Journal
PEDIATRIC RESEARCH
Volume 57, Issue 3, Pages 419-423Publisher
SPRINGERNATURE
DOI: 10.1203/01.PDR.0000153946.97159.79
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Streptococcus agalactiae (group B Streptococcus, GBS) is an important cause of sepsis and meningitis in neonates, and excessive production of the inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO) causes tissue injury during severe infections. We hypothesized that exposure of GBS to different antimicrobial agents would affect the magnitude of the macrophage inflammatory response to this organism. We stimulated RAW 264.7 murine macrophages with a type-la GBS isolate in the presence of ampicillin, cefotaxime, rifampin, clindamycin, or gentamicin, singly or in combination. We found that GBS exposed to rifampin or clindamycin (versus beta-lactam antibiotics) stimulated less TNF secretion and inducible nitric oxide synthase (iNOS) protein accumulation in RAW 264.7 cells. Furthermore, GBS exposed to combinations of antibiotics that included a protein synthesis inhibitor stimulated less macrophage TNF and iNOS production than did organisms exposed to beta-lactam antibiotics singly or in combination. We conclude that exposure of GBS to rifampin or clindamycin leads to a less pronounced macrophage inflammatory mediator response than does exposure of the organism to cell wall-active antibiotics.
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