CLINICAL-SIGNIFICANCE OF ANTIBIOTIC ENDOTOXIN-RELEASING PROPERTIES INTRAUMA PATIENTS

Objective: To test the hypothesis that antibiotics leading to greater endotoxin release are associated with greater mortality in septic trau ma patients. Design: Post hoc analysis of data from a previously condu cted prospective, randomized, multicenter study designed to evaluate t he efficacy of interferon gamma in preventing infection and death in t rauma patients. Setting: Nine level I trauma centers. Patients: Severe ly injured trauma patients at high risk for sepsis. Eighty percent (N= 334) of the enrolled patients developed some manifestation of gram-neg ative sepsis, defined by the administration of gram-negative specific antibiotics. Main Outcome Measures: The in-hospital mortality rate of patients who received penicillin-binding protein 3/tumor necrosis fact or (PBP3/TNF)-specific antibiotics associated with the greatest degree of endotoxin release and TNF production (PBP3/TNF group, n=78: aztreo nam, ceftazidime, and cefotaxime sodium) was compared with that of pat ients not receiving these agents (non-PBP3/TNF group, n=256). Results: Mortality in the PBP3/TNF group (17%) was higher than in the non-PBP3 /TNF group (8%, P=.02). The two groups were similar in their mean (+/- SD) Injury Severity Scores (34+/-19), ages (31+/-12 years), and initia l degree of bacterial contamination. Conclusions: Antibiotics that are associated with greater release of endotoxin and production of TNF ar e also associated with greater mortality in septic trauma patients. De cisions regarding antibiotic administration may need to consider the e ndotoxin-releasing properties of antibiotics in addition to their anti bacterial sensitivity spectrum. Prospective studies of the effect of e ndotoxin-releasing properties of antibiotics on mortality are warrante d.