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multi drug resistant tuberculosis

Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 major TB drug including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming substantial portions of budgets allocated to national TB programmes in TB endemic countries, and is a major threat to healthcare workers who are already in short supply in resource-poor settings...
October 15, 2016: Clinical Microbiology and Infection
Diego G Ghiano, Agustina de la Iglesia, Nina Liu, Peter J Tonge, Héctor R Morbidoni, Guillermo R Labadie
A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis, being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms...
September 28, 2016: European Journal of Medicinal Chemistry
Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: 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
Gouranga Santra, Rudrajit Paul, Avik Karak, Somnath Mukhopadhay
A 22 year-old lady with multi-drug-resistant pulmonary tuberculosis was on Kanamycin, Cycloserine, Ethionamide, Pyrazinamide and Moxifloxacin since more than two months. She presented with muscle cramps and carpopedal spasm. Investigation revealed hypokalemia and metabolic alkalosis. She also had hypomagnesemia, hypochloremia and hypocalciuria. Serum urea and creatinine levels were normal. Patient was treated with intravenous and oral potassium chloride. Kanamycin was stopped. Metabolic alkalosis and hypokalemia improved gradually over one month...
May 2016: Journal of the Association of Physicians of India
Pravin Rathi, Pravir Gambhire
Abdomen is involved in 11% of patients with extra-pulmonary tuberculosis; The most common site of involvement is the ileocaecal region, other locations of involvement, in order of descending frequency, are the ascending colon, jejunum, appendix, duodenum, stomach, oesophagus, sigmoid colon, and rectum. Apart from the basic work up, Investigations like CT scan, EUS, Capsule endoscopy, Balloon enteroscopy, Ascitic fluid ADA, TB-PCR, GeneXpert, Laproscopy are being increasingly used to diagnose tuberculosis.Therapy with standard antituberculous drugs is usually highly effective for intestinal TB...
February 2016: Journal of the Association of Physicians of India
Sutapa Khatua, Abby M Geltemeyer, Anand Gourishankar
Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of Tuberculosis. During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing Mycobacterium Tuberculosis.TB is the second most common cause of death from infectious diseases after HIV/AIDS...
October 10, 2016: Pediatric Research
Daniel L Priebbenow, Lisa Barbaro, Jonathan B Baell
Multi-drug resistant tuberculosis (MDR-TB) is of growing global concern and threatens to undermine increasing efforts to control the worldwide spread of tuberculosis (TB). Bedaquiline has recently emerged as a new drug developed to specifically treat MDR-TB. Despite being highly effective as a result of its unique mode of action, bedaquiline has been associated with significant toxicities and as such, safety concerns are limiting its clinical use. In order to access pharmaceutical agents that exhibit an improved safety profile for the treatment of MDR-TB, new synthetic pathways to facilitate the preparation of bedaquiline and analogues thereof have been discovered...
October 12, 2016: Organic & Biomolecular Chemistry
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
Esther Del Olmo, Gloria M Molina-Salinas, Estela I Bini, Silvia González-Hernández, Luis A Bustos, Ricardo Escarcena, Brenda Marquina-Castillo, Dulce Mata-Espinosa, Jorge Barrios-Payán, Diego González-Ramírez, Salvador Said Fernández, Arturo San Feliciano, Rogelio Hernández-Pando
BACKGROUND AND AIMS: Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through in vitro and in vivo evaluations. METHODS: The 69 compounds were evaluated in vitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99)...
May 2016: Archives of Medical Research
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
Alvaro A Ordonez, Edward A Weinstein, Lauren E Bambarger, Vikram Saini, Yong S Chang, Vincent P DeMarco, Mariah H Klunk, Michael E Urbanowski, Kimberly L Moulton, Allison M Murawski, Supriya Pokkali, Alvin S Kalinda, Sanjay K Jain
: The modern patient is increasingly susceptible to bacterial infections including those due to multi-drug resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. METHODS: We systematic screened 961 random, radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria - Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria...
September 15, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
G K Raju, Karthik Gurumurthi, Reuben Domike
The analysis of benefit and risk is an important aspect of decision-making throughout the drug lifecycle. In this work, the use of a benefit-risk analysis approach to support decision-making was explored. The proposed approach builds on the qualitative FDA approach to include a more explicit analysis based on international standards and guidance that enables aggregation and comparison of benefit and risk on a common basis and a lifecycle focus. The approach is demonstrated on six decisions over the lifecycle (e...
September 14, 2016: Clinical Pharmacology and Therapeutics
Hongbo Shen, Feifei Wang, Gucheng Zeng, Ling Shen, Han Cheng, Dan Huang, Richard Wang, Lijun Rong, Zheng W Chen
While there is an urgent need to develop new and effective drugs for treatment of tuberculosis (TB) and multi-drug resistant TB (MDR-TB), repurposing FDA (U.S. Food and Drug Administration) -approved drugs for development of anti-TB agents may decrease time and effort from bench to bedside. Here, we employed host cell-based high throughput screening (HTS) assay to screen and characterize FDA-approved, off-patent library drugs for anti-Mycobacterium tuberculosis (MTB) activities. The cell-based HTS allowed us to identify an anti-cancer drug of bis-biguanide dihydrochloride (BBD) as potent anti-mycobacteria agent...
2016: Scientific Reports
Susan van den Hof, David Collins, Firdaus Hafidz, Demissew Beyene, Aigul Tursynbayeva, Edine Tiemersma
BACKGROUND: One of the main goals of the post-2015 global tuberculosis (TB) strategy is that no families affected by TB face catastrophic costs. We revised an existing TB patient cost measurement tool to specifically also measure multi-drug resistant (MDR) TB patients' costs and applied it in Ethiopia, Indonesia and Kazakhstan. METHODS: Through structured interviews with TB and MDR-TB patients in different stages of treatment, we collected data on the direct (out of pocket) and indirect (loss of income) costs of patients and their families related to the diagnosis and treatment of TB and MDR-TB...
2016: BMC Infectious Diseases
Shinwon Lee, Sun Hee Lee, Jeong Ha Mok, Su Jin Lee, Kye Hyung Kim, Jeong Eun Lee, Seung Geun Lee, Joo Seop Chung, Ihm Soo Kwak
The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0...
November 2016: Yonsei Medical Journal
Tsedale Semunigus, Belay Tessema, Setegn Eshetie, Feleke Moges
BACKGROUND: Tuberculosis (TB) remains one of the globe's deadliest communicable diseases. The homeless individuals are at high risk to acquire TB and multi-drug resistant TB (MDR-TB), because of their poor living conditions and risky behaviors. Tuberculosis and MDR-TB in the homeless individuals can pose a risk to entire communities. However, the magnitude of the problem is not known in Ethiopia. Therefore, the aim of this study was to determine the prevalence and associated factors of smear positive pulmonary TB (PTB) and MDR-TB among homeless individuals in Dessie and Debre Birhan towns, Northeast Ethiopia...
2016: Annals of Clinical Microbiology and Antimicrobials
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
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