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S M Ramirez-Busby, T C Rodwell, L Fink, D Catanzaro, R L Jackson, M Pettigrove, A Catanzaro, F Valafar
Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA molecular diagnostics in M/XDR TB cases. A set of 296, mostly XDR, clinical M. tuberculosis isolates from four countries were subjected to DST for eight drugs, confirmatory Wayne's assay, and whole-genome sequencing...
June 19, 2017: Scientific Reports
#2
N Bablishvili, N Tukvadze, E Shashkina, B Mathema, N R Gandhi, H M Blumberg, R R Kempker
SETTING: The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB).OBJECTIVE: To evaluate whether the detection of mutations in gyrB and eis genes increased the sensitivity of detecting phenotypic resistance to ofloxacin and kanamycin or capreomycin as compared to use of the first generation MTBDRsl assay alone which evaluates for mutations in gyrA and rrs genes.DESIGN: A retrospective study of storedMycobacterium tuberculosis isolates. All isolates underwent DNA sequencing of resistance determining regions...
June 19, 2017: Antimicrobial Agents and Chemotherapy
#3
Niccolò Riccardi, Filippo Del Puente, Federica Magnè, Lucia Taramasso, Antonio Di Biagio
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDR-TB). Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; moreover, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for treatment of MDR-TB. BDQ is a diarylquinoline anti-mycobacterial drug, active regardless the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location...
June 19, 2017: Recent Patents on Anti-infective Drug Discovery
#4
M-S Hong, Y Kim, E-J Cho, J-S Lee, H-K Kwak, J-H Kim, C-T Kim, J-S Cho, S-K Park, D Jeon, Y-I Choi, H Lee, S-Y Eum
Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB...
June 15, 2017: European Journal of Clinical Microbiology & Infectious Diseases
#5
Aravind Swaminathan, Philipp du Cros, James A Seddon, Shamsiya Mirgayosieva, Rajabov Asladdin, Zulfiya Dusmatova
BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy...
June 12, 2017: BMC Infectious Diseases
#6
REVIEW
Vajinder Kumar, Sanjay Patel, Rahul Jain
Tuberculosis (TB), one of the deadliest diseases is shattering the health and socioeconomic status of the society. The emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains has provided unprecedented lethal character to TB. The development of MDR and XDR strains of TB results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. Because of the development of rapid resistance by Mycobacterium tuberculosis, researchers are confronted with serious challenges in combating TB...
June 9, 2017: Medicinal Research Reviews
#7
Fanny Quenard, Pierre Edouard Fournier, Michel Drancourt, Philippe Brouqui
Second-line injectable antituberculosis drugs (aminoglycosides and capreomycin) are the main drugs used in the management of resistant tuberculosis. Their preserved efficacy in the case of multi-drug-resistant bacillus is counterbalanced by frequent adverse events. Adverse events are linked to the drugs themselves and to the recommended 8-month period of parenteral administration. In numerous countries facing a high incidence of multi-drug-resistant tuberculosis, treatment is administered by intramuscular injection...
June 5, 2017: International Journal of Antimicrobial Agents
#8
REVIEW
Guilherme Felipe Dos Santos Fernandes, Chung Man Chin, Jean Leandro Dos Santos
Tuberculosis (TB), a disease caused mainly by the Mycobacterium tuberculosis (Mtb), is according to the World Health Organization (WHO) the infectious disease responsible for the highest number of deaths worldwide. The increased number of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. The scenario of drug discovery becomes alarming when it is considered that the number of new drugs does not increase proportionally to the emergence of drug resistance...
June 1, 2017: Pharmaceuticals
#9
Jihee Jung, Yangjin Jegal, Moran Ki, Young Jeon Shin, Cheon Tae Kim, Tae Sun Shim, Nackmoon Sung
Although several reports about drug-resistant tuberculosis (TB) in North Korea have been published, a nationwide surveillance on this disease remains to be performed. This study aims to analyze the drug resistance patterns of Mycobacterium tuberculosis among the patients in the sanatoria of North Korea, especially during the period when second-line drugs (SLDs) had not yet been officially supplied to this country. The Eugene Bell Foundation (EBF) transferred 947 sputum specimens obtained from 667 patients from 2007 to 2009 to the Clinical Research Center, Masan National Tuberculosis Hospital (MNTH), South Korea...
July 2017: Journal of Korean Medical Science
#10
Beibei Wu, Le Zhang, Zhengwei Liu, Haibo He, Aizhen Pan, Fei Wang, Mingwu Zhang, Bin Chen, Zuhong Lu, Songhua Chen, Xiaomeng Wang
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) hinder the progress of TB control. OBJECTIVE: To track the trend of drug-resistant tuberculosis (DR-TB) prevalence in Zhejiang Province from 1999 to 2013, and identify risk factors of resistance to second-line drugs among MDR-TB patients. DESIGN: Four DR-TB surveys had been done in Zhejiang Province in 1999, 2004, 2008 and 2013 through questionnaires, in which demographic and epidemiological items were included...
2017: Global Health Action
#11
Salima Qamar, Joveria Q Farooqi, Kausar Jabeen, Rumina Hasan
BACKGROUND: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene), we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance...
April 2017: International Journal of Mycobacteriology
#12
Hafij Al Mahmud, Hoonhee Seo, Sukyung Kim, Md Imtiazul Islam, Kung-Woo Nam, Hyun-Deuk Cho, Ho-Yeon Song
BACKGROUND: Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. METHODS: In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages...
May 25, 2017: BMC Complementary and Alternative Medicine
#13
Alireza Hadizadeh Tasbiti, Shamsi Yari, Mostafa Ghanei, Mohammad Ali Shokrgozar, Abolfazl Fateh, Ahmadreza Bahrmand
OBJECTIVES: Extensively drug-resistant tuberculosis (XDR-TB) is more expensive and difficult to treat than multidrug-resistant tuberculosis (MDR-TB), and outcomes for patients are much worse; therefore, it is important that clinicians understand the magnitude and distribution of XDR-TB. We conducted a retrospective study to compare the estimated incidence of and risk factors for M/XDR-TB with those of susceptible TB controls. METHODS: Sputum culture and drug susceptibility testing (DST) were performed in patients with known or suspected TB...
April 2017: Osong Public Health and Research Perspectives
#14
Thomas Maitre, Grégoire Petitjean, Aurélie Chauffour, Christine Bernard, Najoua El Helali, Vincent Jarlier, Florence Reibel, Pascal Chavanet, Alexandra Aubry, Nicolas Veziris
Background: : Moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis . Levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile. Objectives: : To compare the in vivo activity of levofloxacin and moxifloxacin against M. tuberculosis strains with various levels of fluoroquinolone resistance. Methods: BALB/c mice were intravenously infected with 10 6 M...
May 23, 2017: Journal of Antimicrobial Chemotherapy
#15
Aleksandr I Ilin, Murat E Kulmanov, Ilya S Korotetskiy, Rinat A Islamov, Gulshara K Akhmetova, Marina V Lankina, Oleg N Reva
Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187...
2017: Frontiers in Cellular and Infection Microbiology
#16
REVIEW
Amber Kunkel, Jennifer Furin, Ted Cohen
Global rollout of the new antituberculosis drug bedaquiline has been slow, in part reflecting concerns about spread of bedaquiline resistance. Acquired resistance to bedaquiline is especially likely in patients with extensively drug-resistant (XDR) tuberculosis. However, the very high mortality rates of patients with XDR not receiving bedaquiline, and promising cohort study results, suggest these patients also have greatest need for the drug. In this Personal View, we argue that resistance concerns should not forestall use of bedaquiline in patients with XDR tuberculosis...
May 19, 2017: Lancet Infectious Diseases
#17
Sergey E Borisov, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan-Willem Alffenaar, Andrey Maryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, Jose A Caminero, Isabel Carpena Martinez, Luigi Codecasa, Margareth Dalcolmo, Justin Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Alexey Filippov, Lina Davies Forsman, Mina Gaga, Julia-Amaranta Garcia-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Katerina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Juan Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Farokh Udwadia, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
#18
F Pérez-García, M J Ruiz-Serrano, P López Roa, Fermín Acosta, Laura Pérez-Lago, D García-De-Viedma, E Bouza
PURPOSE: Genotypic methods have considerably improved the diagnosis of multidrug-resistant (MDR) tuberculosis. One of these tests is Anyplex II MTB/MDR/XDR (Anyplex). Our aim was to evaluate the diagnostic performance of this multiplex PCR. METHODS: We conducted our study on 47 MDR tuberculosis and 14 pan-susceptible strains. We evaluated the ability of Anyplex to detect resistance mutations in rpoB (rifampin [RIF]), katG and inhA (isoniazid [INH]), gyrA (fluoroquinolones [FLQ]), and rrs and eis (aminoglycosides [AMG])...
May 13, 2017: Journal of Microbiological Methods
#19
Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis patients.
Natasha Van't Boveneind-Vrubleuskaya, Tatiana Seuruk, Kai van Hateren, Tridia van der Laan, Jos G W Kosterink, Tjip S van der Werf, Dick van Soolingen, Susan van den Hof, Alena Skrahina, Jan-Willem C Alffenaar
Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter to predict the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of treatment regimen at a dose of 15 mg/kg once daily...
May 15, 2017: Antimicrobial Agents and Chemotherapy
#20
Bright Varghese, Sahal Al-Hajoj
AbstractIn Saudi Arabia, there were no nationwide screening studies conducted so far to determine the aminoglycoside and fluoroquinolone resistance among multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first attempt in the country, a retrospective analysis has been conducted on a nationwide collection of 2,956 M. tuberculosis clinical isolates screened with phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates were subjected to second-line drug susceptibility testing, detection of mutations conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeat typing and spoligotyping...
May 2017: American Journal of Tropical Medicine and Hygiene
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