Gonzaga de França Lopes, Eduardo Henrique Silva Sousa, Vania Bernardes-Génisson
The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB) represents a major threat to global health. Isoniazid (INH) is a prodrug used in the first-line treatment of tuberculosis. It undergoes oxidation by a catalase-peroxidase KatG, leading to generation of an isonicotinoyl radical that reacts with NAD(H) forming the INH-NADH adduct as the active metabolite. A redox-mediated activation of isoniazid using an iron metal complex was previously proposed as a strategy to overcome isoniazid resistance due to KatG mutations...
November 21, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29173450/outcomes-of-pulmonary-tuberculosis-in-patients-with-discordant-phenotypic-isoniazid-resistance-testing
#13
Sukyeon Kim, Hyun Lee, Hye Yun Park, Kyeongman Jeon, Hee Jae Huh, Nam Yong Lee, Byeong-Ho Jeong
INTRODUCTION: The discrepancy rates of drug susceptibility testing (DST) results between solid and liquid media have been reported to range from 2.4 to 7.4% for isoniazid. Most isolate with isoniazid DST discrepancies between solid and liquid media test as susceptible on solid medium and resistant in liquid medium, however, the optimal management of patients with discordant testing is unknown. This study was conducted to evaluate the effect of treatment regimen on treatment outcomes when patients with rifampicin-susceptible pulmonary tuberculosis have isoniazid resistance (INH-R) in liquid medium but isoniazid susceptibility (INH-S) on solid medium...
December 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29171560/mutation-analysis-for-detection-of-drug-resistance-in-mycobacterium-tuberculosis-isolates-from-khyber-pakhtunkhwa-pakistan
#14
Bashir Ahmad, Muhammad Idrees, Kafeel Ahmad, Shumaila Bashir, Sajjad Ahmad, Huang Lin-Fang
OBJECTIVE: To examine the frequency and distribution of mutations in the 'hot spot regions' of drug-resistant genes. METHODS: The study was conducted at Provincial Tuberculosis Reference Laboratory, Peshawar, Pakistan, from April 2015 to March 2016, and comprised sputum samples. Isolates were tested for drug susceptibility and resistant isolates were investigated for mutations analysis in the 'hot spot regions' of rpoB, rpsL, embB, pncA, gyrA and gyrB genes. RESULTS: Of the 163 isolates, 47(28...
November 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/29150181/corrigendum-to-chloroquine-enhances-the-antimycobacterial-activity-of-isoniazid-and-pyrazinamide-by-reversing-inflammation-induced-macrophage-efflux-the-international-journal-of-antimicrobial-agents-50-1-2017-55-62
#15
U Matt, P Selchow, M Dal Molin, S Strommer, O Sharif, K Schilcher, F Andreoni, A Stenzinger, A S Zinkernagel, M Zeitlinger, P Sander, J Nemeth
No abstract text is available yet for this article.
November 14, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29149917/treatment-outcome-with-a-short-multidrug-resistant-tuberculosis-regimen-in-nine-african-countries
#16
A Trébucq, V Schwoebel, Z Kashongwe, A Bakayoko, C Kuaban, J Noeske, S Hassane, B Souleymane, A Piubello, F Ciza, V Fikouma, M Gasana, M Ouedraogo, M Gninafon, A Van Deun, D M Cirillo, K G Koura, H L Rieder
<h2>SETTING:</h2>Nine countries in West and Central Africa.<h2>OBJECTIVE:</h2>To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs.<h2>DESIGN:</h2>Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months...
November 17, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29142798/verification-of-diagnosis-in-tuberculosis-a-case-report-and-discussion
#17
Amanda M Dave, Abed Adelrahman, Vishist Mehta, Stephen Cavalieri, Renuga Vivekanadan
Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days' duration. Cultures were positive for acid fast bacteria and negative for fungi...
September 3, 2017: Curēus
https://www.readbyqxmd.com/read/29137108/tuberculosis-presenting-as-isolated-bronchonodal-fistula-in-a-patient-with-systemic-lupus-erythematosus-case-report
#18
Kyungsoo Bae, Kyung Nyeo Jeon, Ho Cheol Kim, Young Sun Suh, Gi Dong Lee, Ju-Young Kim, Dae Hyun Song
RATIONALE: Lymph node is a preferred site for extrapulmonary tuberculosis (TB). In the thorax, mediastinal tuberculous lymph nodes can erode adjacent structures such as heart, aorta, and esophagus, forming fistula, and causing fatal consequences. However, tuberculous bronchonodal fistula as a complication of lymph node TB in adults is rarely known in terms of imaging or clinical findings. Here, a case of isolated tuberculous bronchonodal fistula appearing as the first presentation of TB in a 74-year-old male with systemic lupus erythematosus (SLE) is reported...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29133558/pharmacokinetics-and-drug-drug-interactions-of-lopinavir-ritonavir-administered-with-first-and-second-line-antituberculosis-drugs-in-hiv-infected-children-treated-for-multidrug-resistant-tuberculosis
#19
Louvina E van der Laan, Anthony J Garcia-Prats, H Simon Schaaf, Tjokosela Tikiso, Lubbe Wiesner, Mine de Kock, Jana Winckler, Jennifer Norman, Helen McIlleron, Paolo Denti, Anneke C Hesseling
Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29130630/a-structure-based-strategy-toward-the-development-of-novel-candidates-for-antimycobacterial-activity-synthesis-biological-evaluation-and-docking-study
#20
Linhu Li, Yuanyuan Jin, Bin Wang, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Jun Zhang, Yu Lu
Bacterial resistance to most of the available antibiotics has stimulated the discovery of novel efficacious antibacterial agents. Bedaquiline is first of its type that has been specifically introduced for the management of MDR-TB in combination with other drugs. In the current study, a series of isoniazid/ethambutol/pyrazinamide -quinoline conjugates based on the structures of Bedaquiline were designed and synthesized. Biological activity tests revealed that some of isoniazid/ethambutol-quinoline conjugates have useful antibiotic activity against MTB H37Rv (MIC: 2...
November 11, 2017: Chemical Biology & Drug Design
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