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Clofazimine

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https://www.readbyqxmd.com/read/28438129/severe-type-1-upgrading-leprosy-reaction-in-a-renal-transplant-recipient-a-paradoxical-manifestation-associated-with-deficiency-of-antigen-specific-regulatory-t-cells
#1
Ana Paula Vieira, Maria Angela Bianconcini Trindade, Flávio Jota de Paula, Neusa Yurico Sakai-Valente, Alberto José da Silva Duarte, Francine Brambate Carvalhinho Lemos, Gil Benard
BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient...
April 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28392809/in-vitro-susceptibility-of-mycobacterium-ulcerans-isolates-to-selected-antimicrobials
#2
Enid Owusu, Mercy J Newman, Kwesi K Addo, Phyllis Addo
Background. The current definitive treatment of Buruli ulcer with antibiotics makes the issue of antimicrobial drug resistance an unavoidable one. This is as a result of drug misuse by health personnel and patients' noncompliance to treatment regimen. Monitoring of these factors and screening for new effective antimicrobials are crucial to effective management of Buruli ulcer disease. This study therefore investigated the inhibitory activity of some antibiotics against isolates of Mycobacterium ulcerans. Methods...
2017: Canadian Journal of Infectious Diseases & Medical Microbiology
https://www.readbyqxmd.com/read/28361737/therapy-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis
#3
Barbara J Seaworth, David E Griffith
The global epidemic of multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. Extensively drug-resistant tuberculosis (XDR-TB), MDR-TB with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of MDR cases globally. Cases in India, China, and the Russian Federation account for >45% of the cases of MDR-TB...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28348153/a-clofazimine-containing-regimen-for-the-treatment-of-mycobacterium-abscessus-lung-disease
#4
Bumhee Yang, Byung Woo Jhun, Seong Mi Moon, Hyun Lee, Hye Yun Park, Kyeongman Jeon, Dae Hun Kim, Su-Young Kim, Sung Jae Shin, Charles L Daley, Won-Jung Koh
Patients with lung disease caused by Mycobacterium abscessus subspecies abscessus (hereafter M. abscessus) typically have poor treatment outcomes. Although clofazimine (CFZ) has been increasingly used in the treatment of M. abscessus lung disease in clinical practice, there are no published data on its effectiveness for this disease. This study sought to evaluate the clinical efficacy of a CFZ-containing regimen for the treatment of M. abscessus lung disease. We performed a retrospective review of the medical records of 42 patients with M...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28338408/clofazimine-encapsulation-in-nanoporous-silica-particles-for-the-oral-treatment-of-antibiotic-resistant-mycobacterium-tuberculosis-infections
#5
Sabrina Valetti, Xin Xia, Joana Costa-Gouveia, Priscille Brodin, Marie-Françoise Bernet-Camard, Margareta Andersson, Adam Feiler
AIM: First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections. MATERIALS & METHODS: Solid-state characterization of several CLZ-encapsulated NSP formulations was followed by in vitro drug solubility, Caco-2 intestinal cells drug permeability and TB antibacterial activity. RESULTS: NSPs stabilize the amorphous state of CLZ (shelf stability >6 months) and dramatically increase the drug solubility in simulated gastric fluid (up to 20-fold) with different dissolution kinetics depending on the NSPs used...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28333192/susceptibilities-of-mdr-mycobacterium-tuberculosis-isolates-to-unconventional-drugs-compared-with-their-reported-pharmacokinetic-pharmacodynamic-parameters
#6
Joseph S Cavanaugh, Ruwen Jou, Mei-Hua Wu, Tracy Dalton, Ekaterina Kurbatova, Julia Ershova, J Peter Cegielski
Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment...
February 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28331044/effectiveness-and-safety-of-clofazimine-in%C3%A2-multidrug-resistant-tuberculosis-a%C3%A2-nationwide-report-from-brazil
#7
Margareth Dalcolmo, Regina Gayoso, Giovanni Sotgiu, Lia D'Ambrosio, Jorge L Rocha, Liamar Borga, Fatima Fandinho, Jose U Braga, Vera M N Galesi, Draurio Barreira, Denise A Sanchez, Fernanda Dockhorn, Rosella Centis, Jose A Caminero, Giovanni B Migliori
Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day(-1) (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28320727/primary-clofazimine-and-bedaquiline-resistance-among-isolates-from-patients-with-multidrug-resistant-tuberculosis
#8
Jian Xu, Bin Wang, Minghao Hu, Fengmin Huo, Shaochen Guo, Wei Jing, Eric Nuermberger, Yu Lu
Clofazimine has been repurposed for the treatment of tuberculosis especially for MDR-TB. To test the susceptibility to clofazimine for Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate Alamar blue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. Five clofazimine-resistant strains isolated from previously treated pre-XDR and XDR-TB patients without prior exposure to clofazimine or bedaquiline had clofazimine MICs ≥1...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28303962/identification-of-novel-chemotherapeutic-strategies-for-metastatic-uveal-melanoma
#9
Paolo Fagone, Rosario Caltabiano, Andrea Russo, Gabriella Lupo, Carmelina Daniela Anfuso, Maria Sofia Basile, Antonio Longo, Ferdinando Nicoletti, Rocco De Pasquale, Massimo Libra, Michele Reibaldi
Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295815/elucidating-the-interaction-of-clofazimine-with-bovine-liver-catalase-a-comprehensive-spectroscopic-and-molecular-docking-approach
#10
Masihuz Zaman, Saima Nusrat, Syed Mohammad Zakariya, Mohsin Vahid Khan, Mohammad Rehan Ajmal, Rizwan Hasan Khan
Nowadays, understanding of interface between protein and drugs has become an active research area of interest. These types of interactions provide structural guidelines in drug design with greater clinical efficacy. Thus, structural changes in catalase induced by clofazimine were monitored by various biophysical techniques including UV-visible spectrometer, fluorescence spectroscopy, circular dichroism, and dynamic light scattering techniques. Increase in absorption spectra (UV-visible spectrum) confers the complex formation between drug and protein...
March 14, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28270989/detecting-ordered-small-molecule-drug-aggregates-in-live-macrophages-a-multi-parameter-microscope-image-data-acquisition-and-analysis-strategy
#11
Phillip Rzeczycki, Gi Sang Yoon, Rahul K Keswani, Sudha Sud, Kathleen A Stringer, Gus R Rosania
Following prolonged administration, certain orally bioavailable but poorly soluble small molecule drugs are prone to precipitate out and form crystal-like drug inclusions (CLDIs) within the cells of living organisms. In this research, we present a quantitative multi-parameter imaging platform for measuring the fluorescence and polarization diattenuation signals of cells harboring intracellular CLDIs. To validate the imaging system, the FDA-approved drug clofazimine (CFZ) was used as a model compound. Our results demonstrated that a quantitative multi-parameter microscopy image analysis platform can be used to study drug sequestering macrophages, and to detect the formation of ordered molecular aggregates formed by poorly soluble small molecule drugs in animals...
February 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28256460/international-open-trial-of-uniform-multidrug-therapy-regimen-for-leprosy-patients-findings-implications-for-national-leprosy-programmes
#12
Ponnaiah Manickam, Sanjay M Mehendale, Bathyala Nagaraju, Kiran Katoch, Abdul Jamesh, Ramalingam Kutaiyan, Shen Jianping, Shivakumar Mugudalabetta, Vitthal Jadhav, Prabu Rajkumar, Jayasree Padma, Kanagasabai Kaliaperumal, Vijayakumar Pannikar, Padabettu Krishnamurthy, Mohan D Gupte
BACKGROUND & OBJECTIVES: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. METHODS: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P...
October 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28256383/the-challenge-of-the-new-tuberculosis-drugs
#13
REVIEW
Simon Tiberi, Ruaridh Buchanan, José A Caminero, Rosella Centis, Marcos Abdo Arbex, Miguel Salazar, Jessica Potter, Giovanni Battista Migliori
Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation...
March 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28240574/elucidating-the-role-of-clofazimine-for-the-treatment-of-tuberculosis
#14
M R O'Donnell, N Padayatchi, J Z Metcalfe
Clofazimine (CFZ), a riminophenazine and a key component of the treatment regimen for lepromatous leprosy, has been rehabilitated clinically for the treatment of multidrug-resistant tuberculosis (MDR-TB). Observational studies and a randomized control trial suggest efficacy in the treatment of MDR-TB and the potential for treatment shortening. Animal and translational research have shown mixed results. In this article, we review key clinical, animal, and translational data to better understand the potential role of CFZ in the treatment of MDR-TB and in shortening anti-tuberculosis treatment...
December 1, 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28240568/-re-moving-the-needle-prospects-for-all-oral-treatment-for-multidrug-resistant-tuberculosis
#15
M Milstein, A Brzezinski, F Varaine, C D Mitnick
BACKGROUND: Currently recommended regimens for multidrug-resistant tuberculosis (MDR-TB) contain painful daily injections and are unsuccessful in approximately half of patients. Removal of the injectable agent to fashion all-oral regimens could transform MDR-TB treatment and access to care. OBJECTIVE: To explore evidence for all-oral treatment regimens. DESIGN: We review evidence on drugs that could be included in injection-free MDR-TB regimens...
December 1, 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28199712/clofazimine-mechanisms-of-action-in-mycobacteria-hiv-and-cancer
#16
William Levis
No abstract text is available yet for this article.
February 12, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28158186/a-high-throughput-phenotypic-screen-identifies-clofazimine-as-a-potential-treatment-for-cryptosporidiosis
#17
Melissa S Love, Federico C Beasley, Rajiv S Jumani, Timothy M Wright, Arnab K Chatterjee, Christopher D Huston, Peter G Schultz, Case W McNamara
Cryptosporidiosis has emerged as a leading cause of non-viral diarrhea in children under five years of age in the developing world, yet the current standard of care to treat Cryptosporidium infections, nitazoxanide, demonstrates limited and immune-dependent efficacy. Given the lack of treatments with universal efficacy, drug discovery efforts against cryptosporidiosis are necessary to find therapeutics more efficacious than the standard of care. To date, cryptosporidiosis drug discovery efforts have been limited to a few targeted mechanisms in the parasite and whole cell phenotypic screens against small, focused collections of compounds...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28131606/antimicrobial-susceptibility-and-mic-distribution-of-41-drugs-against-clinical-isolates-from-china-and-reference-strains-of-nontuberculous-mycobacteria
#18
Guilian Li, Hui Pang, Qian Guo, Mingxiang Huang, Yanhong Tan, Chao Li, Jianhao Wei, Yuanzhi Xia, Yi Jiang, Xiuqin Zhao, Haican Liu, Li-Li Zhao, Zhiguang Liu, Donglei Xu, Kanglin Wan
To treat nontuberculous mycobacteria (NTM) infections more optimally, further research pertaining to mycobacterial susceptibility to antimicrobial agents is required. A total of 82 species of NTM reference strains and 23 species of NTM clinical isolates were included. Minimum inhibitory concentrations (MICs) for 41 drugs were determined using the microdilution method in cation-adjusted Mueller-Hinton broth. The results showed that most of the NTM were susceptible to aminoglycosides, quinolones, three macrolides (clarithromycin, azithromycin and roxithromycin), cefmetazole, linezolid and capreomycin...
March 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28122281/anti-cancer-effect-of-clofazimine-as-a-single-agent-and-in-combination-with-cisplatin-on-u266-multiple-myeloma-cell-line
#19
İpek Z Durusu, Hazal H Hüsnügil, Heval Ataş, Ayşenur Biber, Selin Gerekçi, Ezgi A Güleç, Can Özen
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28115355/synergistic-interactions-of-mmpl3-inhibitors-with-antitubercular-compounds-in-vitro
#20
Wei Li, Andrea Sanchez-Hidalgo, Victoria Jones, Vinicius Calado Nogueira de Moura, E Jeffrey North, Mary Jackson
A number of inhibitors of the essential Mycobacterium tuberculosis mycolic acid transporter, MmpL3, are currently under development as potential novel antituberculosis agents. Using the checkerboard method to study the interaction profiles of various antituberculosis drugs or experimental compounds with two different chemotypes inhibiting this transporter (indolcarboxamides and adamantyl ureas), we showed that MmpL3 inhibitors act synergistically with rifampin, bedaquiline, clofazimine, and β-lactams.
April 2017: Antimicrobial Agents and Chemotherapy
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