Shenep J L, Barton R P, Mogan K A
J Infect Dis. 1985 Jun;151(6):1012-8. doi: 10.1093/infdis/151.6.1012.
To evaluate the role of antibiotic class in the rate of liberation of endotoxin during therapy for sepsis caused by gram-negative bacteria, we obtained serial blood samples from rabbits with sepsis caused by Escherichia coli and treated with chloramphenicol, gentamicin, or moxalactam. The concentrations of viable bacteria, free endotoxin, and total endotoxin in each blood sample were measured. In rabbits treated with chloramphenicol, the geometric mean levels of free endotoxin remained proportional to the geometric mean levels of bacteremia, a result indicating the absence of antibiotic-induced endotoxin liberation. In contrast, levels of free endotoxin increased rapidly while levels of bacteremia declined after treatment with gentamicin or moxalactam, a result indicating antibiotic-induced release of endotoxin. Despite similar rates of bacterial killing, mean levels of free endotoxin were as much as 20-fold higher in rabbits treated with moxalactam than in paired rabbits receiving gentamicin (P less than .05). These results indicate that endotoxin liberation during therapy for sepsis caused by gram-negative bacteria is dependent upon the class of antibiotic administered and is not necessarily correlated with the rate of bacterial killing.
为评估抗生素类别在革兰氏阴性菌所致脓毒症治疗期间内毒素释放率中的作用，我们从患有大肠杆菌所致脓毒症并接受氯霉素、庆大霉素或莫西沙星治疗的家兔身上采集了系列血样。测定了每份血样中活菌、游离内毒素和总内毒素的浓度。在用氯霉素治疗的家兔中，游离内毒素的几何平均水平与菌血症的几何平均水平保持成比例，这一结果表明不存在抗生素诱导的内毒素释放。相比之下，在用庆大霉素或莫西沙星治疗后，游离内毒素水平迅速升高，而菌血症水平下降，这一结果表明抗生素诱导了内毒素释放。尽管细菌杀灭率相似，但接受莫西沙星治疗的家兔中游离内毒素的平均水平比接受庆大霉素治疗的配对家兔高20倍（P小于0.05）。这些结果表明，革兰氏阴性菌所致脓毒症治疗期间的内毒素释放取决于所用抗生素的类别，且不一定与细菌杀灭率相关。
