The ability of cefotaxime, ciprofloxacin, piperacillin and tobramycin
to cause release of endotoxin was examined in vitro with cultures of E
nterobacter cloacae and Escherichia coli. Endotoxin was measured by a
quantitative limulus amoebocyte lysate assay and its presence was conf
irmed by silver staining of the lipopolysaccharide moiety following SD
S-PAGE. The morphology of the bacteria during antibiotic exposure was
examined by scanning electronmicroscopy. Cefotaxime, ciprofloxacin and
piperacillin caused significant endotoxin release, correlating with t
heir ability to affect cell-wall morphology, causing filamentation, wa
ll breakage and cell lysis. In contrast, little endotoxin was released
when bacteria were exposed to tobramycin and no morphological changes
were observed when bacteria were exposed to bactericidal concentratio
ns of this aminoglycoside. Its antimicrobial spectrum and bactericidal
activity make tobramycin an appropriate agent for treatment of sepsis
caused by gram-negative bacteria and its lack of propensity to elicit
excessive release of endotoxin may avoid exacerbation of endotoxin-re
lated shock in sepsis.