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Clofazimine

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https://www.readbyqxmd.com/read/28930155/identification-of-agents-active-against-methicillin-resistant-staphylococcus-aureus-usa300-from-a-clinical-compound-library
#1
Hongxia Niu, Rebecca Yee, Peng Cui, Lili Tian, Shuo Zhang, Wanliang Shi, David Sullivan, Bingdong Zhu, Wenhong Zhang, Ying Zhang
Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat for effective treatment of several difficult-to-treat infections in humans. To identify potential new treatment options for MRSA infections, we screened a clinical compound library consisting of 1524 compounds using a growth inhibition assay in 96-well plates. We identified 34 agents which are either bacteriostatic or bactericidal against log-phase clinical MRSA strain USA300. Among them, 9 candidates (thonzonium, cetylpyridinium, trilocarban, benzododecinium, bithionol, brilliant green, chlorquinaldol, methylbenzethonium and green violet) are known antiseptics, 11 candidates are known antibiotics currently recommended for the treatment of MRSA...
September 20, 2017: Pathogens
https://www.readbyqxmd.com/read/28929769/design-and-solidification-of-fast-releasing-clofazimine-nanoparticles-for-treatment-of-cryptosporidiosis
#2
Yingyue Zhang, Jie Feng, Simon A McManus, Hoang D Lu, Kurt D Ristroph, Eugene J Cho, Ellen L Dobrijevic, Hak-Kim Chan, Robert K Prud'homme
Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable...
September 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28880343/granuloma-faciale-treatment-a-systematic-review
#3
Claudia Lindhaus, Peter Elsner
Granuloma faciale is an uncommon benign chronic dermatosis characterized by reddish-brown to violaceous asymptomatic plaques appearing predominantly on the face. The pathogenesis of granuloma faciale remains unclear, and it is frequently unresponsive to therapy. This systematic review aims to summarize all recent publications on the management of granuloma faciale. The publications are mainly individual case reports, small case series and a few retrospective studies. Treatment options included topical, intralesional and systemic corticosteroids, topical pimecrolimus and tacrolimus, topical and systemic dapsone, systemic hydroxychloroquine, clofazimine, and tumour necrosis factor-alpha inhibitors...
September 7, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28869943/targeting-the-potassium-channel-kv1-3-kills-glioblastoma-cells
#4
Elisa Venturini, Luigi Leanza, Michele Azzolini, Stephanie Kadow, Andrea Mattarei, Michael Weller, Ghazaleh Tabatabai, Michael J Edwards, Mario Zoratti, Cristina Paradisi, Ildikò Szabò, Erich Gulbins, Katrin Anne Becker
BACKGROUND/AIMS: Glioblastoma (GBM) is one of the most aggressive cancers, counting for a high number of the newly diagnosed patients with central nervous system (CNS) cancers in the United States and Europe. Major features of GBM include aggressive and invasive growth as well as a high resistance to treatment. Kv1.3, a potassium channel of the shaker family, is expressed in the inner mitochondrial membrane of many cancer cells. Inhibition of mitochondrial Kv1.3 was shown to induce apoptosis in several tumor cells at doses that were not lethal for normal cells...
September 1, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/28843822/clofazimine-protects-against-mycobacterium-tuberculosis-dissemination-in-the-cns-following-an-aerosol-challenge-in-a-murine-model
#5
Sooraj Baijnath, Chivonne Moodley, Bongani Ngcobo, Sanil D Singh, Hendrik G Kruger, Per I Arvidsson, Tricia Naicker, Alexander Pym, Thavendran Govender
BACKGROUND: Tuberculosis (TB) has been the scourge of the human race for many decades, claiming countless number of lives along the way. This is further complicated by the ability of Mycobacterium tuberculosis (M.tb) to infect extra-pulmonary sites, more specifically the brain. These forms of TB are difficult to treat due to the problems associated with drug delivery across the blood brain barrier (BBB). Linezolid (LZD and clofazimine (CFZ) are two of the more promising anti-TB antibiotics in recent times...
August 23, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28833263/quantitative-analysis-of-clofazimine-lamprene%C3%A2-an-antileprosy-agent-in-human-dried-blood-spots-using-liquid-chromatography-tandem-mass-spectrometry
#6
Wenkui Li, John Doherty, Yunlin Fu, Jimmy Flarakos
An LC-MS/MS method was developed and validated for bioanalysis of clofazimine in human DBS samples in support of a clinical study on multidrug-resistant tuberculosis in developing countries. The validated assay dynamic range was from 10.0 to 2000 ng/mL using a 1/8″ DBS punch. The accuracy and precision of the assay were ±11.0 % (bias) and ≤13.5% (CV) for the LLOQs (10.0 ng/mL) and ± 15% (bias) and ≤ 15% (CV) for all other QC levels. The assay was proved to be free from the possible impact due to spot size and storage temperature (e...
August 19, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28826448/clinical-significance-of-qt-prolonging-drug-use-in-patients-with-mdr-tb-or-ntm-disease
#7
H-Y Yoon, K-W Jo, G B Nam, T S Shim
SETTING: Many drugs with potential QT prolongation effects (QT drugs) have already been used for decades in patients with multidrug-resistant TB (MDR-TB) or non-tuberculous mycobacterial (NTM) disease, but without a common consensus. OBJECTIVE: To investigate the effects of QT drugs on cardiac events in patients with MDR-TB or NTM disease. METHODS: We retrospectively reviewed 373 patients (mean age: 56.4 years) with MDR-TB or NTM disease treated for >1 month with clofazimine (CFZ), moxifloxacin (MFX), bedaquiline (BDQ), delamanid (DLM) or macrolides (clarithromycin or azithromycin)...
September 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28819600/extensively-drug-resistant-tuberculosis-of-the-lumbar-spine-in-a-six-year-old-child-a-case-report
#8
Siddharth Sanjay Shah, Aakanksha Arvind Goregaonkar, Arvind Balkrishna Goregaonkar
INTRODUCTION: The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a challenging paradigm shift faced by the TB control programs worldwide today. The treatment is further compounded with unique management difficulties faced in pediatric patients. Treatment of XDR-TB requires prolonged chemotherapy with second-line drugs which offer lesser potency and increased risk of drug-related side effects. We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT)...
March 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28781126/targeting-mycobacterium-tuberculosis-sensitivity-to-thiol-stress-at-acidic-ph-kills-the-bacterium-and-potentiates-antibiotics
#9
Garry B Coulson, Benjamin K Johnson, Huiqing Zheng, Christopher J Colvin, Robert J Fillinger, Elizabeth R Haiderer, Neal D Hammer, Robert B Abramovitch
Mycobacterium tuberculosis (Mtb) must sense and adapt to immune pressures such as acidic pH during pathogenesis. The goal of this study was to isolate compounds that inhibit acidic pH resistance, thus defining virulence pathways that are vulnerable to chemotherapy. Here, we report that the compound AC2P36 selectively kills Mtb at acidic pH and potentiates the bactericidal activity of isoniazid, clofazimine, and diamide. We show that AC2P36 activity is associated with thiol stress and causes an enhanced accumulation of intracellular reactive oxygen species at acidic pH...
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28776518/fighting-tuberculosis-by-drugs-targeting-nonreplicating-mycobacterium-tuberculosis-bacilli
#10
REVIEW
Angelo Iacobino, Giovanni Piccaro, Federico Giannoni, Alessandro Mustazzolu, Lanfranco Fattorini
Current tuberculosis (TB) treatment requires 6 months of combination therapy with isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol for active TB and 9 months of INH or 3 months of rifapentine (RFP) + INH for latent TB. The lungs of patients with active and latent TB contain heterogeneous mixtures of cellular and caseous granulomas harboring Mycobacterium tuberculosis bacilli ranging from actively replicating (AR) to nonreplicating (NR), phenotypically drug-resistant stages. Several in vitro models to obtain NR cells were reported, including exposure to hypoxia, nutrient starvation, acid + nitric oxide, and stationary phase...
July 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28763601/leprosy-an-overview-of-clinical-features-diagnosis-and-treatment
#11
Marcellus Fischer
Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms...
August 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28751411/effectiveness-and-safety-of-standardised-shorter-regimens-for-multidrug-resistant-tuberculosis-individual-patient-data-and-aggregate-data-meta-analyses
#12
Faiz Ahmad Khan, M A Hamid Salim, Philipp du Cros, Esther C Casas, Atajan Khamraev, Welile Sikhondze, Andrea Benedetti, Mayara Bastos, Zhiyi Lan, Ernesto Jaramillo, Dennis Falzon, Dick Menzies
We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28748609/effectiveness-of-surgical-treatment-of-severe-macrocheilia-in-a-patient-with-orofacial-granulomatosis
#13
C Vassallo, N Rivetti, M Merlino, G Borroni, V Brazzelli
Orofacial granulomatosis (OFG) is the term given to a group of diseases characterized by the presence of non-necrotizing granulomatous inflammation affecting the soft tissues of the orofacial region. Treatment of OFG is often challenging and unsatisfactory. We report on a 32-year-old man with a 2-year history of oedema and swelling of the upper lip without systemic symptoms. The history, clinical features and histopathological findings led to the diagnosis of cheilitis granulomatosa (CG), a disease included in the spectrum of OFG...
July 27, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28739779/in-vitro-drug-susceptibility-of-bedaquiline-delamanid-linezolid-clofazimine-moxifloxacin-and-gatifloxacin-against-extensively-drug-resistant-tuberculosis-from-beijing-china
#14
Yu Pang, Zhaojing Zong, Fengmin Huo, Wei Jing, Yifeng Ma, Lingling Dong, Yunxu Li, Liping Zhao, Yuhong Fu, Hairong Huang
Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore in vitro drug susceptibility of bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MXF), and gatifloxacin (GAT) against 90 XDR-TB strains isolated from patients in China. We also described the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD and BDQ was found in 82 (91...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28719256/therapeutic-dilemma-of-refractory-erythema-nodosum-leprosum
#15
Jianyu Zhu, Degang Yang, Chao Shi, Zhichun Jing
AbstractErythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28711677/extended-spectrum-of-antibiotic-susceptibility-for-tuberculosis-djibouti
#16
Fériel Bouzid, Hélène Astier, Djaltou Aboubaker Osman, Emilie Javelle, Mohamed Osman Hassan, Fabrice Simon, Eric Garnotel, Michel Drancourt
The Horn of Africa suffers from a high prevalence of tuberculosis which is reported to be partly driven by multi-drug resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti; along with their in vitro susceptibility to standard anti-tuberculous antibiotics, in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M...
July 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28705770/in%C3%A2-vitro-activity-of-aminoglycosides-clofazimine-d-cycloserine-and-dapsone-against-83-mycobacterium-avium-complex-clinical-isolates
#17
Chen-Cheng Huang, Ming-Feng Wu, Hui-Chen Chen, Wei-Chang Huang
BACKGROUND/PURPOSE: Treatment success rates for Mycobacterium avium complex (MAC) diseases range from 50% to 55% only. To explore effective antimicrobials against either Mycobacteriumintracellulare or M. avium, we determined in vitro activities of five aminoglycosides, clofazimine, dapsone and d-cycloserine compared with primary (clarithromycin) and secondary (moxifloxacin and linezolid) antimycobacterial agents. METHODS: 83 non-duplicate clinical MAC isolates were collected from sputum and identified at the species level by PCR and restriction enzyme analysis of the 65 kDa hsp and rpoB genes...
June 28, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28704363/uniform-multidrug-therapy-for-leprosy-patients-in-brazil-u-mdt-ct-br-results-of-an-open-label-randomized-and-controlled-clinical-trial-among-multibacillary-patients
#18
RANDOMIZED CONTROLLED TRIAL
Gerson Oliveira Penna, Samira Bührer-Sékula, Lígia Regina Sansigolo Kerr, Mariane Martins de Araújo Stefani, Laura Cunha Rodrigues, Marcelo Grossi de Araújo, Andrea Machado Coelho Ramos, Ana Regina Coelho de Andrade, Maurício Barcelos Costa, Patricia Sammarco Rosa, Heitor de Sá Gonçalves, Rossilene Cruz, Maurício Lima Barreto, Maria Araci de Andrade Pontes, Maria Lúcia Fernandes Penna
BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months)...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28693853/multidrug-therapy-for-leprosy-a-game-changer-on-the-path-to-elimination
#19
REVIEW
Cairns S Smith, Ann Aerts, Paul Saunderson, Joseph Kawuma, Etsuko Kita, Marcos Virmond
Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance...
September 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28554545/cyclodextrin-mesoporous-silica-particle-composites-for-controlled-antibiotic-release-a-proof-of-concept-toward-colon-targeting
#20
Louise Stjern, Sandra Voittonen, Rahel Weldemichel, Sofia Thuresson, Marco Agnes, Gabor Benkovics, Éva Fenyvesi, Milo Malanga, Konstantina Yannakopoulou, Adam Feiler, Sabrina Valetti
Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSP to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine...
May 26, 2017: International Journal of Pharmaceutics
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