氨苄西林和阿奇霉素联合治疗改善了B族链球菌败血症小鼠模型的预后。

Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis.

作者信息

Upadhyay Kirtikumar, Hiregoudar Basu, Meals Elizabeth, English Boyce Keith, Talati Ajay J

机构信息

Children's Foundation Research Center at Le Bonheur Children's Hospital; University of Tennessee Health Science Center, Memphis, TN, United States of America.

Division of Neonatal-Perinatal Medicine; University of Tennessee Health Science Center, Memphis, TN, United States of America.

出版信息

PLoS One. 2017 Jul 31;12(7):e0182023. doi: 10.1371/journal.pone.0182023. eCollection 2017.

BACKGROUND

Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation.

METHODS

TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end.

RESULTS

GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005).

CONCLUSIONS

Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

背景

有证据表明，链球菌感染的β-内酰胺单药治疗可能引发更强的炎症反应，且不如与大环内酯类药物联合治疗。我们推测，单独使用大环内酯类药物或与β-内酰胺类药物联合用于B族链球菌（GBS）败血症，可通过减轻炎症来改善预后。

方法

在四种治疗方案（单独使用氨苄西林、单独使用阿奇霉素或阿奇霉素加氨苄西林联合使用）存在的情况下，从用GBS分离株刺激的RAW 264.7细胞的上清液中测量肿瘤坏死因子-α（TNF-α）。建立GBS败血症小鼠模型，并用相同的四种方案进行治疗。监测临床败血症评分；最后测量血清细胞因子（TNF-α、白细胞介素-6、白细胞介素-10）和趋化因子（巨噬细胞炎性蛋白-1α）。

结果

与单独使用氨苄西林相比，暴露于阿奇霉素或联合用药（阿奇霉素加氨苄西林）的GBS分离株在体外刺激产生的TNF较少。在小鼠败血症模型中，联合治疗的小鼠死亡率较低，败血症评分也降低。与单独使用氨苄西林（260±160 pg/ml）相比，单独使用阿奇霉素（66±52 pg/ml）或氨苄西林加阿奇霉素联合使用（52±22 pg/ml）治疗的小鼠平均血清白细胞介素-6较低（p<0.005）。