COMBINATION TREATMENTS USING VANCOMYCIN WITH IMMUNOMODULATORS TO MODULATE STAPHYLOCOCCAL ARTHRITIS
Abstract
ABSTRACT
Objective: Staphylococcus aureus is an intensely studied organism to cause septic arthritis. This study aims at using vancomycin to mitigate the
bacterial burden in mice infected with pathogenic strain of S. aureus which is combined with the in vivo inhibition of nitric oxide (NO) and prostaglandin
(PG) levels via aminoguanidine (AMG) and meclofenamic acid (MFA), respectively, to modulate the inflammatory conditions in bacterial arthritis.
Methods: Synergy between the drugs was performed via Chequerboard. The clinical signs of septic arthritis were recorded on the 3
days
post-infection (DPI) including induction of arthritis, measuring bacterial density in blood, spleen and synovial tissue, blood parameters and cytokines
(tumor necrosis factor alpha (TNF α), interferon gamma (IFN γ), interleukin-6 [IL-6], IL-10) levels, myeloperoxidase (MPO) and lysozyme activities,
and histopathological examinations of the synovial joints.
Results: S. aureus infection showed a significant increase in bacterial densities and inflammation. AMG/MFA treatment alone showed no bacterial
clearance since endogenous NO or PG had been limited for bacterial killing but observably down-regulated inflammatory upshots. Vancomycin cotreatment
with
AMG
or
MFA
showed
maximum mitigation
of
bacterial
load as well
as
the inflammatory
conditions,
articular
repair
and decreased
in
the
percentage
of induction of arthritis.
Conclusion: Diminution of S. aureus burden in tissues via vancomycin and suppression of inflammatory by AMG or MFA may have shown a visibly
potent therapeutic remedy to combat septic arthritis.
Keywords: Aminoguanidine, Meclofenamic acid, Septic arthritis, Staphylococcus aureus, Vancomycin
rd
, 9
th
, and 15
th
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