Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia.

Autor:	Le VT; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Le HN; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Pinheiro MG; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Hahn KJ; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Dinh ML; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA., Larson KB; Merck & Co., Inc., Kenilworth, New Jersey, USA., Flanagan SD; Merck & Co., Inc., Kenilworth, New Jersey, USA., Badiou C; INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France.; Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France., Lina G; INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France.; Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France., Tkaczyk C; Department of Infectious Diseases, MedImmune, Gaithersburg, Maryland, USA., Sellman BR; Department of Infectious Diseases, MedImmune, Gaithersburg, Maryland, USA., Diep BA; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA binh.diep@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2017 Mar 24; Vol. 61 (4). Date of Electronic Publication: 2017 Mar 24 (Print Publication: 2017).
DOI:	10.1128/AAC.02734-16
Abstrakt:	The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily ( P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily ( P = 0.003) and 17% for rabbits treated with saline ( P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus -secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection. (Copyright © 2017 American Society for Microbiology.)
Databáze:	MEDLINE
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