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XDR tuberculosis

Cynthia Wong, Ngan P Ha, Michal E Pawlowski, Edward A Graviss, Tomasz S Tkaczyk
While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB...
September 28, 2016: Tuberculosis
Amber Kunkel, Frank G Cobelens, Ted Cohen
BACKGROUND: New drugs for the treatment of tuberculosis (TB) are becoming available for the first time in over 40 y. Optimal strategies for introducing these drugs have not yet been established. The objective of this study was to compare different strategies for introducing the new TB drug bedaquiline based on patients' resistance patterns. METHODS AND FINDINGS: We created a Markov decision model to follow a hypothetical cohort of multidrug-resistant (MDR) TB patients under different bedaquiline use strategies...
October 2016: PLoS Medicine
R Kumar, R Garg, S Kant, S K Verma, R A S Kushwaha, S Kumar, A Jain
OBJECTIVE: To study the drug resistance profile of patients with suspected multidrug-resistant tuberculosis (MDR-TB). MATERIAL AND METHODS: This was a prospective study conducted among patients with suspected MDR-TB attending the Department of Respiratory Medicine, King George's Medical University, Lucknow, India, from August 2014 to April 2015. Sputum samples obtained from 50 such patients were subjected to drug susceptibility testing against first- and second-line drugs...
October 2016: International Journal of Tuberculosis and Lung Disease
Ida Pam Ombura, Noel Onyango, Susan Odera, Florence Mutua, Joshua Nyagol
BACKGROUND: Although prevention and control of spread of multi-drug resistant tuberculosis strains is a global challenge, there is paucity of data on the prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya. The present study assessed patients' characteristics and prevalence of drug resistant TB in sputa smear positive TB patients presenting to Coast Provincial General Hospital (CPGH) in Mombasa, Kenya. METHODS: Drug resistance was evaluated in 258 randomly selected sputa smear TB positive cases between the periods of November 2011 to February 2012 at the CPGH-Mombasa...
2016: PloS One
Jorge Cervantes
Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind. A quintessential social disease, TB remains one of the world's deadliest communicable diseases, with still a high mortality and burden of disease. Social representations of TB focus on aspects associated to feelings and manifestations awakened by the disease, sometimes reinforcing stigmas and prejudices about the way of perceiving TB. TB is a historic disease now reborn with a deeper social stigma. Despite the modest reduction in TB incidence worldwide, its incidence is still rising in certain crisis-affected populations like refugees, and in those bearing high prevalence of HIV, persisting poverty, especially in the developing world...
October 2016: Respiratory Medicine
Ira Shah, Forum Shah
BACKGROUND: The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. AIM: To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. METHODS: A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B...
August 9, 2016: Paediatrics and International Child Health
Laura Pérez-Lago, Miguel Martínez-Lirola, Sergio García, Marta Herranz, Igor Mokrousov, Iñaki Comas, Llúcia Martínez, Emilio Bouza, Darío García de Viedma
Current migratory movements require new strategies for rapid tracking of the transmission of high-risk imported Mycobacterium tuberculosis strains. Whole genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design polymerase-chain-reaction assays (PCRs) to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally in separate institutions...
September 28, 2016: Journal of Clinical Microbiology
Didi Bang, Siri Rytcher Andersen, Edita Vasiliauskienė, Erik Michael Rasmussen
The emergence of extensively drug-resistant tuberculosis (XDR-TB) hampers infection control. To assess the performance of an extended rapid novel molecular analysis for the detection of resistance conferring mutations to fluoroquinolones (gyrA, gyrB genes) and aminoglycosides/cyclic peptides (16S rRNA rrs gene, eis promotor region) compared to phenotypic susceptibility and sequencing, 43 multidrug-resistant (MDR) and 10 susceptible clinical isolates were analyzed. Results were compared to a previous version...
August 31, 2016: Diagnostic Microbiology and Infectious Disease
Dulce Maria Juarez-Eusebio, Daniela Munro-Rojas, Raquel Muñiz-Salazar, Rafael Laniado-Laborín, Jose Armando Martinez-Guarneros, Carlos A Flores-López, Roberto Zenteno-Cuevas
Mexico is one of the most important contributors of multidrug resistance tuberculosis (MDR-TB) in Latin-America, however little is known about the molecular characteristics of these strains. For this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of Mexico with high prevalence of drug resistant tuberculosis. Clinical isolates from individuals with confirmed MDR-TB were genotyped using MIRU-VNTR 12 loci...
September 13, 2016: Infection, Genetics and Evolution
T Maitre, A Aubry, V Jarlier, J Robert, N Veziris
The emergence of drug-resistant tuberculosis (TB) compromises global tuberculosis control. The incidence of multidrug-resistant strains (MDR) defined as resistant to the two main antituberculosis drugs, rifampicin and isoniazid, was raised in the 1990s. Ten percent of these strains have developed additional resistance to the main second-line antituberculosis drugs: fluoroquinolones and aminoglycosides. These strains are defined as extensively drug-resistant (XDR). The prognosis of MDR-TB and XDR-TB is poor due to limited therapeutic resources...
September 13, 2016: Médecine et Maladies Infectieuses
G J Fox, H S Schaaf, A Mandalakas, E Chiappini, A Zumla, B J Marais
Prevention of multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is a top priority for global TB control, given the need to limit epidemic spread and considering the high cost, toxicity and poor treatment outcomes with available therapies. We performed a systematic literature review to evaluate the evidence for strategies to reduce MDR/XDR-TB transmission and disease progression. Rapid detection and timely initiation of effective treatment is critical to rendering MDR/XDR-TB cases non-infectious...
August 31, 2016: Clinical Microbiology and Infection
Leyla Sahebi, Khalil Ansarin, Parviz Mohajeri, Majid Khalili, Amir Monfaredan, Safar Farajnia, Simin Khayyat Zadeh
BACKGROUND: Tuberculosis (TB) is the leading cause of morbidity and mortality among chronic infectious diseases. OBJECTIVE: The goal of this cross-sectional study (2011-2013;2013) was to examine the patterns of TB drug resistance among HIV-negative pulmonary TB patients in regions near the Iranian border. METHOD: To this end, MTB isolates were harvested from 300 HIV-negative, pulmonary smear-positive TB patients from the northwest and west Iranian border provinces...
2016: Open Respiratory Medicine Journal
Behnoush Hajian, Eric Scocchera, Santosh Keshipeddy, Narendran G-Dayanandan, Carolyn Shoen, Jolanta Krucinska, Stephanie Reeve, Michael Cynamon, Amy C Anderson, Dennis L Wright
Mycobacterium tuberculosis continues to cause widespread, life-threatening disease. In the last decade, this threat has grown dramatically as multi- and extensively-drug resistant (MDR and XDR) bacteria have spread globally and the number of agents that effectively treat these infections is significantly reduced. We have been developing the propargyl-linked antifolates (PLAs) as potent inhibitors of the essential enzyme dihydrofolate reductase (DHFR) from bacteria and recently found that charged PLAs with partial zwitterionic character showed improved mycobacterial cell permeability...
2016: PloS One
Sophia B Georghiou, Marva Seifert, Shou-Yean Lin, Donald Catanzaro, Richard S Garfein, Roberta L Jackson, Valeriu Crudu, Camilla Rodrigues, Thomas C Victor, Antonino Catanzaro, Timothy C Rodwell
BACKGROUND: Rapid molecular diagnostics, with their ability to quickly identify genetic mutations associated with drug resistance in Mycobacterium tuberculosis clinical specimens, have great potential as tools to control multi- and extensively drug-resistant tuberculosis (M/XDR-TB). The Qiagen PyroMark Q96 ID system is a commercially available pyrosequencing (PSQ) platform that has been validated for rapid M/XDR-TB diagnosis. However, the details of the assay's diagnostic and technical performance have yet to be thoroughly investigated in diverse clinical environments...
2016: BMC Infectious Diseases
Kavita Chaudhari, Sanjay Surana, Pritam Jain, Harun M Patel
New classes of drugs are needed to treat tuberculosis (TB) in order to combat the emergence of resistance (MDR and XDR) to existing agents and shorten the duration of therapy. Mycobacterial DNA gyrase B subunit has been identified to be one of the potentially under exploited drug targets in the field of antitubercular drug discovery. In the present review, we discussed the synthesis, structural optimization and docking study of effective potent DNA gyrase inhibitor against M. tuberculosis, with improved properties such as enhanced activity against MDR strains, reduced toxicity...
August 20, 2016: European Journal of Medicinal Chemistry
Sanghyuk S Shin, Chawangwa Modongo, Rosanna Boyd, Cynthia Caiphus, Lesego Kuate, Botshelo Kgwaadira, Nicola M Zetola
BACKGROUND: Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV-infected and HIV-uninfected patients in Botswana after ART expansion. METHODS: We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients...
August 19, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Kiatichai Faksri, Jun Hao Tan, Areeya Disratthakit, Eryu Xia, Therdsak Prammananan, Prapat Suriyaphol, Chiea Chuen Khor, Yik-Ying Teo, Rick Twee-Hee Ong, Angkana Chaiprasert
Multi-drug and extensively drug-resistant tuberculosis (MDR and XDR-TB) are problems that threaten public health worldwide. Only some genetic markers associated with drug-resistant TB are known. Whole-genome sequencing (WGS) is a promising tool for distinguishing between re-infection and persistent infection in isolates taken at different times from a single patient, but has not yet been applied in MDR and XDR-TB. We aim to detect genetic markers associated with drug resistance and distinguish between reinfection and persistent infection from MDR and XDR-TB patients based on WGS analysis...
2016: PloS One
Miraj Ahmed, Anupam Mishra, Kamal Kumar Sawlani, Veerendra Verma, Rajiv Garg, Hitendra Prakash Singh, Sunil Kumar
The Global tuberculosis control is challenged with a growing resistance to antitubercular treatment (ATT) culminating in resistant (MDR/XDR) strains; an important factor being premature withdrawal of streptomycin owing to its morbidity particularly nephrotoxicity and cochleotoxicity as guidelines for their prevention exist. An attempt is made here to address the least recognized and most debilitating vestibular toxic effects of streptomycin and defining a vestibular-protocol for its early detection and progression...
September 2016: Indian Journal of Otolaryngology and Head and Neck Surgery
Hoa Binh Nguyen, Nhung Viet Nguyen, Huong Thi Giang Tran, Hai Viet Nguyen, Quyen Thi Tu Bui
INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. METHODS: Eighty clusters of TB cases were selected using a probability-proportion-to-size approach...
April 2016: Western Pacific Surveillance and Response Journal: WPSAR
Andrés Palencia, Xianfeng Li, Wei Bu, Wai Choi, Charles Z Ding, Eric E Easom, Lisa Feng, Vincent Hernandez, Paul Houston, Liang Liu, Maliwan Meewan, Manisha Mohan, Fernando L Rock, Holly Sexton, Suoming Zhang, Yasheen Zhou, Baojie Wan, Yuehong Wang, Scott G Franzblau, Lisa Woolhiser, Veronica Gruppo, Anne J Lenaerts, Theresa O'Malley, Tanya Parish, Christopher B Cooper, M Gerard Waters, Zhenkun Ma, Thomas R Ioerger, James C Sacchettini, Joaquín Rullas, Iñigo Angulo-Barturen, Esther Pérez-Herrán, Alfonso Mendoza, David Barros, Stephen Cusack, Jacob J Plattner, M R K Alley
The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB...
October 2016: Antimicrobial Agents and Chemotherapy
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