Introduction

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC), combined with imipenem or ceftazidime, in murine models of peritoneal sepsis (PS) and pneumonia induced by Pseudomonas aeruginosa.

Methods

The imipenem and ceftazidime-susceptible strain (Pa39) and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. The therapeutic efficacy and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia induced by Pa39 and Pa238 and treated with LPC, imipenem or ceftazidime, alone or in combination.

Results

In the PS model, LPC+ceftazidime reduced spleen and lung Pa238 concentrations (−3.45 and −3.56 log₁₀ CFU/g; P < 0.05) to a greater extent than ceftazidime monotherapy, while LPC + imipenem maintained the imipenem efficacy (−1.66 and −1.45 log₁₀ CFU/g; P > 0.05). In the pneumonia model, LPC + ceftazidime or LPC + imipenem reduced the lung Pa238 concentrations (−2.37 log₁₀ CFU/g, P = 0.1, or −1.35 log₁₀ CFU/g, P = 0.75). For Pa39, no statistically significant difference was observed in the PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC + imipenem and LPC+ceftazidime significantly decreased and increased the TNF-α and IL-10 levels, respectively, in comparison with the untreated controls and monotherapies.

Conclusions

These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections induced by ceftazidime-resistant P. aeruginosa.

中文翻译：

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溶血磷脂酰胆碱改变免疫反应对铜绿假单胞菌腹膜脓毒症和肺炎实验模型抗生素治疗效果的影响：联合治疗中LPC的治疗效果

 介绍

免疫反应刺激可能是抗菌治疗的辅助剂。在这里，我们评估了溶血磷脂酰胆碱（LPC）联合亚胺培南或头孢他啶对铜绿假单胞菌诱导的腹膜脓毒症（PS）和肺炎小鼠模型中免疫反应改变的影响。

 方法

使用亚胺培南和头孢他啶敏感菌株(Pa39)和亚胺培南和头孢他啶耐药菌株(Pa238)。测定了头孢他啶的药代动力学和药效学参数。在 Pa39 和 Pa238 诱导的 PS 和肺炎小鼠模型中测定治疗效果以及 TNF-α 和 IL-10 水平，并用 LPC、亚胺培南或头孢他啶单独或组合治疗。

 结果

在PS模型中，LPC+头孢他啶比头孢他啶单一疗法更大程度地降低了脾和肺Pa238浓度（-3.45和-3.56 log ₁₀ CFU/g； P < 0.05），而LPC+亚胺培南维持了亚胺培南疗效（-1.66和-1.66）。 −1.45 log ₁₀ CFU/g； P > 0.05)。在肺炎模型中，LPC + 头孢他啶或 LPC + 亚胺培南降低了肺 Pa238 浓度（-2.37 log ₁₀ CFU/g， P = 0.1，或 -1.35 log ₁₀ CFU/g， P = 0.75）。对于Pa39，联合治疗和单一治疗之间的PS和肺炎模型没有观察到统计学上的显着差异。此外，与未治疗的对照和单一疗法相比，LPC+亚胺培南和LPC+头孢他啶分别显着降低和升高TNF-α和IL-10水平。

 结论

这些结果证明了 LPC 加抗生素改变免疫反应对头孢他啶耐药铜绿假单胞菌引起的感染预后的影响。