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Jordan R Smith, Juwon Yim, Seth Rice, Kyle Stamper, Razie Kebriaei, Michael J Rybak
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for healthcare-associated infections, and treatment options are limited. Tedizolid (TZD), is a novel, oxazolidinone antibiotic with activity against MRSA. Previously, daptomycin (DAP), has demonstrated synergy with other antibiotics against MRSA. We sought to determine the efficacy of the combination of TZD + DAP against MRSA in an in vitro model of simulated endocardial vegetations (SEVs). Methods: TZD simulations of 200 mg once daily and DAP simulations of 6-mg/kg and 10-mg/kg once daily were tested alone and in the combinations of TZD + DAP 6-mg/kg or DAP 10-mg/kg against two clinical strains of MRSA, 494 and 67...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Hiroshige Mikamo, Yoshio Takesue, Yuji Iwamoto, Takahiko Tanigawa, Masaharu Kato, Yoko Tanimura, Shigeru Kohno
The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs) and/or for 7-21 days for those with SSTI-related bacteraemia, caused by confirmed or highly suspected methicillin-resistant Staphylococcus aureus (MRSA). Primary outcome was clinical cure rate at test-of-cure (TOC, in SSTI: 7-14 days, in bacteraemia: 4-6 weeks after end-of-therapy [EOT]) time point in the microbiologically evaluable MRSA (ME-MRSA) population (N = 39)...
March 9, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Cathy Hardalo, Thomas P Lodise, Monique Bidell, Shawn Flanagan, Carisa De Anda, Steven Anuskiewicz, Philippe Prokocimer
BACKGROUND: We evaluated safety and tolerability of tedizolid phosphate at the 200-mg once-daily dose approved for 6-day treatment of skin and skin-structure infections. RESEARCH DESIGN AND METHODS: Clinical adverse event (AE) and laboratory data were pooled across completed clinical studies (13 phase 1, two phase 2, and two phase 3), for all participants who received ≥1 dose of tedizolid 200 mg, linezolid 600 mg (phase 3 only), or placebo (phase 1 only). RESULTS: 1280 participants received tedizolid (phase 1: n = 355; phase 2/3: n = 925)...
March 12, 2018: Expert Opinion on Drug Safety
Ana Alejandra García Robles, Eduardo López Briz, María Dolores Fraga Fuentes, Rocío Asensi Diez, Jesús Francisco Sierra Sánchez
OBJECTIVE: To assess critically oritavancin, a second-generation  lipoglycopeptide, for the treatment of Acute Bacterial Skin and Skin Structure Infections caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. METHOD: An evaluation report of oritavancin in Acute Bacterial Skin and Skin  Structure Infections was carried out according to the methodology of the Group  for drug evaluation, standardization and research in drug selection of the  Spanish Society of Hospital Pharmacy (SEFH)1, with the MADRE 4...
March 1, 2018: Farmacia Hospitalaria
Pierre Delpech, Muna ALeryan, Brian Jones, Curtis Gemmell, Sue Lang
Skin and soft tissue infections (SSTI) are among the most commonly occurring infections and evidence suggests that these are increasing world-wide. The aetiology is diverse, but Staphylococcus aureus predominate and these are often resistant to antimicrobials that were previously effective. Tedizolid is a new oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI caused by Gram-positive pathogens, including S. aureus. The aim of this study was to evaluate the in vitro efficacy of tedizolid in comparison to other clinically used antibacterials against antibiotic sensitive- and resistant-staphylococci, grown in planktonic cultures and as biofilms reflecting the growth of the microorganism during episodes of SSTI...
January 10, 2018: Diagnostic Microbiology and Infectious Disease
Ana R Freitas, Aziz R Dilek, Luísa Peixe, Carla Novais
No abstract text is available yet for this article.
February 12, 2018: Infection Control and Hospital Epidemiology
Bing Bai, Kaitao Hu, Hui Li, Weiming Yao, Duoyun Li, Zhong Chen, Hang Cheng, Jinxin Zheng, Weiguang Pan, Minggui Deng, Xiaojun Liu, Zhiwei Lin, Qiwen Deng, Zhijian Yu
Enterococcal infections have become one of the most challenging nosocomial problems. Tedizolid, the second oxazolidinone is four- to eight-fold more potent in vivo and in vitro than linezolid against enterococci. However, the characteristics of tedizolid related to enterococci isolates in China remain elusive. The aim of this study was to evaluate in vitro activity of tedizolid against enterococcal isolates from patients with infections at a teaching hospital in China and to investigate the correlations between in vitro tedizolid activity against enterococci and the distribution of multilocus sequence types (MLST), resistance genes, and virulence factors...
December 27, 2017: FEMS Microbiology Letters
Carisa De Anda, Steven Anuskiewicz, Philippe Prokocimer, Jose Vazquez
BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. METHODS: Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens...
December 2017: Medicine (Baltimore)
Matthieu Grégoire, Julia Brochard Libois, Denis Waast, Benjamin Gaborit, Marc Dauty, Guillaume Deslandes, Eric Dailly, Sophie Touchais, David Boutoille, Nicolas Grégoire, William Couet
An obese woman was treated orally by tedizolid 200 mg once daily for a pseudoarthrosis, 10 years after a Roux-en-Y bypass surgery.Total plasma peak concentration was 2.12 mg/L, 3h after intake and AUC0-24h was 28.3 mg/L*h. The AUC0-24h/MIC ratio for unbound concentrations and for sensible Staphylococcus and Streptococcus strains was at least 10.8, higher than a targeted ratio of 3.These results support the use of tedizolid without adjustment after a bariatric surgery.
January 29, 2018: Antimicrobial Agents and Chemotherapy
Masayuki Nigo, Andrea M Luce, Cesar A Arias
No abstract text is available yet for this article.
January 23, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Emilio Bouza, Patricia Muñoz, Almudena Burillo
PURPOSE OF REVIEW: Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects...
April 2018: Current Opinion in Infectious Diseases
Matteo Bassetti, Antionio Vena, Nadia Castaldo, Elda Righi, Maddalena Peghin
PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) bacteria represents a global emerging problem. Delayed prescription of an adequate treatment for VAP has been associated with higher morbidity and mortality. New molecules have been developed to face the need of compounds that are active against resistant Gram-positive and Gram-negative pathogens. The aim of this review is to summarize the current scenario of new therapeutic options for the treatment of VAP...
April 2018: Current Opinion in Infectious Diseases
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 ( 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
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
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
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
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 MIC50 s and MIC90 s 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...
March 2018: Diagnostic Microbiology and Infectious Disease
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
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
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
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