Dexamethasone as an adjunctive treatment of bacterial meningitis

This study was conducted on 77 Libyan infants and children aged month to 10 years with acute bacterial meningitis. Upon admission, the patients were divided randomly in two groups. Group I (38 patients) received ceftriaxone plus dexamethasone I.V. Group II (39 patients) received ceftriaxone alone. Both groups were compared for mean changes in CSF sugar, CSF protein and CSF polymorph count at 4th day of treatment. There was a significant difference between the two groups in CSF sugar and protein changes (P < 0.05) but not in CSF polymorph (P > 0.05). Both groups showed prompt clinical response and similar occurrence of acute complications, fatality rate and permanent neurological sequelae. However, group I manifested shorter duration of fever (P < 0.05). Dexamethasone improved the inflammatory reaction in acute bacterial meningitis and shortened the duration of fever but it did not have any significant effect on the fatality and the occurrence of neurological sequelae of this disease.     

Lack of effectiveness of dexamethasone in neonatal bacterial meningitis

A clinical trial was conducted to determine whether dexamethasone as adjunctive therapy alters the outcome of bacterial meningitis in neonates. Fifty-two full-term neonates with bacterial meningitis were enrolled in a prospective study. Infants were alternately assigned to receive either dexamethasone or not. Twenty-seven received dexamethasone in addition to standard antibiotic treatment and 25 received antibiotics alone. Dexamethasone therapy was started 10–15 min before the first dose of antibiotics in a dose of 0.15 mg/kg per 6 h for 4 days. Baseline characteristics, clinical and laboratory features in the two groups were virtually similar. Both groups showed a similar clinical response and similar frequency of mortality and sequelae. Six (22%) babies in the treatment group died compared to 7 (28%) in the control group (P = 0.87). At follow up examinations up to the age of 2 years, 6 (30%) of dexamethasone recipients and 7 (39%) of the control group had mild or moderate/severe neurological sequelae. Audiological sequelae were seen in two neonates in the dexamethasone group compared to one in the control group. Conclusion Adjunctive dexamethasone therapy does not improve the outcome of neonatal bacterial meningitis. Received: 22 December 1997 / Accepted: 14 March 1998     

Controversies in the management of bacterial meningitis

Bacterial meningitis is an important infection of childhood with significant morbidity and mortality, and clinicians are faced with controversies over steroid use and fluid restriction in its initial management because the standard of practice is not clear. A 1999 survey of paediatric infectious diseases specialists demonstrated that only 56% of respondents recommended dexamethasone for Haemophilus influenzae type b meningitis and only 34% recommended dexamethasone for Streptococcus pneumoniae meningitis, despite recommendations for dexamethasone in the 1997 Red Book. The present article illustrates a typical case presentation of bacterial meningitis, and discusses dexamethasone use and fluid restriction. The use of intravenous fluid therapy is also reviewed, based on results from the single prospective randomized clinical trial in this area.     

病原菌明确的细菌性脑膜炎146例临床及病原学分析

目的 分析细菌性脑膜炎患儿临床表现和病原特点,为临床诊治提供帮助。方法 收集复旦大学附属儿科医院2001年1月至2012年12月病原菌诊断明确的细菌性脑膜炎住院患儿,采集临床表现、辅助检查、并发症、病原菌种类和耐药情况等资料,分为0~28 d（新生儿组）,~1岁、~3岁和>3岁组进行描述分析。结果 146例细菌性脑膜炎患儿进入分析,新生儿组58例,~1岁组36例,~3岁组20例,>3岁组32例。①新生儿组发热、呕吐和脑膜刺激征的发生率较低,>3岁组伴有颅面、脊柱解剖畸形50%（16/32）。②革兰阳性菌占54.8%（80株）,以凝固酶阴性葡萄球菌（33株）、肠球菌（19株）和肺炎链球菌（12株）为主;革兰阴性菌占45.2%（66株）,以大肠埃希菌（30株）和鲍氏不动杆菌（10株）为主。③革兰阳性菌对万古霉素和利奈唑胺均敏感,革兰阴性菌除3/10株鲍氏不动杆菌和1/3株铜绿假单胞菌对美罗培南耐药外,余均敏感;大肠埃希菌、克雷伯菌和阴沟肠杆菌产超广谱β内酰胺酶阳性率分别达到66.7%、60.0%和100%。④63例（43.2%）出现急性期并发症,以硬膜下积液（26例）、脑积水（20例）和局部神经损害（13例）最常见;出现并发症主要病原菌为大肠埃希菌(15/30)、凝固酶阴性葡萄球菌（14/33）、肺炎链球菌（6/12）和鲍氏不动杆菌(6/10)。⑤出院结局：死亡或放弃治疗31例（21.2%）,其中肺炎链球菌性脑膜炎为5/12例（41.7%）。结论 细菌性脑膜炎新生儿临床表现多不典型,>3岁患儿应关注神经系统相关解剖结构缺陷的可能。可根据病原菌分布特点和药敏结果选用敏感抗生素。肺炎链球菌性脑膜炎患儿预后可能不良。     

Interleukin-8 levels in children with bacterial,tuberculous and aseptic meningitis

Objective : Interleukin-8 (IL-8) is produced in monocytes and vascular endothelial cells in response to stimulation with bacteria or lipopolysaccharides, and is released from these cells into blood stream or tissue fluid.Methods Cerebrospinal fluid (CSF) levels of interleukin-8 in 56 children with nonbacterial, bacterial and tuberculous meningitis (TBM), and in 15 control subjects were analyzed to evaluate the involvement of this cytokine in the pathogenesis acute bacterial meningitis and their discriminative value between different etiologies of meningitis. The kinetics of IL-8 concentrations during the course of bacterial meningitis was also evaluated in patients. IL-8 levels were significantly higher in bacterial and TBM than in aseptic meningitis and in control subjects (p<0.0001).Results: There was no difference in the levels of IL-8 between the non-bacterial meningitis and control groups. The analysis of the kinetics of production of IL-8 in patients with bacterial meningitis showed that the SSF concentrations of this cytokine decreased to undetectable values in recovery stage. Conversely in patients with TBM the concentrations of IL-8 were elevated in two weeks after beginning the specific treatment.Conclusion : The results suggest that determining IL-8 levels may be useful in the differential diagnosis.     

新生儿细菌性脑膜炎的诊治及观点更新

新生儿细菌性脑膜炎起病隐匿,临床症状不典型,病死率高,存活者可能会遗留神经系统并发症,因此及早诊断,规范治疗非常重要.2016年欧洲临床微生物与感染疾病协会(European Society for Clinical Microbiology and Infectious Diseases)发布了急性细菌性脑膜炎的诊治指南.本文结合该指南及最新文献,对新生儿细菌性脑膜炎的诊治进行了详述.     

Dexamethasone treatment for bacterial meningitis in children and adults

Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.     

Beta-glucuronidase in the diagnosis of bacterial meningitis and response to treatment

Aim: β-Glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the β-glucuronidase activity in the cell-free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. Methods: The β-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow-up lumbar punctures. Results: The β-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 μmoles 4-methylumbelliferone l ^-1  h ^-1 (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow-up punctures showed that the β-glucuronidase activity was the best prognostic index.

Conclusion: β-Glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.     

Bacterial meningitis: Mechanisms of disease and therapy

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines againstStreptococcus pneumoniae andNeisseria meningitidis will be the most promising development in the next decade.     

Prolonged and secondary fever in childhood bacterial meningitis

In order to study the causes of prolonged and secondary fever in bacterial meningitis, a group of 102 infants and children with proven bacterial meningitis were studied. The causative agent wasHaemophilus influenzae in 58% of patients,Streptococcus pneumoniae in 25% andNeisseria meningitidis in 17%. Prolonged fever was observed in 12% of the patients. The established causes include, in order of frequency, subdural effusion, drug fever, otitis media, gastroenteritis and urinary tract infection. Secondary fever was noted in 18% of the patients. The causes, in order of frequency, were urinary tract infection, subdural effusion, otitis media, phlebitis, pneumonia and drug fever. Neither relapse of the meningitis nor inadequate response to antibiotic therapy was the cause for prolonged or secondary fever. Neurological sequalae were observed in 21 patients. There was no correlation between prolonged or secondary fever and neurological sequalae. We conclude that prolonged and secondary fever in patients with treated bacterial meningitis is rarely caused by the primary infection.     

Latex agglutination test: An adjunct to the laboratory diagnosis of pyogenic bacterial meningitis

Gram stain, culture and latex agglutination test (LAT) of cerebrospinal flud were performed in 50 patients clinically diagnosed as suffering from pyogenic bacterial meningitus. Using all the three techniques, an aetiological diagnosis was made in 27 (54%).Neisseria meningitidis, Streptococcus pneumoniae and H. influenzae were the infecting organisms in 21 cases (44%). There were 12 additional cases in which LAT was the only clue to the diagnosis as compared to conventional techniques.Propionibacterium acnes was isolated from one case of anaerobic meningitis. It is concluded that LAT is an adjunct to conventional techniques in the diagnosis of pyogenic bacterial meningitis, where the latter tests fail.     

儿童表皮葡萄球菌脑膜炎脑脊液蛋白质组学的初步研究

目的：细菌性脑膜炎是致残、致死率较高的儿童时期常见中枢神经系统感染性疾病，其预后与诊断时间的早晚、是否及时治疗密切相关。而目前脑脊液(cerebrospinal fluid，CSF)中细菌培养的阳性率较低，使其确诊困难。该实验拟通过建立正常中国儿童CSF蛋白质双向凝胶电泳图谱，筛选表皮葡萄球菌脑膜炎(Staphylococcus epidermidis meningitis，SeM)特异性蛋白，为SeM的早期诊断提供线索，同时也为进一步治疗提供靶参考。方法：收集SeM患儿和同年龄正常儿童CSF各4 mL，固相pH梯度二维聚丙烯酰胺凝胶电泳（2-DE）技术分离蛋白质，以正常儿童CSF的2-DE凝胶为参考胶，将SeM患儿CSF的凝胶与之进行比较分析，寻找两组患儿CSF蛋白质谱的异常变化斑点。结果：正常儿童CSF分离获得蛋白质斑点438个，SeM患儿CSF分离获得蛋白质斑点425个，其中发现有25个蛋白质点仅在正常CSF表达，在SeM CSF中表达而在正常CSF中无表达的蛋白质点为12个；与正常CSF蛋白质点表达量比较，SeM有6个蛋白质点表达量有2倍以上上调，而19个蛋白质点表达量有2倍以上下调。结论：该实验成功建立了正常儿童和SeM患儿CSF蛋白质2-DE图谱，通过凝胶图像分析和计算机信息处理，发现了一些与SeM相关的蛋白质差异位点。对这些差异位点的进一步分析和鉴定，可能有助于发现与SeM相关的疾病特异性蛋白，为早期诊断及寻找新的药物靶点提供了新的思路。     

Passive exposure to tobacco smoke and bacterial meningitis in children

OBJECTIVE: To determine whether an association exists between passive exposure to tobacco smoke and bacterial meningitis in childhood, in an Australian population. METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of 71 children admitted to the Women's and Children's Hospital, North Adelaide, with bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of Haemophilus influenzae type b (Hib) meningitis decreased significantly during the study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99, Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test; P < 0.001). Although comparable numbers of cases and controls came from smoking families (41% vs 45%), more cases came from bi-parental smoking households (17% vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases were more likely to live in households where parents smoked inside (27% vs 13%; OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had had meningitis were significantly more likely to have parents who smoked inside the house, than children who had not had meningitis (66% vs 28%, Fisher's exact test; P = 0.005). CONCLUSION: This study suggests there may be an association between high levels of passive exposure to tobacco smoke and bacterial meningitis in Australian children. A study with larger numbers of affected children which quantifies passive exposure to tobacco smoke is needed to determine the strength of this association.     

No structural cerebral differences between children with a history of bacterial meningitis and healthy siblings

Abstract Aim: After bacterial meningitis, about one-third of children develops academic and/or behavioural limitations. The aim of our study was to search for structural differences in the brain, with a special focus on the hippocampus, between childhood survivors of bacterial meningitis with and without academic and/or behavioural limitations and healthy siblings. Patients and methods: A selection of a cohort, compiled in an earlier performed retrospective study, was used in this case-control study. Magnetic Resonance Imaging scans of the brain were performed in 43 post-meningitis children, of whom 18 had learning and/or behavioural limitations and 25 had no problems, and 18 controls. Voxel-based morphometry investigated the brain for structural changes. Hippocampal volume and lateral ventricle width were measured. Results: No structural differences between the groups, in any area of the brain, were found. There were no significant differences in hippocampal volume or lateral ventricle width. The group with limitations had three children with a right hippocampal volume smaller than two standard deviations below the mean of the control group. Conclusion: Despite hippocampus lesions found in experimental studies, we found no anatomical differences of the brain or hippocampus related to bacterial meningitis in children, nor to the academic and/or behavioural limitations seen after bacterial meningitis.     

儿童细菌性脑膜炎病原学及耐药性分析

目的了解广州地区儿童细菌性脑膜炎的病原菌分布特点及其耐药状况,为临床进行及时有效治疗提供实验室依据。方法回顾分析2005年1月—2009年12月广州妇女儿童医疗中心细菌性脑膜炎病例的脑脊液病原菌分离培养结果及其药敏试验情况。结果 5年来共从细菌性脑膜炎患儿的脑脊液标本中检出病原菌335株,其中革兰阳性菌215株(64.18%),革兰阴性菌109株(32.54%),真菌11株(3.28%)。主要是凝固酶阴性葡萄球菌(115株,占34.33%)和肺炎链球菌(81株,占24.18%)。新生儿及婴儿早期的病原菌主要是凝固酶阴性葡萄球菌。耐甲氧西林凝固酶阴性葡萄球菌发生率达55.65%。葡萄球菌对青霉素、红霉素、克林霉素耐药率超过70%,对万古霉素和利奈唑烷敏感;肺炎链球菌对青霉素耐药率为8.64%,对红霉素和克林霉素耐药率较高(>60%);革兰阴性杆菌对亚胺培南、头孢哌酮/舒巴坦及阿米卡星敏感率较高,但大肠埃希菌和肺炎克雷伯菌超广谱β内酰胺酶发生率为22.86%和27.59%。结论儿童细菌性脑膜炎主要病原菌是凝固酶阴性葡萄球菌和肺炎链球菌,早期准确的病原学诊断和及时采用敏感的抗菌药物治疗是降低后遗症发生率和病死率的重...     

The use of antibiotics in the treatment and prevention of infection in HIV-infected children

Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities. Selection of initial antibiotic therapy must be individualized in these children. Patients with community-acquired disease are most likely to have infection by polysaccharide-encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b. If it is possible to treat the patients at home, the use of amoxicillin-clavulanic acid might be appropriate. Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption. In hospitalized patients, concern for Gram-negative enteric pathogens other than polysaccharide-encapsulated organisms requires initial therapy with a third-generation cephalosporine in combination with an aminoglycoside. Trimethoprim-sulfamethizole is the most common drug used in HIV-infected children because it is recommended for the initial therapy and for prophylaxis of Pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.     

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。