Low Endotoxin Release from Escherichia coli and Bacteroides fragilis during Exposure to Moxifloxacin

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-negative bacteria. It is known that antibiotic classes differ in their ability to induce endotoxin release. Aim: It was the aim of this study 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 4th-generation quinolone with antianaerobic activity. Bacteria were exposed to moxifloxacin at 2×, 10× and 50× the minimal inhibitory concentration. Endotoxin release was measured by enzyme-linked immunosorbent and Limulus amoebocyte lysate assays. Comparator drugs were ceftazidime and imipenem, i.e. antibiotics with known high and low endotoxin-liberating potential, respectively. As a parameter for biological responses to endotoxin, the release of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β) from monocytes/macrophages was quantified with bioassays. Results: In all test systems, release of endotoxin during exposure of bacteria to moxifloxacin was minimal or low and comparable with that 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.