Abstract
Although early antibiotic treatment of patients with septic arthritis eradicates bacteria, joint destruction commonly results from the unregulated host inflammatory responses to infection. The spin trap compound phenyl-N-tert-butyl nitrone (PBN) has been shown to have both anti-inflammatory and antioxidant effects. The aim of this study was to assess the effect of combined systemic administration of PBN and cloxacillin on the development of Staphylococcus aureus arthritis.Three days after Naval Medical Research Institute (NMRI) mice were infected intravenously with S. aureus LS-1, daily treatment was started with cloxacillin alone, PBN alone, or cloxacillin and PBN. Arthritis, weight loss and general condition were evaluated for each mouse, and joints were analyzed histopathologically. Systemic administration of PBN in conjunction with cloxacillin ameliorated the course of experimental S. aureus arthritis, as evidenced by an increased cure rate. Thus, combinatorial antioxidant plus antibiotic anti-inflammatory therapies represent a potentially efficacious approach to the management of septic arthritis.
Highlights
Staphylococcus aureus is the most common causative agent of septic arthritis [1,2,3], a severe, rapidly progressing, erosive disease with high morbidity and mortality
We have previously shown that antibacterial therapy combined with systemic corticosteroid administration ameliorated S. aureus arthritis in mice [6]
We evaluated the efficacy of a combined phenyl-Ntert-butyl nitrone (PBN) and antibiotic treatment in reducing joint destruction during staphylococcal arthritis in a murine model of hematogenously spread S. aureus sepsis and septic arthritis [8,9]
Summary
Staphylococcus aureus is the most common causative agent of septic arthritis [1,2,3], a severe, rapidly progressing, erosive disease with high morbidity and mortality. Inflammatory processes during septic arthritis erode articular cartilage, destroy bone and promote joint destruction leading to irreversible loss of joint function in 25–50% of patients [4,5]. Administration of antibiotics eradicates the bacteria, but does not stop joint destruction. We have previously shown that antibacterial therapy combined with systemic corticosteroid administration ameliorated S. aureus arthritis in mice [6]. The compound α-phenyl-Ntert-butyl nitrone (PBN) was originally developed as a means of trapping and detecting free radical intermediates [7]. PBN and related nitrones have a variety of anti-inflammatory and antioxidant properties. We evaluated the efficacy of a combined PBN and antibiotic (cloxacillin) treatment in reducing joint destruction during staphylococcal arthritis in a murine model of hematogenously spread S. aureus sepsis and septic arthritis [8,9]
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