Einfluss von Moxifloxacin auf die Endotoxinfreisetzung aus Escherichia coli und Bacteroides fragilis im Vergleich zu anderen Antibiotika

Abstract

Background: Bacterial endotoxin is known to act as a potent trigger of disseminated coagulation and septic shock. During clinical antibiotic treatment, endotoxin may be released from gram-negativ bacteria. It is well established that antibiotic classes differ in their ability to induce endotoxin release. Aim: To test the endotoxin-liberating potential of different antibiotics with activity against Escherichia coli and Bacteroides fragilis. Methods: In vitro test models were used to evaluate the endotoxin-liberating potential of moxifloxacin, a fourth generation quinolone with antianaerobic activity and to compare with other antibiotic agents. Comparator drugs were ceftazidime/cefoxitin and imipenem, i.e. antibiotics with known high and low endotoxin-liberating potential, respectively. Bacteria were exposed to moxifloxacin at 2 x, 10 x and 50 x of the minimal inhibitory concentration (MIC). Endotoxin release was measured by enzyme-linked immunosorbent (ELISA) and Limulus amoebocyte lysate (LAL) assay. As a parameter for biological responses to endotoxin, the release of the proinflammatory cytokines TNFalpha- and IL-1beta from the human monocytes Mono Mac 6 was quantified with bioassays. The morphological correlation to the endotoxin liberation was examined by phase contrast microscopy. Results: In all test systems, release of endotoxin during exposure of bacteria to moxifloxacin was minimal or low and comparable to that of imipenem. The endotoxin of Bacteroides fragilis was not detectable by the used tests. Relating to the bacterial morphology it arose that the influence of moxifloxacin induced the formation of roundish bacterial cells, called spheroplasts, just as the influence of imipenem. Conclusions: Moxifloxacin has a low potential to cause endotoxin-mediated detrimental clinical effects. Concerning its endotoxin-releasing properties, moxifloxacin appears to be a choice equivalent to the carbapenems.