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J Infect Dis. 2013 Jul;208(1):75-82. doi: 10.1093/infdis/jit129. Epub 2013 Mar 26.

Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia.

Author information

1
Division of Infectious Diseases, Department of Medicine, University of California-San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. bdiep@medsfgh.ucsf.edu

Abstract

BACKGROUND:

 Linezolid is recommended for treatment of pneumonia and other invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The premise underlying this recommendation is that linezolid inhibits in vivo production of potent staphylococcal exotoxins, including Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla), although supporting evidence is lacking.

METHODS:

 A rabbit model of necrotizing pneumonia using MRSA clone USA300 was used to compare therapeutic effects of linezolid (50 mg/kg 3 times/day) and vancomycin (30 mg/kg 2 times/day) administered 1.5, 4, and 9 hours after infection on host survival outcomes and in vivo bacterial toxin production.

RESULTS:

 Mortality rates were 100% for untreated rabbits and 83%-100% for vancomycin-treated rabbits. In contrast, mortality rates were 25%, 50%, and 100% for rabbits treated with linezolid 1.5, 4, and 9 hours after infection, respectively. Compared with untreated and vancomycin-treated rabbits, improved survival of rabbits treated 1.5 hours after infection with linezolid was associated with a significant decrease in bacterial counts, suppressed bacterial production of PVL and Hla, and reduced production of the neutrophil-chemoattractant interleukin 8 in the lungs.

CONCLUSIONS:

 Across the study interval, only early treatment with linezolid resulted in significant suppression of exotoxin synthesis and improved survival outcomes in a rabbit model of MRSA necrotizing pneumonia.

KEYWORDS:

MRSA; Panton-Valentine leukocidin; Staphylococcus aureus; alpha-hemolysin; linezolid; pneumonia; protein synthesis inhibitor; rabbit model; treatment; vancomycin

PMID:
23532096
PMCID:
PMC3666136
DOI:
10.1093/infdis/jit129
[Indexed for MEDLINE]
Free PMC Article

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