Effects of antibiotic class on the macrophage inflammatory response to Streptococcus pneumoniae

Antibiotic choice can alter host inflammation during invasive bacterial inf ections. Previous studies of gram-negative organisms concluded that antibio tic-mediated release of bacterial cell wall components amplifies inflammati on. Less has been reported about antibiotic effect on gram-positive organis ms. This study explored the hypothesis that Streptococcus pneumoniae would induce greater macrophage inflammatory mediator production when killed with cell wall active antibiotics rather than protein synthesis inhibitors. Sti mulation of RAW 264.7 murine macrophages with pneumococci and oxacillin led to significantly higher inducible nitric oxide synthase (iNOS) and tumor n ecrosis factor (TNF) accumulation than did the same concentrations of pneum ococci and clindamycin, Neither antibiotic alone or in combination with lip opolysaccharide acted directly on macrophages to modify the immune response . Endotoxin contamination did not confound the results, as preincubation wi th polymyxin B did not change iNOS or TNF protein levels. Thus, the antimic robial mechanism of action affects macrophage inflammatory mediator product ion after stimulation with pneumococci.