Institute of Hospital Hygiene, Klinikum Stuttgart, Germany.
Chemotherapy. 2010;56(5):364-70. doi: 10.1159/000321622. Epub 2010 Oct 7.
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.
It was the aim of this study to test the endotoxin-liberating potential of different antibiotics with activity against Escherichia coli and Bacteroides fragilis.
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.
In all test systems, release of endotoxin during exposure of bacteria to moxifloxacin was minimal or low and comparable with that of imipenem.
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.
细菌内毒素已知可作为弥散性凝血和感染性休克的有效触发因素。在临床抗生素治疗期间,内毒素可能从革兰氏阴性菌中释放出来。已知抗生素类别在诱导内毒素释放的能力上有所不同。
本研究旨在测试针对大肠杆菌和脆弱拟杆菌具有活性的不同抗生素的内毒素释放潜力。
使用体外测试模型来评估具有抗厌氧菌活性的第四代喹诺酮类药物莫西沙星的内毒素释放潜力。细菌暴露于莫西沙星的最低抑菌浓度的 2×、10×和 50×。通过酶联免疫吸附试验和鲎变形细胞溶解物试验测量内毒素释放。比较药物为头孢他啶和亚胺培南,即分别具有高和低内毒素释放潜力的抗生素。作为对内毒素生物反应的参数,通过生物测定量化单核细胞/巨噬细胞中促炎细胞因子(肿瘤坏死因子-α、白细胞介素-1β)的释放。
在所有测试系统中,细菌暴露于莫西沙星时内毒素的释放最小或较低,与亚胺培南相当。
莫西沙星对内毒素介导的有害临床影响的潜力较低。就其释放内毒素的特性而言,莫西沙星似乎是一种与碳青霉烯类药物等效的选择。