耐药性结核性脑膜炎研究进展

结核性脑膜炎是由结核杆菌引起的中枢感染性疾病,是肺外结核病中最严重的一种,其多侵袭脑膜,有时可累及脑实质、脊髓,有很高的致死率。结核病在发展中国家中的感染趋势尤为突出。我国为人口大国,抗结核治疗和预防的形势异常严峻。随着抗结核药物的广泛使用,耐药性结核性脑膜炎患者数量增加,严重影响了结核性脑膜炎的预后。在耐药性结核性脑膜炎患者的治疗中,早期诊断、经验性治疗、调整治疗方案对患者的预后尤为重要。本文对耐药性结核性脑膜炎的分布、临床诊断、基因检测、治疗方案及预后进行系统性的总结。     

布氏杆菌脑膜炎病例报道2例及文献复习

目的:目前布氏杆菌性脑膜炎在国内只是偶见报道,本文报道2例布氏杆菌性脑膜炎,对其诊断及治疗进行探讨,并对布氏杆菌脑膜炎进行文献回顾.方法:我们近期连续通过检查脑脊液内布氏杆菌抗体的办法诊断了2例布氏杆菌性脑膜炎,并通过给予四环素、利福霉素及链霉素治疗1个月并通过随访.结果:半年后脑脊液内布氏杆菌抗体恢复阴性,临床症状完全消失.结论:通过我们的观察应用上述3联药物综合治疗1月对布氏杆菌性脑膜炎是有效的.     

伏立康唑联合小剂量糖皮质激素治疗儿童隐球菌性脑膜炎:2例报道并文献复习

目的探讨伏立康唑联合小剂量糖皮质激素对儿童隐球菌性脑膜炎的疗效。方法分析2例采用伏立康唑联合小剂量糖皮质激素治疗的儿童隐球菌性脑膜炎病例并进行相关文献复习。结果患儿经治疗后头痛等症状消失,颅内压逐渐下降至正常水平,脑脊液蛋白水平明显下降并稳定。结论伏立康唑联合小剂量糖皮质激素能迅速有效地控制临床症状,使用方便、副作用小,可作为儿童隐球菌性脑膜炎诱导治疗的一种选择。     

Two Cases of Cryptococcal Meningitis,one Treated with 5-Fluorocytosine

Cryptococcal meningitis occurred in two patients in the North of England. One, an elderly woman who was ill for 12 months with an obscure indolent meningitis until use of steroid drugs resulted in an acute exacerbation during which cryptococci were isolated, was treated successfully with amphotericin B. The other, a student from New Guinea with subacute meningitis, could not tolerate amphotericin B but responded to two courses of oral treatment with 5-fluorocytosine 100–200 mg./kg./ day without any appreciable side-effects. Further trials of this drug in the treatment of cryptococcosis are recommended.     

Oxidant and antioxidant activities in childhood meningitis

Animal studies have provided substantial evidence for a key role of reactive oxygen species, nitric oxide and its related compounds in the complex pathophysiology of bacterial meningitis. However, there is little information on changes in the redox status in human meningitis. In the present study, we evaluated the redox status and oxidative stress in the central nervous system of children with meningitis. Oxidant and antioxidant activities were assessed from cerebrospinal fluid levels of acrolein-lysine adducts (a marker of lipid peroxidation), nitrite (a marker of nitric oxide production) and bilirubin derivatives (a marker of antioxidant activity of bilirubin). All these markers were several times higher in children during the early phase of bacterial meningitis compared with those of children without meningitis and patients with aseptic meningitis. In the bacterial meningitis group, the levels of bilirubin derivatives correlated significantly with those of acrolein-lysine adducts and nitrite. Acrolein-lysine adducts and nitrite decreased significantly as the patients started to respond to treatment but bilirubin derivatives remained elevated. In conclusion, our data indicate the enhancement of both oxidant and antioxidant activities in the central nervous system of children with early bacterial meningitis, but not in those with aseptic meningitis. Clinical and laboratory improvement may be associated with a decrease in oxidant activities in the central nervous system.     

Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis

AIMS: To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis. RESULTS: Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin-6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin-8 level. CONCLUSION: Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.     

Angiostrongylus cantonensis: efficacy of albendazole-dexamethasone co-therapy against infection-induced plasminogen activators and eosinophilic meningitis

Angiostrongyliasis is one of the common causes leading to eosinophilic meningitis. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) may play a role in the pathogenesis. Administration of steroid drugs has been reported to possibly relieve the symptoms of eosinophilic meningitis. This study evaluates the curative effects of albendazole-dexamethasone co-therapy on eosinophilic meningitis in BALB/c mice. Assay indicators for the therapeutic effect include worm recovery, histopathological score of meningitis, tPA, uPA, total protein, and leukocyte counts. The results show that the albendazole-dexamethasone co-therapy significantly decreased (P<0.05) these factors after treatment on day 5 post-inoculation (PI), in contrast to treatment on 15 PI. Thus, the timing of medication is important and is closely related to the anthelmintic efficacy of a drug. At the same dosage and days post-infection, the earlier administration shows better results. This study showed that albendazole-dexamethasone co-therapy is an effective approach for the treatment of parasitic meningitis.     

结核性脑膜炎的诊断和治疗

结核性脑膜炎(TBM)是一种严重的肺外结核性,约占全部结核病的1%。TBM的死亡率和致残率高,至今仍是发展中国家最严重的疾病之一。儿童患者及合并HIV感染的结核性脑膜炎患者死亡率明显增高。结核性脑膜炎的具体发病机制仍不清楚,细菌和宿主的遗传因素在结脑的发病机制中发挥了至关重要的作用。尽管现代医学技术的进展,TBM的早期诊断仍存在困难。TBM的诊断依赖于临床表现、实验室检查以及影像学检查,脑脊液细菌涂片或培养找到结核分枝杆菌可确诊。早期诊断和治疗尤为关键。临床上往往从经验判断开始抗结核治疗。WHO指南推荐至少六个月的抗结核治疗。然而,部分指南推荐延长抗结核治疗至9-12个月。早期使用类固醇类激素可降低死亡率。抗结核药物耐药性与高死亡率相关。该综述描述了结脑的各个方面,重点强调结核性脑膜炎的早期诊断和治疗。     

Acetylcholinesterase activity in the rat brain after pneumococcal meningitis

Pneumococcal meningitis is a life-threatening disease characterized by acute purulent infection of the meninges causing neuronal injury, cortical necrosis and hippocampal apoptosis. Cholinergic neurons and their projections are extensively distributed throughout the central nervous system. The aim of this study was to assess acetylcholinesterase activity in the rat brain after pneumococcal meningitis. In the hippocampus, frontal cortex and cerebrospinal fluid, acetylcholinesterase activity was found to be increased at 6, 12, 24, 48 and 96 hr without antibiotic treatment, and at 48 and 96 hr with antibiotic treatment. Our data suggest that acetylcholinesterase activity could be related to neuronal damage induced by pneumococcal meningitis.     

LTA4H Genotype Is Associated with Susceptibility to Bacterial Meningitis but Is Not a Critical Determinant of Outcome

Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response is influenced by the patient’s LTA4H genotype. Despite less certain benefit, adjunctive dexamethasone is also frequently used in the treatment of pyogenic bacterial meningitis, but the influence of LTA4H genotype on outcomes has not been previously investigated. We genotyped the LTA4H promoter region SNP (rs17525495) in 390 bacterial meningitis patients and 751 population controls. rs17525495 was associated with susceptibility to bacteriologically confirmed bacterial meningitis (P = 0.01, OR 1.27 95% confidence interval [CI] 1.05–1.54) but did not influence clinical presentation, disease severity or survival following dexamethasone treatment.     

Bacterial meningitis after craniocerebral trauma in the community

Craniocerebral trauma is one of major risk factors for development of meningitis. We reviewed 30 cases of bacterial meningitis occurring in community after craniocerebral trauma. Alcohol abuse was significant risk factor occurring in trauma patients with meningitis present in 50% in our cohort (p=0.0001). The most common pathogen in posttraumatic meningitis was Str. pneumoniae (90% vs. 33.8%, p=0.0001). However mortality was very low, only 5% probably because of early diagnosis and treatment of patients at risk for bacterial meningitis but neurologic sequellea were significantly more common (p=0.00001) in patients after craniocerebral trauma.     

Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis

Angiostrongylus cantonensis can invade the central nervous system, leading to human eosinophilic meningitis or eosinophilic meningoencephalitis. Curcumin is a natural product which has the effects of anti-inflammation, anti-oxidation and anti-carcinogensis, while the administration of curcumin has been reported to possibly relieve the symptoms of meningitis. The present study tested the potential efficacy of curcumin in A. cantonensis-induced eosinophilic meningitis of BALB/c mice. Assay indicators for the therapeutic effect included the larvicidal effect, eosinophil counts and matrix metalloproteinase-9 (MMP-9) activity in angiostrongyliasis. Eosinophils were mildly reduced in treatment groups compared with infected-untreated mice. However, there were no significant differences in larvicidal effects or MMP-9 activity. This study suggests that anti-inflammatory treatment with curcumin alone has low efficacy, but the treatment does not interfere with MMP-9 expression and is not useful for larvicidal effects. The possible reasons include low curcumin across the blood-brain barrier and also those larvae that survive stimulate MMP-9 production, which promotes blood-brain barrier damage, with leukocytes then crossing the blood-brain barrier to cause meningitis. Further studies will be required to test these possibilities.     

IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis

The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequate antibiotic treatment. IL-1 is an important proinflammatory cytokine, which is up-regulated in brain tissue after the induction of meningitis. To determine the role of IL-1 in pneumococcal meningitis we induced meningitis by intranasal inoculation with 8 x 10(4) CFU of S. pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-1R(-/-)) mice and wild-type mice. Meningitis resulted in elevated IL-1alpha and IL-1beta mRNA and protein levels in the brain. The absence of an intact IL-1 signal was associated with a higher susceptibility to develop meningitis. Furthermore, the lack of IL-1 impaired bacterial clearance, as reflected by an increased number of CFU in cerebrospinal fluid of IL-1R(-/-) mice. The characteristic pleocytosis of meningitis was not significantly altered in IL-1R(-/-) mice, but meningitis was associated with lower brain levels of cytokines. The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis.     

腰椎置管治疗隐球菌性脑膜炎4例并文献复习

目的 观察早期腰椎置管引流加鞘内注射两性霉素B治疗伴有恶性高颅压隐球菌性脑膜炎的临床效果及探讨临床应用的可行性.方法 详细分析和归纳整理了我科应用腰椎置管法治疗的4例隐球菌性脑膜炎患者的临床资料.结果 4例患者经早期腰椎置管引流加鞘内注射两性霉素B治疗后临床症状迅速改善.经联合治疗后,痊愈3例,好转1例,4例患者随访至今均无复发.结论 早期腰椎置管引流加鞘内注射两性霉素B治疗隐球菌性脑膜炎能有效的降低隐球菌脑膜炎患者的高颅压,改善临床症状,提高疗效.     

Genetic variation in the β2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04-1.76; p?=?0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12-2.07; p?=?0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60-3.38; p?=?0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88-4.39]; p?=?0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts.     

BACTERIAL MENINGITIS AND OTHER DISEASES AFFECTING THE MENINGES—A Review of 349 Cases

Three hundred and forty-nine cases of disease affecting the meninges were observed at the San Bernardino County Charity Hospital in an eight year period.A total of 29 patients with meningococcal, H. influenzae and pneumococcal meningitis were treated. There were four deaths, of which three occurred during the first 24 hours in the hospital.Of 22 cases of unclassified meningitis, four probably were tuberculous, four probably were meningococcal and two probably were of virus origin.Under present treatment programs the differentiation between viral and bacterial meningitides is difficult and it is possible, therefore, that the reported incidence of the two groups may not represent the facts.Of 22 cases of unclassified meningitis, 12 had no specific characteristics which would permit a clinical diagnosis. One of the patients died.Of 70 cases of clinical meningitis, the infecting organism was identified in 69 per cent.Meningococcal meningitis made up only 17 per cent of 70 cases of purulent meningitis observed between July 1, 1945, and July 1, 1948.     

Trial of Chloramphenicol for Meningitis in Northern Savanna of Africa

In a controlled trial chloramphenicol proved as effective and much cheaper than penicillin for the treatment of group A meningococcal meningitis in Zaria, Nigeria. A short course of five days cured most patients. Adults and older children were soon able to take chloramphenicol by mouth, which reduced the cost and simplified treatment.It is suggested that chloramphenicol is a suitable alternative to sulphonamides for the treatment of meningococcal meningitis in those parts of Africa where the organism is sulphonamide-resistant.     

两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗隐球菌性脑膜炎的临床回顾性研究

目的 观察两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者的疗效和安全性,探讨非AIDS、非器官移植隐球菌性脑膜炎患者诱导治疗的新方案.方法 采用回顾性病例对照研究,18例非AIDS、非器官移植隐球菌性脑膜炎患者诱导期分别接受两性霉素B脂质体、氟胞嘧啶和伊曲康唑联合(研究组n=7)与两性霉素B、氟胞嘧啶和氟康唑联合治疗(对照组n=11).比较两组治疗方案在临床症状、体征变化、病死率、病原学转阴率、脑脊液改变等方面的差异及血常规、肝肾功能损害等不良反应发生情况.结果 治疗前研究组和对照组脑脊液新型隐球菌培养阳性分别为5例和8例(P =0.676),治疗1周后分别为5例和8例(P =0.676),治疗2周后分别为2例和4例(P =0.572),治疗3周后分别为0例和1例(P=0.611),治疗4周后,无死亡病例,两组脑脊液新型隐球菌培养均为阴性,脑脊液生化两组之间差异无统计学意义,对照组较研究组丙氨酸氨基转移酶(156.82±41.30 vs 97.00±22.02,P=0.003)、尿素氮(8.45±3.18 vs 5.54±1.28,P=0.020)升高更明显.结论 两性霉素B脂质体、氟胞嘧啶及伊曲康唑联合治疗非AIDS、非器官移植隐球菌性脑膜炎患者疗效确切,安全性较好,可以作为诱导期治疗的选择.     

Bacterial meningitis and other diseases affecting the meninges; a review of 349 cases

Three hundred and forty-nine cases of disease affecting the meninges were observed at the San Bernardino County Charity Hospital in an eight year period.A total of 29 patients with meningococcal, H. influenzae and pneumococcal meningitis were treated. There were four deaths, of which three occurred during the first 24 hours in the hospital. Of 22 cases of unclassified meningitis, four probably were tuberculous, four probably were meningococcal and two probably were of virus origin. Under present treatment programs the differentiation between viral and bacterial meningitides is difficult and it is possible, therefore, that the reported incidence of the two groups may not represent the facts. Of 22 cases of unclassified meningitis, 12 had no specific characteristics which would permit a clinical diagnosis. One of the patients died. Of 70 cases of clinical meningitis, the infecting organism was identified in 69 per cent. Meningococcal meningitis made up only 17 per cent of 70 cases of purulent meningitis observed between July 1, 1945, and July 1, 1948.     

THE DIAGNOSIS AND TREATMENT OF MENINGITIS

Treatment of meningitis is no longer a question of the administration of antimeningococcal serum and awaiting results. Today there is at hand an ever expanding armamentarium of drugs effective on various bacteria, rickettsia and some of the larger viruses. The skillful use of these singly or in combination offers an excellent prognosis in most forms of bacterial meningitis. Tuberculous meningitis continues to present a poor outlook, but this has been improved with more intensive therapy. More effective agents are needed in the treatment of this disease.“Shotgun” therapy may be indicated in critically ill patients prior to accurate bacteriological diagnosis; it is more important that therapy should include an effective agent or combination of agents than to attempt to determine in advance the most potent form of specific therapy. Partially treated purulent meningitis may be confused with aseptic meningitis. There is at present no effective therapeutic agent for the viral meningitides, but the prognosis is favorable in most of these diseases without specific therapy.