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https://www.readbyqxmd.com/read/29319932/pharmacokinetics-safety-and-tolerability-of-tedizolid-phosphate-in-elderly-subjects
#1
Shawn D Flanagan, Sonia L Minassian, Philippe Prokocimer
Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infections in adults. We evaluated the pharmacokinetics of tedizolid in elderly subjects to guide dosing recommendations. In an open-label phase 1 study (ClinicalTrials.gov identifier NCT01496677), 14 elderly (≥65 years) and 14 younger control (18-45 years) subjects each received a single oral dose of tedizolid phosphate 200 mg. Blood samples were collected before dose and more than 72 hours after dose. The pharmacokinetic parameters of tedizolid after a single dose were similar in both age groups...
January 10, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29300156/comparative-activity-of-tedizolid-and-glycopeptide-combination-therapies-for-the-treatment-of-staphylococcus-aureus-infections-an-in-vitro-and-in-vivo-evaluation-against-strains-with-reduced-susceptibility-to-glycopeptides
#2
J W Betts, H F Abdul Momin, L M Phee, D W Wareham
PURPOSE: Glycopeptides are widely used for the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infections. Although difficult to detect, isolates with reduced (GISA), hetero (hGISA) or complete (GRSA) resistance to glycopeptides are increasingly reported. Optimal therapy for such strains is unknown. We compared the in vitro and in vivo activity of tedizolid (TED), a recently licensed oxazolidonone, with vancomycin (VAN) and teicoplanin (TEIC) combined with fusidic acid (FD) or rifampicin (RIF) against S...
January 4, 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29290374/physical-compatibility-of-meropenem-and-vaborbactam-with-select-intravenous-drugs-during-simulated-y-site-administration
#3
James M Kidd, Lindsay M Avery, Tomefa E Asempa, David P Nicolau, Joseph L Kuti
PURPOSE: Meropenem/vaborbactam is a novel intravenous antibiotic combining the carbapenem, meropenem, with a novel β-lactamase inhibitor, vaborbactam. Meropenem/vaborbactam is administered as a 3-hour infusion given every 8 hours, thereby potentially restricting an intravenous line for 9 h/d. Intravenous medications may be given concurrently via Y-site when compatibility data are available. Herein, physical compatibility was determined for the identification which medications can be coadministered with meropenem/vaborbactam via Y-site...
December 28, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29277464/determination-of-tedizolid-susceptibility-interpretive-criteria-for-gram-positive-pathogens-according-to-clinical-and-laboratory-standards-institute-guidelines
#4
Mekki Bensaci, Shawn Flanagan, Taylor Sandison
For effective antibacterial therapy, physicians require qualitative test results using susceptibility breakpoints provided by clinical microbiology laboratories. This article summarizes the key components used to establish the Clinical Laboratory Standards Institute (CLSI) breakpoints for tedizolid. First, in vitro studies using recent surveillance and clinical trial isolates ascertained minimal inhibitory concentration (MIC) distributions against pertinent organisms, including staphylococci, streptococci, and enterococci...
November 7, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29217419/in-vitro-activity-of-tedizolid-against-the-mycobacterium-abscessus-complex
#5
Fabrice Compain, Daria Soroka, Beate Heym, Jean-Louis Gaillard, Jean-Louis Herrmann, Delphine Dorchène, Michel Arthur, Vincent Dubée
Infections due to Mycobacterium abscessus carry a poor prognosis since this rapidly growing mycobacterium is intrinsically resistant to most antibiotics. Here, we evaluate the in vitro activity of the new oxazolidinone tedizolid against a collection of 44M. abscessus clinical isolates. The MIC50s and MIC90s of tedizolid (2 and 8μg/mL, respectively) were 2- to 16-fold lower than those of linezolid. There was no difference between the 3M. abscessus subspecies. Time-kill assays did not show any bactericidal activity at 4- and 8-fold the MIC...
November 10, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29173791/new-antimicrobial-agents-for-the-treatment-of-staphylococcal-infections-in-children
#6
REVIEW
Roopali Sharma, Densley Francois, Margaret R Hammerschlag
Several new antimicrobial agents-daptomycin, ceftaroline, telavancin, dalbavancin, and-tedizolid have been approved for the treatment of staphylococcal infections, including methicillin-resistant Staphylococcus aureus (MRSA), in adults. Ceftaroline and daptomycin have been approved by the US Food and Drug Administration for use in children. Ceftaroline, a beta-lactam antibiotic with activity against MRSA, has been approved for treatment of community-acquired bacterial pneumonia and complicated skin and skin structure infections...
December 2017: Pediatric Clinics of North America
https://www.readbyqxmd.com/read/29109162/comparative-assessment-of-tedizolid-pharmacokinetics-and-tissue-penetration-between-diabetic-patients-with-wound-infections-and-healthy-volunteers-via-in-vivo-microdialysis
#7
Sean M Stainton, Marguerite L Monogue, Arlinda Baummer-Carr, Ashley K Shepard, James F Nugent, Joseph L Kuti, David P Nicolau
Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200mg every 24 hours for 3 doses to achieve steady-state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the 3(rd) dose, 12 blood and 14 dialysate fluid samples were collected over 24 hours to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue...
November 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29103695/distribution-of-optra-and-cfr-in-florfenicol-resistant-staphylococcus-sciuri-of-pig-origin
#8
Run Fan, Dexi Li, Andrea T Feßler, Congming Wu, Stefan Schwarz, Yang Wang
A novel transferable oxazolidinone-phenicol resistance gene, optrA, which confers resistance to linezolid, the next-generation oxazolidinone tedizolid, and also to chloramphenicol and florfenicol, has been identified in enterococcal and staphylococcal species. Here, we investigated the epidemiology of optrA in florfenicol-resistant Staphylococcus spp. isolates of pig origin, and characterized the genetic context of oxazolidinone resistance genes in 20 optrA-positive florfenicol- and methicillin-resistant S...
October 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29063519/clinical-pharmacokinetics-and-pharmacodynamics-of-oxazolidinones
#9
REVIEW
Claire Roger, Jason A Roberts, Laurent Muller
Oxazolidinones are a class of synthetic antimicrobial agents with potent activity against a wide range of multidrug-resistant Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Oxazolidinones exhibit their antibacterial effects by inhibiting protein synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing formation of a functional 70S initiation complex. Currently, two oxazolidinones have been approved by the US Food and Drug Administration: linezolid and more recently tedizolid...
October 23, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29038274/thrombocytopenia-with-tedizolid-and-linezolid
#10
Erica Yookyung Lee, Aisling Caffrey
Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved 06/2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration Adverse Event Reporting System (07/2014-12/2016), we observed a significantly increased risk of thrombocytopenia of similar magnitude with both antibiotics: linezolid reporting odds ratio [ROR] 37.9 (95% confidence interval [CI] 20.78-69.17); tedizolid ROR 34...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29029072/detection-of-optra-in-the-african-continent-tunisia-within-a-mosaic-enterococcus-faecalis-plasmid-from-urban-wastewaters
#11
Ana R Freitas, Houyem Elghaieb, Ricardo León-Sampedro, Mohamed Salah Abbassi, Carla Novais, Teresa M Coque, Abdennaceur Hassen, Luisa Peixe
Objectives: Oxazolidinone resistance is a serious limitation in the treatment of MDR Enterococcus infections. Plasmid-mediated oxazolidinone resistance has been strongly linked to animals where the use of phenicols might co-select resistance to both antibiotic families. Our goal was to assess the diversity of genes conferring phenicol/oxazolidinone resistance among diverse enterococci and to characterize the optrA genetic environment. Methods: Chloramphenicol-resistant isolates (>16 mg/L, n = 245) from different sources (hospitals/healthy humans/wastewaters/animals) in Portugal, Angola and Tunisia (1996-2016) were selected...
September 26, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28942574/once-daily-treatments-for-methicillin-susceptible-staphylococcus-aureus-bacteremia-are-they-good-enough
#12
REVIEW
Sylvain A Lother, Natasha Press
PURPOSE OF THE REVIEW: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a common cause of morbidity and mortality. First-line treatment requires frequent daily doses of an anti-staphylococcal beta-lactam. However, some physicians prescribe simpler once-daily regimens to improve compliance and improve healthcare utilization. We reviewed the literature regarding advantages, pitfalls, and efficacy of once-daily treatment options for MSSA bacteremia. RECENT FINDINGS: Several once-daily antibiotics are effective in vitro against MSSA (ceftriaxone, daptomycin, telavancin, dalbavancin, oritavancin, tedizolid, ertapenem, fluoroquinolones, and others), but there is insufficient evidence to support these agents for MSSA bacteremia...
September 23, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28923878/in-vitro-susceptibility-testing-of-tedizolid-against-isolates-of-nocardia
#13
Barbara A Brown-Elliott, Richard J Wallace
There is a paucity of efficacious antimicrobials (especially oral) against clinically relevant species of Nocardia To date, all species of Nocardia have been susceptible to linezolid, the first commercially available oxazolidinone. Tedizolid is a new oxazolidinone with previously reported improved in vitro and in vivo (intracellular) potency against multidrug resistant strains of Mycobacterium sp., and Nocardia brasiliensis Using the current Clinical and Laboratory Standards Institute recommended broth microdilution method, 101 isolates of Nocardia spp, including 29 N...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#14
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922807/tedizolid-is-highly-bactericidal-in-the-treatment-of-pulmonary-mycobacterium-avium-complex-disease
#15
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. Methods: We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28920854/in-vitro-activity-of-tedizolid-and-comparator-agents-against-gram-positive-pathogens-responsible-for-bone-and-joint-infections
#16
COMPARATIVE STUDY
Pauline Ract, Caroline Piau-Couapel, Fabrice Compain, Michel Auzou, Jocelyn Michon, Vincent Cattoir
Tedizolid, a second-generation oxazolidinone that displays a potent activity against Gram-positive pathogens, could be an interesting option for the treatment of bone and joint infections (BJIs). The aim of the study was to determine minimal inhibitory concentration (MIC) of tedizolid against a collection of 359 clinical isolates involved in clinically-documented BJIs and to compare them to those of comparator agents used in Gram-positive infections. Of the 104 Staphylococcusaureus and 102 coagulase-negative staphylococci (CoNS) isolates, 99 and 92 % were categorized as susceptible to tedizolid, respectively (MIC25=0...
October 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28920493/construction-and-evaluation-in-vitro-and-in-vivo-of-tedizolid-phosphate-loaded-cationic-liposomes
#17
Zhenlei Yang, Liu Tian, Jingjing Liu, Guihua Huang
Firstly, The SA-TDZA-Lips were prepared by reverse-phase evaporation method. Then, the drug release behavior was evaluated by dynamic membrane dialysis in vitro and the preliminary safety was evaluated by hemolysis method. Finally, with Tedizolid phosphate injection (TDZA-Inj) and tedizolid phosphate loaded liposomes (TDZA-Lips) as the control groups, the pharmacokinetic characteristic and tissues distribution of SA-TDZA-Lips were evaluated after intravenous injection. As a result, the stearylamine modified tedizolid phosphate liposomal delivery system was constructed successfully and the particle size was (194...
September 18, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28865799/pharmacokinetics-safety-and-tolerability-of-tedizolid-phosphate-after-single-dose-administration-in-healthy-korean-male-subjects
#18
Yun Kim, Anhye Kim, SeungHwan Lee, Sung-Hak Choi, Dae Young Lee, Ji-Su Song, Howard Lee, In-Jin Jang, Kyung-Sang Yu
PURPOSE: Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant Staphylococcus aureus. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects...
August 30, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28812924/susceptibility-testing-and-reporting-of-new-antibiotics-with-a-focus-on-tedizolid-an-international-working-group-report
#19
Mark H Wilcox, Natalia Dmitrieva, Ana Cristina Gales, Irina Petukhova, Suleiman Al-Obeid, Flavia Rossi, Joseph M Blondeau
Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics...
August 16, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28793964/in-vitro-activities-of-tedizolid-and-comparator-antimicrobial-agents-against-clinical-isolates-of-staphylococcus-aureus-collected-in-12-countries-from-2014-to-2016
#20
James A Karlowsky, Meredith A Hackel, Samuel K Bouchillon, Jeff Alder, Daniel F Sahm
Clinical isolates of Staphylococcus aureus (n=3929) collected by 54 medical center laboratories in 12 countries in 2014-2016 were tested for in vitro susceptibility to tedizolid, linezolid, and 11 comparators using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodology with minimum inhibitory concentrations (MICs) interpreted by CLSI M100-S26 (2016) criteria. All isolates of S. aureus tested were susceptible to both tedizolid (MIC, ≤0.5μg/mL) and linezolid (MIC, ≤4μg/mL). The concentration of tedizolid that inhibited 90% of isolates (MIC90) was 0...
July 8, 2017: Diagnostic Microbiology and Infectious Disease
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