Nitsche D, Schulze C, Oesser S, Dalhoff A, Sack M
Surgical Research, University of Kiel, Germany.
Arch Surg. 1996 Feb;131(2):192-9. doi: 10.1001/archsurg.1996.01430140082022.
To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a rat model of intra- abdominal infection.
Immediately after intraperitoneal inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg), anesthetized Wistar rats were treated with a single intravenous dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6 mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg). An untreated control group received 0.9% sodium chloride instead of antibiotic. Plasma endotoxin activity, blood bacteria count, and mean arterial pressure were monitored at 60-minute intervals for 5 hours. At the end of the experiment, lavage was performed to determine the bacteria count in the peritoneal cavity.
In the untreated group, the blood bacteria count increased rapidly. Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was higher by a factor of 3.6 than in the untreated group. Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, and 38% lower in the gentamicin group. The lowest endotoxin levels were in the high-dose ciprofloxacin group. Bacteria counts in the peritoneal cavity were lowest in the gentamicin and high-dose ciprofloxacin groups. Except in the high-dose ciprofloxacin group, the endotoxin increase in the therapy groups was associated with a significant (P < .05) decrease in mean arterial pressure.
In the early phase of therapy, antibiotic-induced endotoxin release is influenced by the mode of action of the agent class. This is not the sole influence in every class. With quinolones, this effect is also influenced considerably by dosage, ie, by pharmacodynamics.
在大鼠腹腔感染模型中，研究不同种类和剂量的抗生素对革兰氏阴性菌感染中内毒素释放的影响。
在腹腔接种大肠杆菌（5×10⁷ 菌落形成单位/千克）后，立即对麻醉的Wistar大鼠静脉注射单剂量抗菌药物进行治疗：头孢噻肟（40毫克/千克）、环丙沙星（3毫克/千克或6毫克/千克）、亚胺培南（7毫克/千克或14毫克/千克）或庆大霉素（5毫克/千克）。未治疗的对照组接受0.9%氯化钠而非抗生素。每隔60分钟监测血浆内毒素活性、血细菌计数和平均动脉压，持续5小时。实验结束时，进行灌洗以确定腹腔内细菌计数。
在未治疗组中，血细菌计数迅速增加。治疗5小时后，头孢噻肟组的血浆内毒素活性比未治疗组高3.6倍。与头孢噻肟组相比，环丙沙星（3毫克/千克）组的内毒素活性低约26%，亚胺培南组低35%，庆大霉素组低38%。内毒素水平最低的是高剂量环丙沙星组。庆大霉素组和高剂量环丙沙星组的腹腔内细菌计数最低。除高剂量环丙沙星组外，治疗组内毒素增加与平均动脉压显著降低（P < 0.05）相关。
在治疗早期，抗生素诱导的内毒素释放受药物种类作用方式的影响。但并非每个种类都仅受此影响。对于喹诺酮类药物，这种影响还受剂量即药效学的显著影响。
