THE SIGNIFICANCE OF ENDOTOXIN RELEASE IN EXPERIMENTAL AND CLINICAL SEPSIS IN SURGICAL PATIENTS - EVIDENCE FOR ANTIBIOTIC-INDUCED ENDOTOXIN RELEASE

Sepsis and peritonitis remain a serious challenge for surgical patient s, despite improvement in surgical therapy and intensive care and the introduction of new powerful antibiotics. Recent in vitro studies reve aled the potential of certain antibiotics, e.g. penicillin-binding pro tein (PBP) 3-specific antibiotics, to cause antibiotic-induced endotox in release. Other types of antibiotics, e.g., PBP 2-specific antibioti cs, were associated with no or less endotoxin release. Further in vitr o experiments and investigations in animals support the hypothesis of antibiotic-induced endotoxin release, but there is little clinical evi dence. The clinical significance of endotoxin is subject of open dispu te with many pro's and contra's. Endotoxin, although an important trig ger, may not be the only factor to induce cytokine release, e.g., pept idoglycans were able to stimulate cells to release cytokines. Gram-pos itive pathogens have gained more importance in clinical sepsis and may not be sufficiently reflected in current clinical studies. The hypoth esis that neutralization of endotoxin and proinflammatory cytokines is beneficial in sepsis was seriously challenged by the results of recen t clinical and experimental studies. The better understanding of mecha nisms in endotoxin-induced cell activation and cell, cell-receptor and soluble receptor interactions led to new treatment options. Recent re ports on the complex pathogenesis of peritonitis and the detection of pathogen-related factors,vith intraperitoneal immune response may have implications on clinical studies investigating the potential of new c ompounds and the effect of antibiotics on endotoxin release. However, only few reports are available on the clinical significance of antibio tic-induced endotoxin release, and association of endotoxin release wi th pathogens, mortality or alteration of physiological parameters were not observed. With regard to the particulars of these studies, e.g., a small study population or low mortality rate, mortality may not be a n ideal outcome parameter for these studies. There is clinical evidenc e for antibiotic-induced endotoxin release. However, the need for well -designed and performed studies using newly developed monitoring devic es in intensive care therapy is obvious.