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https://www.readbyqxmd.com/read/28209466/pharmacokinetics-and-safety-of-cavosonstat-n91115-in-healthy-and-cystic-fibrosis-adults-homozygous-for-f508del-cftr
#1
Scott H Donaldson, George M Solomon, Pamela L Zeitlin, Patrick A Flume, Alicia Casey, Karen McCoy, Edith T Zemanick, Arun Mandagere, Janice M Troha, Steven A Shoemaker, James F Chmiel, Jennifer L Taylor-Cousar
BACKGROUND: Cavosonstat (N91115), an orally bioavailable inhibitor of S-nitrosoglutathione reductase, promotes cystic fibrosis transmembrane conductance regulator (CFTR) maturation and plasma membrane stability, with a mechanism of action complementary to CFTR correctors and potentiators. METHODS: A Phase I program evaluated pharmacokinetics, drug-drug interactions and safety of cavosonstat in healthy and cystic fibrosis (CF) subjects homozygous for F508del-CFTR...
February 13, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28202091/isolation-unit-for-multidrug-resistant-tuberculosis-patients-in-a-low-endemic-country-a-step-towards-the-world-health-organization-end-tb-strategy
#2
M C Payen, J P VAN Vooren, O Vandenberg, N Clumeck, S DE Wit
Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates...
February 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28196958/transcription-profiling-of-bacillus-subtilis-cells-infected-with-ar9-a-giant-phage-encoding-two-multisubunit-rna-polymerases
#3
Daria Lavysh, Maria Sokolova, Marina Slashcheva, Konrad U Förstner, Konstantin Severinov
Bacteriophage AR9 is a recently sequenced jumbo phage that encodes two multisubunit RNA polymerases. Here we investigated the AR9 transcription strategy and the effect of AR9 infection on the transcription of its host, Bacillus subtilis Analysis of whole-genome transcription revealed early, late, and continuously expressed AR9 genes. Alignment of sequences upstream of the 5' ends of AR9 transcripts revealed consensus sequences that define early and late phage promoters. Continuously expressed AR9 genes have both early and late promoters in front of them...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196957/a-novel-small-molecule-inhibitor-of-the-mycobacterium-tuberculosis-demethylmenaquinone-methyltransferase-meng-is-bactericidal-to-both-growing-and-nutritionally-deprived-persister-cells
#4
Paridhi Sukheja, Pradeep Kumar, Nisha Mittal, Shao-Gang Li, Eric Singleton, Riccardo Russo, Alexander L Perryman, Riju Shrestha, Divya Awasthi, Seema Husain, Patricia Soteropoulos, Roman Brukh, Nancy Connell, Joel S Freundlich, David Alland
Active tuberculosis (TB) and latent Mycobacterium tuberculosis infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating M. tuberculosis "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent M. tuberculosis and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196479/treatment-completion-for-latent-tuberculosis-infection-a-retrospective-cohort-study-comparing-9%C3%A2-months-of-isoniazid-4%C3%A2-months-of-rifampin-and-3%C3%A2-months-of-isoniazid-and-rifapentine
#5
Adelaide H McClintock, McKenna Eastment, Christy M McKinney, Caroline L Pitney, Masahiro Narita, David R Park, Shireesha Dhanireddy, Alexandra Molnar
BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) recommended a new regimen for treatment of latent tuberculosis (three months of weekly isoniazid and rifapentine) in late 2011. While completion rates of this regimen were reported to be higher than nine months of isoniazid, little is known about the completion rates of three months of isoniazid and rifapentine compared to nine months of isoniazid or four months of rifampin in actual use scenarios. METHODS: We conducted a retrospective cohort study comparing treatment completion for latent tuberculosis (TB) infection in patients treated with nine months of isoniazid, three months of isoniazid and rifapentine or four months of rifampin in outpatient clinics and a public health TB clinic in Seattle, Washington...
February 14, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28196219/the-role-of-rifampin-in-leprosy-leprosy-through-a-new-lens
#6
Herbert B Allen, Samuel L Moschella
No abstract text is available yet for this article.
February 8, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28185617/mycobacterium-kansasii
#7
James C Johnston, Leslie Chiang, Kevin Elwood
The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. In contrast to other common nontuberculous mycobacteria, M. kansasii is infrequently isolated from natural water sources or soil. The major reservoir appears to be tap water. Infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. Human-to-human transmission is thought not to occur...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28184344/a-case-of-acute-tubulointerstitial-nephritis-associated-with-rifampin-therapy-presenting-as-fanconi-like-syndrome
#8
Jun Tae Park, Sik Lee, Won Kim, Sung Kwang Park, Kyung Pyo Kang
No abstract text is available yet for this article.
January 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28184157/silver-loaded-nanotubular-structures-enhanced-bactericidal-efficiency-of-antibiotics-with-synergistic-effect-in-vitro-and-in-vivo
#9
Na Xu, Hao Cheng, Jiangwen Xu, Feng Li, Biao Gao, Zi Li, Chenghao Gao, Kaifu Huo, Jijiang Fu, Wei Xiong
Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag) nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28181840/transdermal-delivery-of-isoniazid-and-rifampin-in-guinea-pigs-by-electro-phonophoresis
#10
Suting Chen, Yi Han, Daping Yu, Fengmin Huo, Fen Wang, Yunxu Li, Lingling Dong, Zhidong Liu, Hairong Huang
Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28177134/the-influence-of-combination-use-of-cyp450-inducers-on-the-pharmacokinetics-of-voriconazole-a-systematic-review
#11
REVIEW
T-Y Li, W Liu, K Chen, S-Y Liang, F Liu
WHAT IS KNOWN AND OBJECTIVES: Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole...
February 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28176481/synergistic-activity-profile-of-an-antimicrobial-peptide-against-multidrug-resistant-and-extensively-drug-resistant-strains-of-gram-negative-bacterial-pathogens
#12
Simona Pollini, Jlenia Brunetti, Samanta Sennati, Gian Maria Rossolini, Luisa Bracci, Alessandro Pini, Chiara Falciani
Infection sustained by multidrug-resistant and extensively drug-resistant bacterial pathogens is often untreatable with the standard of care antibiotics, and the combination of anti-infective compounds often represents the only therapeutic strategy to face this major clinical treat. SET-M33 is a novel antimicrobial peptide (AMP) that has demonstrated in vitro and in vivo antimicrobial activity against Gram-negative bacteria and has shown interesting features in preclinical evaluations. Particularly, it showed efficacy against a number of multidrug-resistant and extensively drug-resistant clinical strains of Gram-negative pathogens, in in vitro and in vivo assessments...
February 8, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28173639/bosentan-and-rifampin-interactions-modulate-influx-transporter-and-cytochrome-p450-expression-and-activities-in-primary-human-hepatocytes
#13
Kyoung-Moon Han, Sun-Young Ahn, Hyewon Seo, Jaesuk Yun, Hye Jin Cha, Ji-Soon Shin, Young-Hoon Kim, Hyungsoo Kim, Hye-Kyung Park, Yong-Moon Lee
The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner...
February 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28167550/acquisition-of-rifampin-resistance-in-pulmonary-tuberculosis
#14
Xavier A Kayigire, Sven O Friedrich, Lize van der Merwe, Andreas H Diacon
Mycobacterium tuberculosis with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare and fixed drug combinations typically prevent augmentation of resistance. Fourteen newly diagnosed tuberculosis patients were treated with RIF only for 14 days and bacterial loads including mutation frequencies were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be resistant after 30 days of monotherapy, indicating that pharmacodynamic variation could contribute to the acquisition of resistance against RIF...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167549/polymyxin-b-based-triple-combinations-wage-war-against-kpc-2-producing-klebsiella-pneumoniae-new-dosing-strategies-for-old-allies
#15
Zackery P Bulman, Michael J Satlin, Liang Chen, Barry N Kreiswirth, Beom Soo Shin, Thomas J Walsh, Patricia N Holden, Alan Forrest, Roger L Nation, Jian Li, Brian T Tsuji
Pharmacodynamics of a polymyxin B, meropenem and rifampin triple combination were examined against Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) ST258. In time-kill experiments against three KPC-Kp isolates, triple combination generated 8.14, 8.19 and 8.29 log10CFU/mL reductions within 24h. In the hollow fiber infection model, the triple combination caused maximal killing of 5.16 log10CFU/mL at 78h and time required for regrowth was more than doubled versus 2-drug combinations...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167538/application-of-physiologically-based-pharmacokinetic-modeling-to-understanding-of-bosutinib-pharmacokinetics-prediction-of-drug-drug-and-drug-disease-interactions
#16
Chiho Ono, Poe-Hirr Hsyu, Richat Abbas, Cho-Ming Loi, Shinji Yamazaki
Bosutinib (Bosulif®) is an orally available Src/Abl tyrosine kinase inhibitor indicated for the treatment of patients with Ph+ chronic myelogenous leukemia. Bosutinib is predominantly metabolized by CYP3A4 as the primary clearance mechanism. The main objectives of the present study were to: 1) develop physiologically-based pharmacokinetic (PBPK) models of bosutinib, 2) verify and refine the PBPK models based upon clinical study results of bosutinib single-dose drug-drug interaction (DDI) with ketoconazole and rifampin, and single-dose drug-disease interaction (DDZI) in patients with renal and hepatic impairment, 3) apply the PBPK models to predict DDI outcome in patients with weak and moderate CYP3A inhibitors, and 4) apply the PBPK models to predict DDZI outcomes in renally and hepatically impaired patients after multiple-dose administration...
February 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28166721/early-interventions-for-diabetes-related-tuberculosis-associate-with-hastened-sputum-microbiological-clearance-in-virginia-usa
#17
Yosra Alkabab, Suzanne Keller, Denise Dodge, Eric Houpt, Deborah Staley, Scott Heysell
BACKGROUND: Diabetes complicates tuberculosis (TB) treatment including a prolonged time of sputum culture conversion to negative growth. Since 2013 in Virginia, interventions early in the treatment course have used therapeutic drug monitoring and dose correction for isoniazid and rifampin after 2 weeks of TB treatment in patients with diabetes along with nurse manager initiated diabetes education and linkage to care. METHODS: A retrospective cohort study of the state TB registry was performed for patients initiating drug-susceptible pulmonary TB treatment that were matched for age, gender, chest imaging and sputum smear status to compare time to sputum culture conversion and other clinical outcomes in the pre-and post-intervention groups...
February 6, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28161484/twenty-year-experience-with-aorto-enteric-fistula-repair-gastrointestinal-complications-predict-mortality
#18
Atish Chopra, Lucyna Cieciura, J Gregory Modrall, R James Valentine, Jayer Chung
BACKGROUND: Aorto-enteric fistulae (AEF) represent a lethal subset of aortic graft infections. The optimal management of AEF remains unclear. We aimed to identify predictors of morbidity and mortality. STUDY DESIGN: We performed a single-center retrospective review of consecutive AEF repairs. Demographics, co-morbidities, and peri-operative variables were obtained. Descriptive statistics, Chi-squared, Kruskall-Wallis, and Cox proportional-hazards modeling were utilized where appropriate...
February 1, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28161038/treatment-of-infections-caused-by-rhodococcus-equi
#19
REVIEW
Steeve Giguère
Pneumonia caused by Rhodococcus equi remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin remains the recommended therapy for foals with clinical signs of infection caused by R equi. Most foals with small, subclinical ultrasonographic pulmonary lesions associated with R equi recover without therapy, and administration of antimicrobial agents to these subclinically affected foals does not hasten lesion resolution relative to administration of a placebo...
February 1, 2017: Veterinary Clinics of North America. Equine Practice
https://www.readbyqxmd.com/read/28155817/impact-of-the-genexpert-mtb-rif-technology-on-tuberculosis-control
#20
Wendy Susan Stevens, Lesley Scott, Lara Noble, Natasha Gous, Keertan Dheda
Molecular technology revolutionized the diagnosis of tuberculosis (TB) with a paradigm shift to faster, more sensitive, clinically relevant patient care. The most recent molecular leader is the GeneXpert MTB/RIF assay (Xpert) (Cepheid, Sunnyvale, CA), which was endorsed by the World Health Organization with unprecedented speed in December 2010 as the initial diagnostic for detection of HIV-associated TB and for where high rates of drug resistance are suspected. South Africa elected to take an aggressive smear replacement approach to facilitate earlier diagnosis and treatment through the decision to implement the Xpert assay nationally in March 2011, against the backdrop of approximately 6...
January 2017: Microbiology Spectrum
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