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Jingjing Luo, Xia Yu, Guanglu Jiang, Yuhong Fu, Fengmin Huo, Yifeng Ma, Fen Wang, Yuanyuan Shang, Qian Liang, Yi Xue, Hairong Huang
Due to the natural resistance of non-tuberculous mycobacteria(NTM) to lots of antibiotics,treatment of diseases caused by NTM is often long-termed but less successful.The main goal of this study was to evaluate the in vitro susceptibility to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing,China. Furthermore,47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium(SGM) species.The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well...
May 14, 2018: Antimicrobial Agents and Chemotherapy
Nicole C Ammerman, Rosemary V Swanson, Elaine M Bautista, Deepak V Almeida, Vikram Saini, Till F Omansen, Haidan Guo, Yong Seok Chang, Si-Yang Li, Asa Tapley, Rokeya Tasneen, Sandeep Tyagi, Fabrice Betoudji, Chivonne Moodley, Bongani Ngcobo, Logan Pillay, Linda A Bester, Sanil D Singh, Richard E Chaisson, Eric Nuermberger, Jacques H Grosset
The anti-leprosy drug clofazimine was recently repurposed as part of a newly endorsed short-course regimen for multidrug-resistant tuberculosis. It also enables significant treatment-shortening when added to the first-line regimen for drug-susceptible tuberculosis in a mouse model. However, clofazimine causes dose- and duration-dependent skin discoloration in patients, and the optimal clofazimine dosing strategy in the context of the first-line regimen is unknown. We utilized a well-established mouse model to systematically address the impact of duration, dose, and companion drugs on the treatment-shortening activity of clofazimine in the first-line regimen...
May 7, 2018: Antimicrobial Agents and Chemotherapy
Marcelo Grossi Araújo, Nathalie Silva Cirilo, Soraya Neves Marques Barbosa Dos Santos, Claudemir Roberto Aguilar, Antonio Carlos Martins Guedes
Lobomycosis or lacaziosis is a chronic granulomatous fungal infection caused by Lacazia loboi. Most cases are restricted to tropical regions. Transmission is believed to occur through traumatic inoculation in the skin, mainly in exposed areas. It is characterized by keloid-like nodules. There are only a few hundred cases reported. The differential diagnoses include many skin conditions, and treatment is difficult. The reported case, initially diagnosed as keloid, proved to be refractory to surgical treatment alone...
March 2018: Anais Brasileiros de Dermatologia
Yuanyuan Chen, Jiazhen Chen, Shuo Zhang, Wanliang Shi, Wenhong Zhang, Min Zhu, Ying Zhang
Mycobacterium abscessus ( Mab ) is a major non-tuberculous mycobacterial (NTM) pathogen responsible for about 80% of all pulmonary infections caused by rapidly growing mycobacteria. Clofazimine is an effective drug active against Mab , but the mechanism of resistance to clofazimine in Mab is unknown. To investigate the molecular basis of clofazimine resistance in Mab. We isolated 29 Mab mutants resistant to clofazimine, and subjected them to whole genome sequencing to identify possible mutations associated with clofazimine resistance...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Sandra M W van de Wiel, D Rudi de Waart, Ronald P J Oude Elferink, Stan F J van de Graaf
Background & Aims: The organic solute transporter α-β (OSTα-OSTβ) mainly facilitates transport of bile acids across the basolateral membrane of ileal enterocytes. Therefore, inhibition of OSTα-OSTβ might have similar beneficial metabolic effects as intestine-specific agonists of the major nuclear receptor for bile acids, the farnesoid X receptor (FXR). However, no OSTα-OSTβ inhibitors have yet been identified. Methods: Here, we developed a screen to identify specific inhibitors of OSTα-OSTβ using a genetically encoded Förster Resonance Energy Transfer (FRET)-bile acid sensor that enables rapid visualization of bile acid efflux in living cells...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Mohammad Rehan Ajmal, Fahad Almutairi, Nida Zaidi, Parvez Alam, Mohammad Khursheed Siddiqi, MohsinVahid Khan, Masih Uzzaman, Mohd Ishtikhar, Rizwan Hasan Khan
Alpha1-acid glycoprotein (AAG) is a major acute phase protein of human plasma. Binding of clofazimine to AAG is investigated using optical spectroscopy and molecular docking tools. We found significant quenching of intrinsic fluorescence of AAG upon the binding of clofazimine, binding mode is static with binding constant of 3.52x104 at 298K. The Gibbs free energy change is found to be negative for the interaction of clofazimine with AAG indicating spontaneity of the binding process. Binding of clofazimine induced ordered structure in protein and lead to molecular compaction...
April 19, 2018: Journal of Biomolecular Structure & Dynamics
Lorenzo Angiolini, Sabrina Valetti, Boiko Cohen, Adam Feiler, Abderrazzak Douhal
We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles...
April 18, 2018: Physical Chemistry Chemical Physics: PCCP
A J Garcia-Prats, E M Svensson, E D Weld, H S Schaaf, A C Hesseling
After decades of neglect, data are finally becoming available on the appropriate, safe dosing of key second-line anti-tuberculosis drugs used for treating multidrug-resistant tuberculosis (MDR-TB) in children, including levofloxacin (LVX), moxifloxacin (MFX), linezolid (LZD) and delamanid (DLM). Much needed data on some novel and repurposed drugs are still lacking, including for bedaquiline (BDQ), pretomanid (PTM) and clofazimine (CFZ). We review the status of pharmacokinetic (PK) and safety studies of key anti-tuberculosis medications in children with MDR-TB, identify priority knowledge gaps and note ongoing work to address those gaps, in the context of planning for an efficacy trial in children with MDR-TB...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
Tulshidas S Patil, Ashwini S Deshpande, Shirish Deshpande
Clofazimine (CFZ), a riminophenazine derivative and a crucial drug in the treatment of lepromatous leprosy, has been reintroduced clinically to treat multidrug-resistant tuberculosis. CFZ holds both antimycobacterial and anti-inflammatory properties. But, due to its highly hydrophobic, polar and photosensitive nature, it is challenging to extract and quantify the drug from different biological fluids and its pharmaceutical formulations. This has also hampered the pharmacokinetic evaluation of the CFZ. This article accentuates various analytical methods viz...
April 5, 2018: Critical Reviews in Analytical Chemistry
Amal Hamieh, Ralph Tayyar, Houssam Tabaja, Saeed E L Zein, Pierre Bou Khalil, Nathalie Kara, Zeina A Kanafani, Nadim Kanj, Imad Bou Akl, George Araj, Ghina Berjaoui, Souha S Kanj
OBJECTIVE: The objective of this study is to describe the clinical significance of Mycobacterium simiae at a major tertiary care center in Lebanon. METHODS: This is a retrospective study of patients with positive cultures for M. simiae isolated between 2004 and 2016 at the American University of Beirut Medical Center. RESULTS: This study included 103 M. simiae isolates recovered from 51 patients. Their mean age was 62.7 years. The majority were males and smokers...
2018: PloS One
J L du Preez, M E Aucamp, C Burger, M Gerber, J M Viljoen, L van Zyl, J du Plessis
The aim of this study was to develop and validate a novel HPLC method for the simultaneous analysis of artemisone, clofazimine and decoquinate. Detection was obtained at two wavelengths; 284 nm (clofazimine) and 210 nm (artemisone and decoquinate). Gradient elution was used with mobile phase A (A) consisting of 0.005 M sodium octanesulphonic-acid (pH 3.5) and mobile phase B (B) of HPLC grade acetonitrile. The flow rate was set to 1.0 ml/min with (A) at 35% and (B) at 65% for 2 min, followed by a gradient shift of 10/90% ((A)/(B)) over a duration of 4 min...
March 5, 2018: Die Pharmazie
S Tiberi, M Muñoz-Torrico, R Duarte, M Dalcolmo, L D'Ambrosio, G-B Migliori
Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested...
March 2018: Pulmonology
Jun An, Xuejuan Bai, Mengqiu Gao, Naihui Chu, Hairong Huang, Hongyin Xu, Xiuping Zhang, Baoxia Li, Cailiu Huang, Haixia Cai, Fengqin Zhang, Yu Pang, Liang Li
OBJECTIVE: Our objective was to describe trends in anti-tuberculosis (TB) drug prescribing of inpatients from 2011 to 2015 in a National TB Hospital. METHODS: We carried out this study in March 2016, which retrospectively reviewed the medical records of all inpatients diagnosed as tuberculosis between 2011 and 2015. We recorded the medication used for the treatment of TB during the inpatient period. RESULTS: A total of 11465 inpatients from Beijing Chest Hospital were enrolled in this analysis...
February 21, 2018: Journal of Global Antimicrobial Resistance
Perpétua do Socorro Silva Costa, Lucas Rosa Fraga, Thayne Woycinck Kowalski, Egon Luiz Rodrigues Daxbacher, Lavínia Schuler-Faccini, Fernanda Sales Luiz Vianna
Erythema Nodosum Leprosum (ENL) occurs due to the immunological complication of multibacillary leprosy and is characterized by painful nodules and systemic compromising. It is usually recurrent and/or chronic and has both physical and economic impact on the patient, being a very important cause of disability. In addition, ENL is a major health problem in countries where leprosy is endemic. Therefore, adequate control of this condition is important. The management of ENL aims to control acute inflammation and neuritis and prevent the onset of new episodes...
July 2018: Acta Tropica
Mark H Adelman, Doreen J Addrizzo-Harris
PURPOSE OF REVIEW: To highlight recent original research and specialty society guidelines regarding the diagnosis and treatment of nontuberculous mycobacterial (NTM) pulmonary disease. RECENT FINDINGS: The prevalence of NTM pulmonary disease has risen in recent years. The prevalence of individual NTM species varies geographically, although Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC) remain among the most commonly encountered in many regions...
May 2018: Current Opinion in Pulmonary Medicine
Chao Chen, Susana Gardete, Robert Sander Jansen, Annanya Shetty, Thomas Dick, Kyu Y Rhee, Véronique Dartois
Mycobacterium tuberculosis kills more people than any other bacterial pathogen and is becoming increasingly untreatable due to the emergence of resistance. Verapamil, an FDA-approved calcium channel blocker, potentiates the effect of several antituberculosis (anti-TB) drugs in vitro and in vivo This potentiation is widely attributed to inhibition of the efflux pumps of M. tuberculosis , resulting in intrabacterial drug accumulation. Here, we confirmed and quantified verapamil's synergy with several anti-TB drugs, including bedaquiline (BDQ) and clofazimine (CFZ), but found that the effect is not due to increased intrabacterial drug accumulation...
May 2018: Antimicrobial Agents and Chemotherapy
Sukumaran Pradeep Nair
Background and Aims: Multidrug therapy (MDT) in leprosy has brought the prevalence of leprosy to elimination levels. However, these drugs are not without toxicity. The primary aim of this study was to find the prevalence of adverse drug reactions (ADR) to MDT and the secondary aim to study the clinical features of these drug reactions. Materials and Methods: This is a19-year retrospective descriptive study of all new leprosy cases with ADR to MDT, requiring a change in regime...
January 2018: Indian Dermatology Online Journal
Luíse L Chaves, Sofia Lima, Alexandre C C Vieira, Domingos Ferreira, Bruno Sarmento, Salette Reis
The aim of this work was to develop solid lipid nanoparticles (SLNs) loaded with clofazimine (CLZ) (SLNs-CLZ) to overcome its intrinsic toxicity and low water solubility, for oral drug delivery. A Box-Behnken design was constructed to unravel the relations between the independent variables in the selected responses. The optimized SLNs-CLZ exhibited the following properties: particle size ca 230 nm, zeta potential of -34.28 mV, association efficiency of 72% and drug loading of 2.4%, which are suitable for oral delivery...
February 2018: Journal of the Royal Society, Interface
Qingfeng Wang, Yu Pang, Wei Jing, Yufeng Liu, Na Wang, Hongyun Yin, Qing Zhang, Zhizhong Ye, Min Zhu, Fujian Li, Ping Liu, Tingting Wu, Wei Chen, Wei Wu, Zhihua Qin, Chao Qiu, Qunyi Deng, Tao Xu, Jing Wang, Ru Guo, Yadong Du, Jun Wang, Hairong Huang, Xiaohong Chen, Naihui Chu
We performed a multicenter, prospective, randomized study to investigate the efficacy and safety of clofazimine (CLO) for treatment of extensively drug-resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR-TB were randomly assigned to either the control group or the CLO group, both of which received 36 months of individually customized treatment. The primary endpoint was the time to sputum culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion...
April 2018: Antimicrobial Agents and Chemotherapy
Matthew Schwartz, Stefanie Fisher, Elizabeth Story-Roller, Gyanu Lamichhane, Nicole Parrish
Patients with cystic fibrosis (CF) are at risk for recurrent pulmonary infections due to increased viscosity of airway secretions, leading to persistent colonization with pathogenic bacteria, including nontuberculous mycobacteria (NTM). Extensive antibiotic use for treatment of infections has led to increasing antimicrobial resistance, which is a significant barrier to the treatment of NTMs. We examined the in vitro activity of several antibiotics against a selection of the most drug-resistant clinical isolates of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium avium complex recovered from CF patients at our institution, as well as paired combinations of antibiotics against a subset of M...
January 25, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
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