Uppal Lipi, Singhi Sunit, Singhi Pratibha, Aggarwal Ritu
From the *Department of Pediatrics, and †Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Pediatr Infect Dis J. 2017 Jun;36(6):556-559. doi: 10.1097/INF.0000000000001513.
Treatment of acute bacterial meningitis in children with bactericidal antibiotics causes cell wall lysis and a surge in inflammatory cascade, which in turn contributes to neuronal damage and morbidity. Pretreatment with a nonbacteriolytic antibiotic, such as rifampin, has been shown to attenuate the inflammatory response in experimental models of bacterial meningitis. In a pilot study, in children with bacterial meningitis, we have studied markers of inflammatory response and neuronal damage in 2 groups of children with bacterial meningitis; one group received rifampin pretreatment with ceftriaxone and the other group received ceftriaxone alone.
Forty children with bacterial meningitis, who were 3 months to 12 years of age, were randomly assigned to receive either a single dose rifampin (20 mg/kg) 30 minutes before ceftriaxone or ceftriaxone alone was given. The primary outcome variables were cerebrospinal fluid (CSF) concentrations of tumor necrosis factor alpha (TNFα), S100B and neuron-specific enolase on day 1 and day 5, and secondary outcome variables were the values of TNFα and interleukin 6 in serum on day 1 and day 5; hearing and neurologic sequelae at 3 months after recovery from the illness.
Children in rifampin pretreatment group had significantly lower CSF TNFα concentrations [median (interquartile range [IQR]): 15.5 (7.2-22.0) vs. 53.0 (9.0-87.5) pg/mL, P = 0.019] and S100B [median (IQR): 145.0 (54.7-450.0) vs. 447.5 (221.0-804.6) pg/mL, P = 0.033] on day 1 and S100B [median (IQR): 109.7 (64.0-287.0) vs. 322 (106.7-578.0) pg/mL, P = 0.048] and neuron-specific enolase [median (IQR): 8.6 (5-14.75) vs. 18.2 (7.0-28.75) ng/mL, P = 0.035] on day 5 when compared with ceftriaxone alone group. The rifampin-treated group also had reduced morbidity and neurologic sequelae; however, these were not statistically significant.
Pretreatment with single dose rifampin 30 minutes before ceftriaxone administration reduced the CSF concentrations of markers of inflammation and neuronal damage in children with bacterial meningitis.
使用杀菌性抗生素治疗儿童急性细菌性脑膜炎会导致细胞壁溶解，并引发炎症级联反应激增，进而导致神经元损伤和发病。在细菌性脑膜炎的实验模型中，已证明用非杀菌性抗生素（如利福平）进行预处理可减轻炎症反应。在一项试点研究中，我们对两组细菌性脑膜炎患儿的炎症反应和神经元损伤标志物进行了研究；一组在使用头孢曲松前接受利福平预处理，另一组仅接受头孢曲松治疗。
40名年龄在3个月至12岁的细菌性脑膜炎患儿被随机分配，一组在头孢曲松给药前30分钟接受单剂量利福平（20mg/kg），另一组仅给予头孢曲松。主要结局变量为第1天和第5天脑脊液（CSF）中肿瘤坏死因子α（TNFα）、S100B和神经元特异性烯醇化酶的浓度，次要结局变量为第1天和第5天血清中TNFα和白细胞介素6的值；疾病恢复后3个月时的听力和神经后遗症。
与仅接受头孢曲松治疗的组相比，利福平预处理组患儿在第1天的脑脊液TNFα浓度显著降低[中位数（四分位间距[IQR]）：15.5（7.2 - 22.0） vs. 53.0（9.0 - 87.5）pg/mL，P = 0.019]以及S100B[中位数（IQR）：145.0（54.7 - 450.0） vs. 447.5（221.0 - 804.6）pg/mL，P = 0.033]，在第5天S100B[中位数（IQR）：109.7（64.0 - 287.0） vs. 322（106.7 - 578.0）pg/mL，P = 0.048]和神经元特异性烯醇化酶[中位数（IQR）：8.6（5 - 14.75） vs. 18.2（7.0 - 28.75）ng/mL，P = 0.035]也显著降低。利福平治疗组的发病率和神经后遗症也有所降低；然而，这些差异无统计学意义。
在头孢曲松给药前30分钟给予单剂量利福平预处理可降低细菌性脑膜炎患儿脑脊液中炎症和神经元损伤标志物的浓度。
