2013—2017单中心儿童B族链球菌脑膜炎临床分析

Clinical analysis of children with group B streptococcal meningitis in 2013-2017 in a single center

目的探讨B族链球菌(GBS)脑膜炎患儿的临床特点、死亡危险因素和细菌耐药性。方法回顾性收集2013年1月至2017年10月北京儿童医院住院的96例GBS脑膜炎患儿(男46例、女50例)的临床信息及菌株的耐药性检测结果。根据患儿起病年龄分为早发型(0~6日龄)、晚发型(7~89日龄)和超晚发型(90日龄~16岁),进行临床特点分析。根据头颅影像学结果分为有神经系统并发症组和无神经系统并发症组,分析其危险因素。根据出院后28 d结局分为死亡组和存活组,通过多因素Logistic回归分析死亡危险因素。组间比较应用χ^2检验、精确四格表法或非参数检验。结果96例GBS脑膜炎患儿中早发型18例(19%),晚发型71例(74%),超晚发型7例(7%),3组发病年龄分别为2(0~6)d、31(7~81)d、153(95~214)d。6例患儿发病前母亲有乳腺炎,6例胎膜早破。GBS脑膜炎患儿常见的临床表现有发热(91例,95%)、纳差(62例,65%)、抽搐(54例,56%)和意识改变(35例,36%)。早发型组、晚发型组和超晚发型组患儿在性别、入住重症监护病房比例和首次外周血白细胞水平方面差异均有统计学意义[13/18比28/71比5/7,5/18比31/71比0,12(4,18)×10^9/L比6(3,11)×10^9/L比13(6,17)×109/L,χ^2=7.705、6.065,H=9.885,P=0.024、0.042、0.007]。94例患儿进行头颅影像学检查,其中出现神经系统并发症60例(64%),最常见的为硬膜下积液或积脓31例(33%),其次为颅内出血26例(28%)、脑软化19例(20%)、脑萎缩15例(16%)、脑室管膜炎8例(9%)、脑积水4例(4%)。单因素分析显示抽搐为患儿神经系统并发症的危险因素[(63%(38/60)比41%(14/34),χ^2=4.310,P=0.038]。出院后28 d内死亡8例,病死率8%。多因素Logistic回归分析显示感染性休克(OR:9.548,95%CI 1.439~63.356, P=0.019)和呼吸衰竭(OR: 7.053,95%CI 1.160~42.888, P=0.034)是患儿死亡的独立危险因素。菌株对青霉素(68/68)、头孢曲松(47/47)、头孢吡肟(50/50)、万古霉素(60/60)、利奈唑胺(54/54)均100%敏感,对四环素、左氧氟沙星、克林霉素和红霉素的耐药率分别为5/12、17/45、38/46和32/37。结论儿童GBS脑膜炎以晚发型为主,神经系统并发症发生率高;感染性休克和呼吸衰竭是死亡的独立危险因素。GBS菌株对克林霉素和红霉素耐药严重。

Objective To explore the clinical features, the risk factors of mortality and drug resistance of the isolates in patients with group B streptococcus (GBS) meningitis. Methods A retrospective analysis was performed in 96 children with GBS meningitis (46 males and 50 females) at Beijing Children′s Hospital Affiliated to Capital Medical University from January 2013 to October 2017. The clinical characteristics, prognosis and drug resistance were reviewed and analyzed. According to the onset time, the patients were divided into early onset disease (EOD, 0-6 days), late onset disease (LOD, 7-89 days) and very late onset disease (VLOD, 90 days-16 years), the clinical features were compared. According to the results of cranial imaging examination, the patients were divided into two groups: those with neurological complications and those without neurological complications. The influencing factors of neurological complications were analyzed. According to the outcome of 28 days after discharge, patients were divided into death group and survival group. The risk factors of mortality were analyzed by multivariate Logistic regression analysis. Non-numeric variables were analyzed with χ^2 test or Fisher's exact test. Numeric variable between groups were compared with nonparametric test. Results A total of 96 patients were enrolled, including 18 (19%) EOD, 71 (74%) LOD and 7 (7%) VLOD cases. The median age of EOD cases was 2 days, with a range from 0 to 6 days. The median age of LOD cases was 31 days, with a range from 7 to 81 days. The median age of VLOD cases was 153 days, with a range from 95 to 214 days. Before the onset of the disease, the mother had mastitis in 6 cases and premature rupture of membranes in 6 cases. The common clinical manifestations of patients were fever (95%, 91/96), anorexia (65%, 62/96), seizure (56%, 54/96), and consciousness changes (36%, 35/96). The differences were statistically significant in gender (13/18 vs. 28/71 vs. 5/7,χ^2=7.705, P=0.024), the number of cases who was admitted to intensive care unit (ICU)(5/18 vs. 31/71 vs. 0,χ^2=6.065, P=0.042) and peripheral blood leukocyte (12(4, 18)×109/L vs. 6(3, 11)×10^9/L vs. 13(6, 17)×10^9/L, H=9.885, P=0.007) in EOD group, LOD group and VLOD group. Cranial imaging was performed in 94 patients, 60 patients (64%) developed neurological complications, including subdural effusion (31/94, 33%), followed by intracranial hemorrhage (26/94, 28%), cerebral softening (19/94, 20%), cerebral atrophy (15/94, 16%), ependinitis (8/94, 9%) and hydrocephalus (4/94, 4%). By univariate χ^2 test analysis, seizure (63%(38/60) vs.41%(14/34),χ^2=4.310, P=0.038) was a risk factor of neurological complications. Within 28 days after discharge, 88 patients survived and 8 patients died, with a fatality rate of 8%. The independent risk factors for the death were septic shock (OR: 9.548, 95% CI 1.439-63.356, P=0.019) and respiratory failure (OR: 7.053, 95% CI 1.160-42.888, P=0.034). All of isolates were susceptible to penicillin (68/68), ceftriaxone (47/47), cefepime (50/50), vancomycin (60/60) and linezolid (54/54), while the rates of resistance to tetracycline, levofloxacin, clindamycin and erythromycin were 5/12, 17/45, 38/46 and 32/37, respectively. Conclusions The main type of GBS meningitis is late onset cases. The incidence of neurological complications was high. The independent risk factors for death were septic shock and respiratory failure. The strains were severely resistant to clindamycin and erythromycin.