Clinical significance of antibiotic endotoxin-releasing properties in trauma patients
C. N. Mock, G. J. Jurkovich, D. J. Dries and R. V. Maier
Department of Surgery, University of Washington, Seattle, USA.
OBJECTIVE: To test the hypothesis that antibiotics leading to greater
endotoxin release are associated with greater mortality in septic trauma
patients. DESIGN: Post hoc analysis of data from a previously conducted
prospective, randomized, multicenter study designed to evaluate the
efficacy of interferon gamma in preventing infection and death in trauma
patients. SETTING: Nine level I trauma centers. PATIENTS: Severely injured
trauma patients at high risk for sepsis. Eighty percent (N = 334) of the
enrolled patients developed some manifestation of gram-negative 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 factor (PBP3/TNF)-specific
antibiotics associated with the greatest degree of endotoxin release and
TNF production (PBP3/TNF group, n = 78: aztreonam, ceftazidime, and
cefotaxime sodium) was compared with that of patients 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
+/- 9), ages (31 +/- 12 years), and initial degree of bacterial
contamination. CONCLUSIONS: Antibiotics that are associated with greater
release of endotoxin and production of TNF are also associated with greater
mortality in septic trauma patients. Decisions regarding antibiotic
administration may need to consider the endotoxin-releasing properties of
antibiotics in addition to their antibacterial sensitivity spectrum.
Prospective studies of the effect of endotoxin-releasing properties of
antibiotics on mortality are warranted.
