抗生素单一或联合用药诱导铜绿假单胞菌释放内毒素的比较性研究

目的 观察不同种类抗生素单独或联合应用对铜绿假单胞菌（Pseudomonas aeruginosa，Pa）释放内毒素（lipopolysaccharide，LPS）的影响，探讨其规律、特点及可能机制，为临床抗生素的合理选择提供参考。方法 选择临床上常用的6种抗生素：哌拉西林/他唑巴坦钠（PIP／TAZ），头孢哌酮（CPZ），亚胺培南/西司他丁钠（IPM／CIL），美罗培南（MEM），环丙沙星（CIP），阿米卡星（AMK），以0．5倍最小抑菌浓度（0．5mc）单一或联合体外作用于Pa，观察不同时相点抗生素的杀菌作用和细菌形态学改变，检测培养上清液中LPS水平。结果 6种抗生素单独应用时杀菌效应差异无统计学意义，联合用药组优于单一用药组。各种抗生素在引起细菌形态学改变的同时，诱导LPS释放程度不一。PIP／TAZ、CIP、MEM组作用后导致细菌成丝状变并伴随大量LPS释放，IMP／CIL组则引起细菌球状变，释放LPS相对较少。联合用药组及CPZ组大部分裂解，释放LPS明显减少。随作用时间延长，抗生素诱导LPS释放水平增加。结论 抗生素单独或联合体外作用于铜绿假单胞菌均可诱导LPS的释放，其释放水平与抗生素的种类、作用时间及细菌形态改变有关。临床抗感染治疗时在考虑抗菌效应同时应尽量选用低LPS诱导量的抗生素。

A comparative study on the release of endotoxin from Pseudomonas aeruginosa that is induced by single or combined antibiotic chemotherapy

Objective To observe the release of endotoxin from Pseudomonas aeruginosa after incubated with single or combined antibiotics and to explore possible mechanisms. Methods Cultures containing Pseudomonas aeruginosa were treated with six kinds of antibiotics as Piperacillin/Tazobactam (PIP/TAZ), Cefoperazone (CPZ), Imipenem/Cilastatin (IMP/CIL), Meropenem (MEM), Ciprofloxacin (CIP), Amikacin (AMK) single or combined in concentrations of 0.5 MIC. The changes of the CFU counting, morphology and the levels of endotoxin in the supernatants were observed at different time points. Results Different antibiotics induce endotoxin release from Pseudomonas aeruginosa during the change of morphological features and the killing of bacterial. All of the six kinds of single antibiotics could kill the bacterial with similar efficacy. A significant decrease in bacterial quantity and endotoxin release was noticed in combination of two antibiotics as compared to the single antibiotic groups. PIP/TAZ, MEM, CIP groups could convert the bacteria into filamentous shape with significant release of endotoxin, while IMP/CIL group could made the bacteria to spherical shape with less release of endotoxin as compared to the control. Antibiotics combined and CPZ group could induce lysis of bacteria with less LPS. Along with the prolongation of the action time, the endotoxin release increased. Conclusion All of the six kinds of antibiotics single or combined could induce Pseudomonas aeruginosa to release different amounts of endotoxin, which was correlated to the antibiotics classes, action time and the bacterial morphological changes. This result suggested an important strategy in antibiotic chemotherapy.