Release of endotoxin from bacteria exposed to ciprofloxacin and its prevention with polymyxin B

An in vitro system for studying the phenomenon of antibiotic-induced release of endotoxin from gram-negative bacteria is described. Endotoxin was measured by a quantitative limulus lysate microassay. Using a strain of Escherichia coli, ciprofloxacin was shown to cause an immediate and sustained increase in endotoxin release compared to control cultures whereas gentamicin did not, despite an equally rapid bactericidal effect. The potential value of the anti-endotoxin effect of polymyxin B was examined using a polymyxin B resistant strain of Klebsiella aerogenes. Ciprofloxacin alone caused endotoxin release, but when given with polymyxin B significantly less endotoxin was detected. These results indicate that in antibiotic-induced endotoxin release, the rate of cell death is less important than the site of antibiotic effect, and suggest that ciprofloxacin may act directly on the cell wall as well as on DNA gyrase. It is possible that polymyxin B could be used to reduce the extent of endotoxin release, and that this would be of clinical benefit.