Sepsis and
peritonitis remain a serious challenge for surgical patients, despite improvement in surgical
therapy and
intensive care and the introduction of new powerful
antibiotics. Recent in vitro studies revealed the potential of certain
antibiotics, e.g.
penicillin-binding protein (PBP) 3-specific
antibiotics, to cause
antibiotic-induced
endotoxin release. Other types of
antibiotics, e.g., PBP 2-specific
antibiotics, were associated with no or less
endotoxin release. Further in vitro experiments and investigations in animals support the hypothesis of
antibiotic-induced
endotoxin release, but there is little clinical evidence. The clinical significance of
endotoxin is subject of open dispute with many pro's and contra's.
Endotoxin, although an important trigger, may not be the only factor to induce
cytokine release, e.g., peptidoglycans were able to stimulate cells to release
cytokines. Gram-positive pathogens have gained more importance in clinical
sepsis and may not be sufficiently reflected in current clinical studies. The hypothesis that neutralization of
endotoxin and pro-inflammatory
cytokines is beneficial in
sepsis was seriously challenged by the results of recent clinical and experimental studies. The better understanding of mechanisms in
endotoxin-induced cell activation and cell, cell-receptor and soluble receptor interactions led to new treatment options. Recent reports on the complex pathogenesis of
peritonitis and the detection of pathogen-related factors with intraperitoneal immune response may have implications on clinical studies investigating the potential of new compounds and the effect of
antibiotics on
endotoxin release. However, only few reports are available on the clinical significance of
antibiotic-induced
endotoxin release, and association of
endotoxin release with 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 an ideal outcome parameter for these studies. There is clinical evidence for
antibiotic-induced
endotoxin release. However, the need for well-designed and performed studies using newly developed monitoring devices in
intensive care therapy is obvious.