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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, A Zumla, G-B Migliori
Tuberculosis (TB) continues to cause more deaths worldwide than any other infectious disease. Even though global TB incidence has been decreasing for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity, mortality, and cost. Since the advent of rifampicin in the 1960s, and the implementation of the standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have changed the first line regimen. This regimen while effective, has a long duration and pill burden, which has received little investment and innovation...
February 24, 2018: Revista Portuguesa de Pneumologia
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...
February 20, 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...
February 20, 2018: Current Opinion in Pulmonary Medicine
Chao Chen, Susana Gardete, Robert Sander Jansen, Annanya Shetty, Thomas Dick, Kyu Y Rhee, Véronique Dartois
Mycobacterium tuberculosis (Mtb) 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 anti-tuberculosis (TB) drugs in vitro and in vivo. This potentiation is widely attributed to inhibition of Mtb's efflux pumps, resulting in intrabacterial drug accumulation. Here, we confirm and quantify verapamil's synergy with several anti-TB drugs, including bedaquiline and clofazimine, but find that this effect is not due to increased intrabacterial drug accumulation...
February 20, 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 and 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 end-point was the time to sputum-culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion...
January 29, 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
Leah Lande, Jason George, Theodore Plush
PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related pulmonary disease has been increasing because of environmental factors, changes in organism virulence, and evolving host susceptibility. Treatment is often complicated by adverse effects, development of drug resistance, and refractory disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization of water, soil, or dusts are the likely sources of MAC-related pulmonary disease in susceptible individuals...
April 2018: Current Opinion in Infectious Diseases
R S Jumani, K Bessoff, M S Love, P Miller, E E Stebbins, J E Teixeira, M A Campbell, M J Meyers, J A Zambriski, V Nunez, A K Woods, C W McNamara, C D Huston
Cryptosporidiosis causes life-threatening diarrhea in children under age five, and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to a need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization...
January 16, 2018: Antimicrobial Agents and Chemotherapy
Nazir A Ismail, Shaheed V Omar, Lavania Joseph, Netricia Govender, Linsay Blows, Farzana Ismail, Hendrik Koornhof, Andries W Dreyer, Koné Kaniga, Norbert Ndjeka
BACKGROUND: Bedaquiline (BDQ) is a novel agent approved for use in combination treatment of multi-drug resistant tuberculosis (MDR-TB). We sought to determine BDQ epidemiological cut-off values (ECVs), define and assess interpretive criteria against putative resistance associated variants (RAVs), microbiological outcomes and cross resistance with clofazimine (CFZ). METHODS: A retrospective cohort study was conducted. Minimal inhibitory concentrations (MIC) to BDQ were determined using 7H9 broth microdilution (BMD) and MGIT960...
January 9, 2018: EBioMedicine
Jinsheng Lin, Zhenghuai Lin, Dan Li, Mengxue Feng, Qin Yang, Wenping Hu, Yang Han, Wenquan Zhu, Min Li, LuShan Yu
Analytical solutions of clofazimine drug substance stored in glass HPLC vials were found to undergo degradation at room temperature occasionally. At the time of each sample preparation, it was unpredictable if a particular solution would undergo such solution degradation. Once the degradation peak was observed in a particular vial, typically within 24h, it would keep growing until reaching a total yield of approximately 2%. By using a strategy that combines LC-PDA/UV-MSn with mechanism-based stress studies, followed by preparative HPLC separation and subsequent structure characterization by 1D and 2D NMR, the unknown peak was identified as a clofazimine nitrite ester...
November 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
Matteo Romio, Giulia Morgese, Lucca Trachsel, Samuel Babity, Cristina Paradisi, Davide Brambilla, Edmondo M Benetti
Functional block copolymers based on poly(2-oxazoline)s are versatile building blocks for the fabrication of dual-drug delivery nanoparticles (NPs) for anticancer chemotherapy. Core-shell NPs are fabricated from diblock copolymers featuring a long and hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) block coupled to a relatively short and functionalizable poly(2-methylsuccinate-2-oxazoline) (PMestOXA) segment. The PMOXA block stabilizes the NP dispersions, whereas the PMestOXA segment is used to conjugate pterostilbene, a natural bioactive phenolic compound that is used as lipophilic model-drug and constitutes the hydrophobic core of the designed NPs...
January 8, 2018: Biomacromolecules
A Trébucq, V Schwoebel, Z Kashongwe, A Bakayoko, C Kuaban, J Noeske, S Hassane, B Souleymane, A Piubello, F Ciza, V Fikouma, M Gasana, M Ouedraogo, M Gninafon, A Van Deun, D M Cirillo, K G Koura, H L Rieder
SETTING: Nine countries in West and Central Africa. OBJECTIVE: To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs. DESIGN: Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
G Maartens, M J E Brill, M Pandie, E M Svensson
BACKGROUND: Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ. METHODS: We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
Thi Van Anh Nguyen, Richard M Anthony, Anne-Laure Bañuls, Dinh Hoa Vu, Jan-Willem C Alffenaar
Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance...
November 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Luíse L Chaves, Sofia A Costa Lima, Alexandre C C Vieira, Luísa Barreiros, Marcela A Segundo, Domingos Ferreira, Bruno Sarmento, Salette Reis
The use of polymeric nanoparticles as delivery systems is a promising tool to overcome drawbacks related to low aqueous solubility of drugs, which limit their in vivo bioavailability. The aim of this study was to decrease clofazimine (CLZ) toxicity using experimental design to formulate CLZ loaded in PLGA nanoparticles (NPs-CLZ) through a Plackett-Burman design (PBD). A screening PBD was constructed with twelve formulations involving six variables among process and formulation parameters and the selected responses were particle size, polydispersity index (PDI), association efficiency (AE) and drug loading (DL)...
January 15, 2018: European Journal of Pharmaceutical Sciences
Wing Wai Yew, Dachao Liang, Denise P Chan, Wanliang Shi, Ying Zhang
No abstract text is available yet for this article.
October 1, 2017: Journal of Antimicrobial Chemotherapy
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