期刊
JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 1, 页码 75-82出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit129
关键词
Staphylococcus aureus; MRSA; protein synthesis inhibitor; linezolid; vancomycin; treatment; pneumonia; Panton-Valentine leukocidin; alpha-hemolysin; rabbit model
资金
- Pfizer
- US Public Health Service [NIH NIAID R01 AI087674]
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 alpha-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.
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