新生儿细菌性脑膜炎预后不良的危险因素分析

目的 探讨新生儿细菌性脑膜炎预后不良的危险因素。方法 回顾性分析152例细菌性脑膜炎新生儿的临床资料,根据转归分为预后良好组（n=122）与预后不良组（n=30）,比较两组患儿的一般情况、首发症状及实验室检查结果,分析预后不良的危险因素。结果 预后不良组极低出生体重、外周血WBC < 5×10⁹/L或 > 20×10⁹/L、C-反应蛋白 > 50 mg/L、脑脊液WBC > 500×10⁶/L、脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L比例高于预后良好组（P < 0.05）,血培养和/或脑脊液培养阳性率、革兰阳性菌及无乳链球菌培养阳性率高于预后良好组（P < 0.05）。多因素logistic回归分析显示,脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L是新生儿细菌性脑膜炎预后不良的独立危险因素。结论 脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L是新生儿细菌性脑膜炎预后不良的危险因素。     

新生儿不同病原菌化脓性脑膜炎临床分析

目的探讨新生儿不同病原菌化脓性脑膜炎的临床特征。方法回顾性分析2011年1月1日至2012年12月31日172例新生儿化脓性脑膜炎患儿的临床资料。结果脑脊液外观浑浊和脓性54例(31.4%);脑脊液培养阳性70例(40.7%),以大肠埃希菌、葡萄球菌为主;并发症31例(18.0%),其中脑积水14例(8.1%)。大肠埃希菌脑膜炎组与其他病原菌组、不明病原菌组比较,脑脊液外观异常比例、脑脊液白细胞计数、脑脊液白细胞计数500×106/L比例、脑脊液糖和蛋白水平、发热持续时间、脑脊液恢复正常时间、住院时间和费用、并发症和死亡的比例差异有统计学意义(P均0.05)。结论对于脑脊液外观呈浑浊和脓性,尤其脑脊液白细胞数500×106/L时,需重点考虑大肠埃希菌感染可能,其并发症多、病死率高,预后相对较差。     

小儿化脓性脑膜炎临床和病因学分析

目的探讨化脓性脑膜炎的病因,为诊治提供科学依据。方法收集住院化脓性脑膜炎患儿371例,男252例,女119例;平均年龄(2.67±3.32)岁。对患儿临床表现及血液和脑脊液(CSF)相关参数进行分析。结果 371例中≤1岁患儿占46.36%,<3岁占80.59%,以发热(90.29%)、抽搐(52.56%)等症状就诊。82.21%患儿白细胞计数(WBC)>10×109/L,74.42%患儿中性粒细胞比率>50%,85.44%患儿脑脊液WBC≥500×106/L。血培养革兰染色阳性(GSP)37例,革兰阳性菌(GPB)24例,革兰阴性菌(GNB)13例。脑脊液培养阳性34例,GPB 19例,GNB 15例。脑脊液检测出肺炎链球菌8例,流感嗜血杆菌3例,奈瑟菌1例。死亡7例(1.88%)中,脑脊液2例GNB阳性,5例化脓性/混浊,4例蛋白>150 mg/dl和葡萄糖<1 mg/dl。结论化脓性脑膜炎的发病年龄多在婴幼儿阶段,临床表现多种多样,血液和脑脊液相关参数分析,能较好的提供病因诊断依据,并为临床治疗及预后提供参考。     

132例新生儿化脓性脑膜炎脑脊液分析

目的 探讨新生儿化脓性脑膜炎临床症状、脑脊液常规之间的关系及对预后的影响.方法 选取化脓性脑膜炎新生儿132例作为研究对象,根据脑脊液白细胞计数增高程度的不同,对比脑脊液蛋白和葡萄糖的定量,以及治疗后脑脊液细胞计数恢复正常的天数.结果 随着脑脊液白细胞计数的增高,脑脊液蛋白定量及白细胞计数恢复正常的天数差异有统计学意义(P＜0.05).结论 提高穿刺率有助于早期发现新生儿化脓性脑膜炎,脑脊液中蛋白定量对化脓性脑膜炎危重程度及预后的判定有一定意义,脑脊液白细胞计数增高的程度对疗程有影响.     

B群溶血性链球菌性脑膜炎8例临床分析

目的探讨B群溶血性链球菌(GBS)性脑膜炎的临床特点。方法选取2009—2012年广东省妇幼保健院新生儿重症监护病房收治的GBS脑膜炎病例,回顾性分析其围生期因素、临床表现、辅助检查、治疗和预后。结果研究期间共收治8例GBS脑膜炎患儿,发病日龄均>7天,主要表现为发热、抽搐、反应差,实验室检查炎症指标血白细胞(WBC)<4×109/L或>20×109/L 6例,超敏C反应蛋白(Hs-CRP)、降钙素原(PCT)等均不同程度增高,血小板变化不大,脑脊液呈典型化脓性脑膜炎改变,脑脊液培养GBS阳性8例,血培养GBS阳性4例,头颅CT证实脑积水4例。结论 GBS脑膜炎多为迟发性感染,临床表现与其他病原菌脑膜炎相似,脑脊液WBC明显增高,易复发,建议应用抗生素至少3周以上。     

大肠杆菌与肺炎链球菌所致儿童化脓性脑膜炎临床特点对比分析

目的 比较大肠杆菌与肺炎链球菌所致儿童化脓性脑膜炎 （简称化脑）的临床特征的差异,为临床病原学不明情况下化脑患儿抗生素的选择提供帮助。方法 回顾性比较分析大肠杆菌 （n=12）与肺炎链球菌 （n=15）所致化脑患儿的临床资料。结果 大肠杆菌组发病年龄39℃）及意识障碍发生率、首诊白细胞计数增高 （>12×109/L）的患儿比例显著低于肺炎链球菌组。两组间脑脊液常规及生化检查结果比较差异无统计学意义。大肠杆菌与肺炎链球菌对头孢类抗生素耐药率均较高,对氯霉素敏感率>90%;大肠杆菌对美罗培南100% 敏感,肺炎链球菌对万古霉素100% 敏感。结论 大肠杆菌与肺炎链球菌所致儿童化脑的临床特征存在差异。对于高热、意识障碍、血白细胞计数增高的化脑患儿可考虑肺炎链球菌感染;而年龄<3 个月,呈中低热、抽搐频繁、血白细胞计数<12×109/L的患儿可考虑大肠杆菌感染。     

儿童重症化脓性脑膜炎CD3＋ CD8＋ T细胞与炎症指标、体液免疫的变化

目的：通过观察儿童重症化脓性脑膜炎早期血CD3＋CD8＋T细胞的变化,以及与炎症指标、体液免疫指标之间的关系,探讨其在儿童重症化脓性脑膜炎发生发展中的临床意义。方法回顾性分析中国医科大学附属盛京医院PICU 2014年8月1日至2015年12月31日收治的39例1个月~14岁的重症化脓性脑膜炎患儿,血CD3＋CD8＋T细胞计数正常或升高(≥190个/mm3)为A组( n＝22),降低(<190个/mm3)为B组(n＝17),分析患儿的一般资料、血液炎症指标、体液免疫、脑脊液改变在两组患儿中的分布和差异。结果17例(43.6％)患儿CD3＋CD8＋T细胞明显下降;所有4例死亡均为B组患儿;虽然没有统计学差异,但 B 组 Glasgow 昏迷评分<8分者比例(58.8％)高于 A 组(31.8％)。B组C-反应蛋白、降钙素原中位数(最小值-最大值)分别为251.0(26.2-417.0)mg/L、32.7(0.9-100.0)ng/L,远远高于A组的106.5(12.0-458.0)mg/L、4.5(0.1-200.0)ng/L,差异有统计学意义(P<0.05);B组中6例(35.3％)外周血WBC<4×109/L,而 A组为1例(4.6％),中性粒细胞>80％的比例A组为7例(31.8％),而B组为12例(70.6％),两组比较差异有统计学意义(P<0.05)。 B组14例(82.3％)患儿脑脊液中糖含量<2.0 mmol/L,高于A组[11例(50.0％)],两组比较差异有统计学意义(P<0.05)。结论儿童重症化脓性脑膜炎CD3＋CD8＋T细胞可能受到抑制,其与患儿脑功能损伤程度、炎症反应以及预后相关。可能对指导临床免疫制剂的应用有一定帮助。     

细菌性脑膜炎早期并发症的预警因素

目的探讨细菌性脑膜炎早期并发症的预警因素。方法回顾分析2000~2005年本院75例细菌性脑膜炎患儿的临床资料及发生早期并发症的危险因素。结果细菌性脑膜炎患儿早期并发症的发生率为50.7%,以硬膜下积液和脑积水最为常见。早期并发症与发病年龄、是否伴昏迷、是否出现惊厥、脑脊液蛋白定量、脑脊液糖定量密切相关。其中,发病年龄≤12个月（OR=11.867,95%CI：2.592~54.33 P〈0.01）和脑脊液糖≤1.5 mmol/L（OR=14.088,95%CI：3.173~62.54 P〈0.01）是细菌性脑膜炎患儿发生早期并发症的危险因素。结论细菌性脑膜炎早期并发症的危险因素是发病年龄和脑脊液中糖的水平。     

力欣奇继续医学教育园地——思考病例系列(1)答案

(病例见本刊2012年第1期彩页)初步诊断:新生儿败血症,化脓性脑膜炎。应做的检查包括血常规、C-反应蛋白(CRP)、血常规、尿常规、粪常规、脑脊液检查、血培养、急诊生化、血糖、肝肾功能、TORCH(宫内感染全套)、X线胸片、头颅CT或磁共振等检查。检查结果:血常规示白细胞13.7×109/L,其中中     

足月儿与早产儿细菌性脑膜炎的临床分析

目的 探讨足月儿和早产儿细菌性脑膜炎的临床特征及转归特点。方法 回顾性分析102例新生儿细菌性脑膜炎患儿的临床资料,根据胎龄分为早产儿组（n=46）及足月儿组（n=56）,比较两组患儿临床表现、实验室结果、影像学结果及临床转归。结果 早产儿组临床表现主要为反应差和呼吸暂停/急促（P < 0.05）,足月儿组则以发热及抽搐多见（P < 0.05）。足月儿组脑脊液糖高于早产儿组（P < 0.05）,早产儿组C-反应蛋白、血培养阳性率及不良预后发生率高于足月儿组（P < 0.05）。两组外周血白细胞计数、脑脊液白细胞、脑脊液蛋白及脑脊液培养阳性率差异无统计学意义（P > 0.05）。结论 早产儿及足月儿细菌性脑膜炎临床表现有所不同,早产儿组不良预后发生率更高。     

Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial

A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinal fluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used.     

细菌性脑膜炎并脑积水的临床特点及危险因素

目的探讨细菌性脑膜炎并脑积水的临床特点,并分析其相关的危险因素,以降低其发生率,改善细菌性脑膜炎的预后。方法对2004年1月-2010年6月本院收治的111例细菌性脑膜炎患儿的临床资料进行回顾性分析。根据影像学结果,将患儿分为细菌性脑膜炎并脑积水组(n=16)及细菌性脑膜炎无脑积水组(n=95),应用SPSS 17.0软件对2组患儿的基本情况、临床表现、实验室结果及抗生素治疗情况等进行比较,对相关因素进行Logistic回归分析,筛选出脑积水发生的高危因素。结果细菌性脑膜炎并脑积水的发生率为14.4%(16/111例),以梗阻性脑积水为主(14/16例,87.5%),75%(12/16例)患儿脑积水出现在起病4周内,确诊时CT/MRI的检查次数为1～3次,2例患儿在起病后2个月行脑室-腹腔分流术,2例脑积水患儿死亡。2组临床资料比较显示年龄、发热>10 d、惊厥、意识障碍、经验性治疗失败、颅内低密度灶、低Hb水平、高脑脊液蛋白水平、低脑脊液葡萄糖水平均与脑积水发生有关(Pa<0.05),Logistic回归分析显示意识障碍、经验性治疗失败、低Hb水平是细菌性脑膜炎并脑积水的独立危险因素。结论脑积水是细菌性脑膜炎的一个严重并发症之一,临床表现及实验室检查结果可作为细菌性脑膜炎并脑积水的预测指标。     

Early prediction of neurological sequelae or death after bacterial meningitis

This study determined independent predictors of the occurrence of permanent neurological sequelae or death after childhood bacterial meningitis. Data were used from a large study on children (aged 1 mo to 15 y) initially presenting with meningeal irritation. A nested case-control study was performed on children with (n = 23) and without (n = 70) permanent neurological sequelae (hearing impairment, locomotor dysfunction, mental retardation or epilepsy) or death after bacterial meningitis. Predictors obtained from clinical evaluation and laboratory tests at presentation and during the clinical course were identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses. The study population comprised 23 cases and 70 controls (52% boys, median age 2.8 y). Independent predictors for an adverse outcome after bacterial meningitis were male gender, atypical convulsions in history, low body temperature at admission and the pathogen Streptococcus pneumoniae. The area under the ROC curve of this prediction rule was 0.87 (95% confidence interval: 0.78-0.96), which was not improved by adding other characteristics. A score including these independent predictors could classify patients into categories with increasing risk for an adverse outcome. Conclusion: Clinical characteristics available early in the clinical course, such as gender, atypical convulsions in history, low body temperature at admission and the pathogen, are predictive for the occurrence of permanent neurological sequelae or death after bacterial meningitis in childhood. The pathogen type, in particular, is the main prognostic determinant of childhood bacterial meningitis.     

磁共振形态学半定量评分对新生儿细菌性脑膜炎出院结局的评估价值

目的 分析MRI形态学半定量评分对新生儿细菌性脑膜炎出院结局的评估价值。方法 收集复旦大学附属儿科医院2011年7月至2013年12月NICU收治的出院诊断为新生儿细菌性脑膜炎的病例,采用基于大脑损伤MRI形态学分析的半定量评分,对头颅MRI图像进行回顾性分析。MRI形态学评价包括脑室扩大、脑室旁白质容积丢失、脑白质囊性病灶、内囊后肢髓鞘化异常、皮质信号异常、颅内脑外间隙异常、基底节信号异常、脑白质非囊性信号异常、脑室内出血、脑室积脓、脑膜异常强化、室管膜异常强化和脑脓肿。将上述13项评分归纳为脑白质异常（WMA）、脑灰质异常（GMA）和非脑实质异常（NPA）。同时采集患儿出生孕周、发病时间、MRI检查时间、发病至MRI检查间隔时间和出院结局。按照出生孕周分为早产儿组和足月儿组,再按照出院结局分为预后良好和预后不良亚组,在各组内比较亚组之间时间因素、MRI单项评分和综合评分的差异。结果 63例新生儿细菌性脑膜炎病例进入分析（早产儿组18例,足月儿组45例）。MRI单项评分构成预后良好和预后不良亚组间差异有统计学意义的指标：早产儿组中有脑室扩大(P=0.012)和脑室旁白质容积丢失(P=0.004);足月儿组有脑室扩大(P=0.002)、脑室旁容积丢失(P=0.040)、颅内脑外间隙异常(P=0.005)和脑室内出血(P=0.038)。MRI综合评分中,早产儿组WMA评分(P=0.001)和NPA评分（P=0.039）、足月儿组NPA评分(P=0.018)在预后不良和预后良好亚组之间分布差异有统计学意义。足月儿组和早产儿组内不同预后亚组的各时间因素差异未发现统计学意义或临床意义。结论 新生儿细菌性脑膜炎MRI脑室扩大和脑室旁白质容积丢失预示早产儿出院不良结局;脑室扩大、脑室旁白质容积丢失、颅内脑外间隙异常和脑室内出血预示足月儿出院不良结局。WMA评分高预示早产儿出院不良结局,NPA评分高预示早产儿和足月儿出院不良结局。     

儿童细菌性脑膜炎95例病原菌分布和预后分析

目的了解儿童细菌性脑膜炎(BM)病原菌分布、细菌耐药性、临床特征和预后。方法回顾分析2011年1月至2015年7月期间住院治疗的病原体明确的BM患儿的临床资料。按出院时结局将患儿分为结局良好和结局不良组。分析比较各组患儿的病原菌分布、细菌耐药性、临床特征及预后。结果共纳入95例病原体明确的BM患儿,其中69例(72.6%)为革兰阳性菌,以肺炎链球菌(43例,45.3%)占首位;26例为革兰阴性菌(27.4%),以大肠埃希菌(13例,13.7%)占首位。肺炎链球菌和大肠埃希菌对青霉素的耐药率均超过了50%。BM患儿神经系统并发症包括硬膜下积液、脑积水、脑实质损伤,以及听力和视力损伤等。多元logistic回归分析显示,意识障碍、昏迷、脑脊液葡萄糖水平低下是BM患儿出院时不良结局的独立危险因素。结论儿童BM的病原体以肺炎链球菌和大肠埃希菌为主,对青霉素的耐药率高。BM患儿可出现不同程度的神经系统后遗症,意识改变和异常以及脑脊液葡萄糖水平低下提示患儿出院时不良结局。     

Duration of symptoms and outcome in bacterial meningitis: an analysis of causation and the implications of a delay in diagnosis.

The prompt diagnosis and therapy of bacterial meningitis remain enduring clinical challenges, for no physician would knowingly delay appropriate therapy. However, whether a delay in the initiation of antimicrobials in fact causes a worse outcome is a separate and tangential question. In clinical medicine a treatment decision involves a bedside estimate of the risk and potential severity of illness balanced against the benefits and adverse effects of therapy. For severe infections, the inexorable damage of untreated disease is presumed, and antimicrobials properly are given without hesitation. In contrast the methodical weighing of evidence regarding the issue of causation is for the purpose of characterizing biologic phenomena. Although legal and medical implications may be contained in such an analysis, its relevance to any particular clinical case is only retrospective. To judge responsibly the strength of a causative link, all available scientific evidence must be analyzed by established criteria. Such as analysis suggests that any connection between a delay in the treatment of bacterial meningitis and outcome depends on the presenting clinical pattern. If the presentation is that of a nonspecific illness with general symptoms, then a short delay of < 3 to 5 days does not appear to alter the risk of sequelae or death. In the case of fulminant meningitis a delay in initiating therapy seems unconnected to outcome. Finally for patients with a history of clinically overt meningitis, an inappropriate delay in commencing therapy incrementally increases the risk of permanent injury.     

Clinical indicators for lumbar puncture

This study was conducted to demonstrate that experienced pediatricians using standard clinical indications for performing a lumbar puncture should have a higher yield of positive spinal taps than previously reported and also can detect bacterial meningitis. These indicators included temperature elevation, inability to be consoled, level of alertness, nuchal rigidity, bulging fontanel, decreased appetite, rash, referral, and febrile seizures. Eighty-two of 381 (22%) lumbar punctures were positive for pleocytosis and/or organisms. Patients were divided into two groups, consisting of those with one indicator (low risk) and those with greater than one indicator (high risk). Thirteen of 14 patients with bacterial meningitis were placed in the high risk group. The single patient in the low risk group had been pretreated with antibiotics. The positive predictive value in bacterial meningitis for a score greater than one was 5%. The average number of clinical indicators in bacterial meningitis was 3.7, versus 2.4 in viral meningitis and 1.6 without meningitis. These findings suggest that, in the absence of prior antibiotic therapy, an experienced pediatrician can clinically detect patients at high risk for bacterial meningitis. Nonbacterial meningitis cannot be as readily detected clinically.     

Risk factors for development of bacterial meningitis among children with occult bacteremia

To identify risk factors for the development of bacterial meningitis, we compared clinical characteristics in children with occult bacteremia who did and those who did not subsequently develop bacterial meningitis. The estimates of risk were adjusted for the possible confounding effects of other characteristics by using logistic regression. Of 310 children (median age 15 months) who had occult bacteremia with Streptococcus pneumoniae, Haemophilus influenzae type b, or Neisseria meningitidis at either Yale-New Haven Hospital or Children's Hospital of Pittsburgh, bacterial meningitis subsequently developed in 22 (7%). Compared with the risk associated with occult bacteremia with S. pneumoniae, the adjusted relative risk for bacterial meningitis was 85.6 (P less than 0.0001) and 12.0 (P = 0.0001) for N. meningitidis and H. influenzae type b, respectively. By contrast, the adjusted relative risk associated with a lumbar puncture at the initial visit was only 1.2 (P = 0.78). The development of bacterial meningitis in children with occult bacteremia is strongly associated with the species of bacteria that causes the infection, but not with a lumbar puncture or with other clinical characteristics identifiable at the initial visit.     

Randomized trial of four vs. seven days of ceftriaxone treatment for bacterial meningitis in children with rapid initial recovery

BACKGROUND: Seven days or more of antimicrobial treatment is the standard for bacterial meningitis, although third generation cephalosporins are usually able to sterilize cerebrospinal fluid within 24 h. The limited experience from shorter regimens in children is encouraging, and we hypothesized that in rapidly recovering patients older than 3 months of age it would pose no risk for adverse outcome. METHODS: Strict clinical and laboratory criteria were used to define rapid initial recovery, in which case ceftriaxone therapy was either stopped after 4 days (4 injections) in children born on even dates (N = 53) or continued for 7 days in patients born on odd dates (N = 47). Outcomes were compared on Day 7 of hospitalization and at 1 to 3 months after discharge. RESULTS: On Day 7 no differences (P > 0.05 for each criteria) were observed between the 4-day and the 7-day groups regarding fever, clinical signs or serum C-reactive protein concentration. At the follow-up visit 1 to 3 months after discharge the 4-day group had fewer sequelae than the 7-day group (0% vs. 5% neurologic sequelae, P = 0.39 and 3% vs. 9% hearing loss, P = 0.49, respectively). One child in the 4-day group who had fully recovered was subsequently readmitted 53 days after the first hospitalization with recurrent Haemophilus influenzae meningitis. CONCLUSIONS: Four days of ceftriaxone therapy proved to be a safe alternative in patients with rapid initial recovery from bacterial meningitis. A 4-day course of treatment is particularly beneficial for countries with limited resources.