211 ENDOTOXIN LIBERATION DURING THERAPY FOR GRAM-NEGATIVE BACTERIAL SEPSIS

Abstract

To determine if plasma levels of free endotoxin increase during the initial hours of antibiotic therapy for gram-negative bacterial sepsis, serial blood samples were obtained from 24 patients presenting with suspected sepsis. For each sample the level of bacteremia was determined by quantitative culture, and the levels of free (filterable) and bacterial cell-bound plasma endotoxin were measured by Limulus lysate assay. Fourteen patients had no detectable bacteremia or endotoxemia. Five patients with constant or declining levels of free endotoxemia had transient gram-negative bactereraia (2), no detectable bacteremia (2), or overwhelming gram-positive bacterial sepsis (1). The remaining five patients had gram-negative bacterial sepsis ranging from 30 to 107 cfu/ml blood. Plasma free endotoxin increased in all of these patients during the initial hours of antibiotic therapy, while levels of bacteremia and cell-bound endotoxin were decreasing. Plasma free endotoxin subsequently cleared in four of these patients, but continued to rise in the other patient, associated with progressive purpura fulminans and irreversible shock. These results are consistent with the hypothesis that antibioticinduced endotoxin release may be responsible for the deterioration observed in some patients with gram-negative bacterial sepsis during antibiotic therapy.