Central Nervous System Bacterial Infections

中枢神经系统细菌感染
  • 文章类型: Clinical Trial Protocol
    中枢神经系统感染(CNSI)是神经外科手术后常见的并发症,预后较差。传统的微生物培养方法检测率低,耗时长。宏基因组下一代测序(mNGS)已显示出更快的优势,更准确,更全面的临床微生物学。先前的研究表明,mNGS在CNSI的诊断中具有很高的敏感性。mNGS在临床应用中是否具有卫生经济价值还有待研究。我们设计了一个潜在的,单中心,优势随机对照试验比较mNGS与使用决策树模型诊断CNSI的传统方法的成本-效果。总共204名患者将被招募并随机分配到mNGS组或传统方法组。两组患者根据不同的临床表现和检查结果进入不同的决策点。然后,他们将由专家小组在相应的决策点做出治疗决定。主要结果是增量成本效益比,这是回收率每提高1%所增加的成本。次要结果是时间成本的比较,检测成本,两组间与抗生素治疗相关的费用。IMPORTANCE诊断和治疗术后中枢神经系统感染(PCNSI)仍然具有挑战性,因为传统方法用于识别脑脊液中的微生物的低检出率和耗时的性质。宏基因组下一代测序(mNGS)技术通过快速测序和分析微生物基因组,可以快速全面地了解PCNSI中的微生物组成。本研究旨在评估在北京天坛医院神经外科术后患者中使用mNGS与传统细菌培养指导的PCNSI诊断和治疗的经济影响。mNGS是一个相对昂贵的测试项目,在诊断颅内感染的临床应用中是否具有相应的卫生经济意义还没有明确的研究。因此,研究者希望探讨mNGS检测在神经外科术后PCNSI中的临床应用价值。
    OBJECTIVE: Diagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.
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  • 文章类型: Journal Article
    中枢神经系统感染(CNSI)是一种重要的感染类型,困扰着神经病学和神经外科科学领域。在临床和实验室评估中,及时准确地诊断CNSI是一项重大挑战;然而,开发新的方法可能有助于改进诊断方案.本研究评估了第二代微/纳米流体芯片平台(MNCP-II),它克服了诊断CNS中细菌和真菌感染的困难。MNCP-II操作简单,并且可以在50分钟内鉴定出44个属或物种靶标和35个遗传抗性决定子。评价第二代微/纳米流控芯片平台在CNSI多中心研究中的诊断准确性。首先使用六种不同的微生物标准确定使用第二代微/纳米流体芯片平台的检测限(LOD)。使用MNCP-II平台评估了从微生物培养阴性的CNSI患者收集的总共180个含细菌/真菌的脑脊液(CSF)培养物和26个CSF样品,以鉴定微生物和遗传抗性决定因素。将结果与通过常规鉴定和抗菌敏感性测试方法获得的结果进行比较。发现用MNCP-II测试的各种微生物的LOD在DNA的250-500拷贝的范围内。对于180个CSF微生物阳性培养物,平台与常规鉴定方法的符合率为90.00%;8个物种达到100%的一致性。在9种抗生素抗性基因的检测中,包括碳青霉烯酶,ESBLs,氨基糖苷类,万古霉素相关基因,还有mecA,与常规抗菌药物敏感性试验方法的符合率超过80.00%。对于碳青霉烯酶和ESBLs相关基因,平台试验的敏感性和阳性预测值均较高(>90.0%),完全可以满足临床诊断的要求.MNCP-II是一个非常有效的分子检测平台,可以辅助CNSI的诊断,可以显着提高诊断效率。
    Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients with negative microbial cultures were evaluated using the MNCP-II platform for the identification of microorganism and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. The LOD of the various microbes tested with the MNCP-II was found to be in the range of 250-500 copies of DNA. For the 180 CSF microbe-positive cultures, the concordance rate between the platform and the conventional identification method was 90.00%; eight species attained 100% consistency. In the detection of 9 kinds of antibiotic resistance genes, including carbapenemases, ESBLs, aminoglycoside, vancomycin-related genes, and mecA, concordance rates with the conventional antimicrobial susceptibility testing methods exceeded 80.00%. For carbapenemases and ESBLs-related genes, both the sensitivity and positive predictive values of the platform tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. MNCP-II is a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.
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  • 文章类型: Journal Article
    Cutibacterium acnes has emerged as a significant cause of postoperative central nervous system infections (PCNSIs). We sought to determine risk factors and outcomes associated with C. acnes PCNSI.
    This was a single-center 1:1 case-control study of patients with monobacterial C. acnes-associated PCNSI (cases) and unmatched controls with PCNSI caused by aerobic organisms. Patient and procedure-related characteristics were compared between groups. The main outcome was cure at 90 days after diagnosis. Mortality and neurologic disability were secondary outcomes.
    We identified 13 patients with C. acnes PCNSI and 13 controls. All patients had postoperative intracranial abscess. Onset of infection was significantly later for cases versus controls (median and range, 22 [19-116] days and 15 [1-27] days, respectively; P = 0.002). Prolonged anaerobic incubation was required for C. acnes isolation (median, 8 days vs. 2 days for aerobic pathogens; P < 0.0001). The use of sealant and implants, fever at presentation, and white blood cell and C-reactive protein levels were similar between the 2 groups. All patients underwent surgical drainage. Patients received a median of 4 antibiotic drugs and 85 antibiotic days of treatment, with no significant between-group differences. Cure at 90 days was achieved for 10 patients (76.9%) with C. acnes PCNSI and 11 (84.6%) controls (P = 1.0).
    C. acnes PCNSI presents later than infection with aerobic bacteria but is associated with similar risk factors and clinical outcomes. These results underscore the importance of prolonged anaerobic incubation to optimize the recovery of C. acnes in the laboratory.
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  • 文章类型: Case Reports
    BACKGROUND: Melioidosis is a tropical disease caused by Burkholderia pseudomallei (B. pseudomallei). It can infect any organ system and lead to multiple abscesses. A few studies reported that central nervous system (CNS) is also involved. We present a diabetic patient with multi-systemic melioidosis that affected the CNS, thorax, and spleen. The aim was to study the clinical and radiological features of melioidosis and enhance understanding of the disease.
    METHODS: A 38-year-old male presented with cough and expectoration mixed with blood for several days. Chest computed tomography (CT) showed a patchy opacity in his left lung, and multiple low-density lesions in his spleen. After 10 days of antibiotics treatment, his clinical symptoms improved and he was discharged from the hospital. But 8 months later, the patient experienced sudden onset of left limb weakness and seizure and was re-admitted to the hospital. Brain CT indicated a low-density lesion over the right frontal lobe, and magnetic resonance imaging (MRI) indicated a well-enhanced lobulated lesion with multiple diffusion restriction areas in the lesion. He had a neuronavigation-guided open surgery but no malignancy was found. B. pseudomallei was cultured from the operative samples. After 4 months of systemic and intraventricular antibiotic administration treatment, he recovered complete consciousness with left hemiparesis.
    CONCLUSIONS: Multi-systemic melioidosis may present atypical clinical, neurological, and radiological manifestations. It is extremely important to accurately diagnose before treatment is selected. CNS melioidosis in early stage manifests similar symptoms to malignancy or stroke. It might mislead to a false diagnose. Diffusion weighted imaging (DWI) can help in differentiate abscesses from cystic tumours.
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  • 文章类型: Journal Article
    OBJECTIVE: The purpose of the study was to investigate the pharmacokinetics of combined intravenous (i.v.) and intracerebroventricular (i.c.v.) vancomycin for patients with intracranial infections after craniotomy and to provide the basis for establishing the intracranial local administration criterion.
    METHODS: Fourteen postoperative intracranial infection cases with surgical cavity/ventricular drainages were given vancomycin (1.0 g, i.v. drip for 2 hours, quaque 12 h, and a simultaneous i.c.v. injection of 10 mg). Their blood and cerebral spinal fluid (CSF) specimens were collected at each time point before and after administrations. The concentrations and biochemical properties were measured.
    RESULTS: The 1-hour serum vancomycin concentration reached a peak of 46.38 ± 33.39 mg/L; the trough concentration of 48 hours was 8.10 ± 7.11 mg/L; the CSF vancomycin concentration reached a peak of 382.17 ± 421.00 mg/L at 0.25 hours, and the 48-hour trough concentration was 30.82 ± 29.53 mg/L. The inhibitory quotient was calculated at 15.4 by the minimum inhibitory concentration 2 mg/L of target bacteria and had reached the range of 10 to 20 recommended by Infectious Diseases Society of America guidelines. The pH value and osmotic pressure of CSF were found to have no significant changes before and after administration. There was no increasement of seizures and ototoxicity in our study. Before the drug administration and 1 week later, the changes of creatine had no statistically significant, with P > .05.
    CONCLUSIONS: The combined i.v. and i.c.v. administration may improve CSF vancomycin concentrations without side effects at the same dosage. Our finding suggests that it can be an option for the treatment of severe intracranial infections after craniotomy; however, its safety and effectiveness need to be confirmed by further large-scale studies.
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  • 文章类型: Journal Article
    BACKGROUND: Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that Mycobacterium tuberculosis can actively interfere with the apoptosis of infected cells. In vivo studies have been performed in adult populations but have not focused on this process in children. In the present study, we analyzed spontaneous T lymphocyte (PBT) apoptosis in the peripheral blood of children with central nervous system tuberculosis (CNS TB), before and after chemotherapy, and compared the results with healthy controls.
    METHODS: A case-control study was conducted from January 2002 to June 2009. It included 18 children with CNS TB and 17 healthy controls. Spontaneous apoptosis of PBTs, including CD4+, CD8+ and CD8+/CD28+ T cells, was evaluated after 24 and 72 h of culture in complete medium, using the Annexin V detection test. Analysis was conducted before and after chemotherapy, and expression of the apoptotic markers CD95 (Fas) and Fas ligand (FasL) was evaluated.
    RESULTS: Higher percentages of apoptotic T cells and CD4 lymphocytes were isolated from children with acute phase CNS TB than from children in the control group (p < 0.05). This difference significantly decreased after 60 days of specific treatment. In children with CNS TB, high levels of Fas ligand expression were detected in lymphocyte populations, associated with a high percentage of Fas positive cells, before and after treatment. In contrast to the CD4+ apoptosis profile, we did not find any significant difference in total CD8+ cell apoptosis between children with acute phase disease and the control group. However, the percentage of apoptotic CD8+/CD28+ T cells was significantly higher in the children with acute phase disease than in the healthy controls.
    CONCLUSIONS: Our findings indicate that CNS TB in pediatric patients increases the sensitivity of CD4 and CD8+/CD28+ T cells to apoptosis, suggesting a hypoergic status of this infection. This could play a key role in the immunopathogenesis of this complicated form of TB. Interestingly, specific chemotherapy is able to normalize both apoptosis sensitivity and T-cell activation.
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  • 文章类型: Journal Article
    Spinal epidural abscess (SEA) is a rare, but serious, condition with multiple causes. We prospectively studied the aetiology, predisposing factors, and clinical outcomes of SEA in all patients with SEA treated in our hospital\'s neurosurgical service from 2004 to 2008. For each patient, we recorded the medical history, comorbidities, focus of infection, pathogen(s), and outcome. The 36 patients (19 women and 17 men) ranged in age from 34 to 80 years old (mean 57; median 56). The SEA was primary (i.e., due to haematogenous spread) in 16 patients (44%); it was secondary to elective spinal procedures, either injections or surgery, in 20 patients (56%). The duration of follow-up was 12-60 months (mean 36; median 37.5). The most common pathogen, Staphylococcus aureus, was found in 18 patients (50%). Patients with primary SEA had different underlying diseases and a wider range of pathogens than those with secondary SEA. Only five patients (14%) had no major comorbidity; 16 of the 20 patients with secondary SEA (44% of the overall group) had undergone spinal surgery before developing the SEA; the treatment of the SEA involved multiple surgical operations in all 16 of these patients, and spinal instrumentation in 5 (14%); 22 patients (61% of the overall group) recovered fully.
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  • 文章类型: Journal Article
    BACKGROUND: Over the last 15 years, bacterial meningitis has received considerable attention, including national guidelines, whilst viral central nervous system (CNS) infections have been relatively neglected. A recent pilot study suggested that management of patients with suspected viral encephalitis was often suboptimal.
    OBJECTIVE: To examine the relative incidence, clinical features and management of suspected acute CNS infections in adults across the NHS North West Region.
    METHODS: A multicentre cross-sectional retrospective cohort study at 10 hospitals across the region over 3 months (from September to December 2007). Following a screen of all patients who had cerebrospinal fluid (CSF) analysis or received intravenous aciclovir and/or third-generation cephalosporin, those with clinical features suspicious of a CNS infection were included. Management was compared with the national meningitis and regional encephalitis guidelines.
    RESULTS: Three hundred and eighty-five patients were screened; 217 patients had a suspected CNS infection and 44 (20%) had a CNS infection: 18 aseptic meningitis (one herpes simplex virus [HSV]-2), 13 purulent meningitis (four Streptococcus pneumoniae) and 13 encephalitis (three HSV-1). The median (range) time from admission to suspicion of CNS infection and to LP was longer for patients with encephalitis than meningitis [4 (0.3-312) vs. 0.3 (0.1-12) h, P<0.001, and 23 (4-360) vs. 12 (2-48) h, P=0.042, respectively]; and the median time to treatment was longer for aciclovir than cephalosporin [7 (0.5-312) vs. 3 (0.3-312) h, P=0.002].
    CONCLUSIONS: Encephalitis was as common as purulent meningitis, and HSV as common as Streptococcus pneumoniae. However, the management of patients with encephalitis was worse than meningitis. National encephalitis guidelines are needed.
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  • 文章类型: Journal Article
    BACKGROUND: In recent years, cranial ventricular catheters impregnated with antimicrobial agents have become available. Theoretically, they provide antibiotic prophylaxis locally without the associated complications of opportunistic nosocomial infections. This study aims to compare antibiotic impregnated catheters with conventional catheters coupled with systemic antibiotics.
    METHODS: Patients undergoing emergency neurosurgical operations were recruited. Patients were randomly assigned to antibiotic impregnated catheters (Bactiseal, Codman, Johnson & Johnson, Raynham, MA, USA) or conventional catheters coupled with systemic antibiotics.
    RESULTS: 184 neurosurgical patients were enrolled between April 2004 and December 2008. Mean duration of ventricular catheter was 10 days for both groups. The proportion of patients with nosocomial infection was not significantly different: 57% (51/90) in the Bactiseal group and 51% (48/94) in the conventional group (OR 1.3, 0.7 to 2.2). There were also no differences in secondary outcome measures (CSF infection, intensive care unit stay, acute hospital stay and functional outcome) between the two groups.
    CONCLUSIONS: Antibiotic impregnated catheters are as effective as systemic antibiotics in the prevention of CSF infection and their corresponding nosocomial infection rates are not significantly different. The study is registered at http://www.ClinicalTrials.gov (NCT00286104).
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  • 文章类型: Journal Article
    OBJECTIVE: We aim to correlate the frequency of infections after ventriculoperitoneal (VP) shunt placement in neonates with myelomeningocele (MMC) who did not receive prophylactic antibiotics to the timing of VP shunt placement and the frequency of cerebrospinal fluid (CSF) leakage at the MMC wound.
    METHODS: Fifty-nine newborns with MMC underwent VP shunt insertion in the period 1983-2007. We reviewed retrospectively all records.
    RESULTS: After MMC closure, 24 out of 59 newborns had an infection. The relative risk (RR; 95%) of having an infection is significantly higher [RR = 4,69 (1.145397-19.23568; P = .03761817)], and neuroinfection showed a tendency towards RR = 3.5 (.7067445-17.03112; P = .15414095) in newborns without symptomatic hydrocephalus at birth when we had a wait-and-watch policy (late shunt placement) compared with newborns with prompt shunt placement. The RR (95%) of having an infection [RR = 6,8 (3.314154-13.95228; P = 1.235e-07)] and also neuroinfections [RR = 4,76 (2.043019-11.09025; P = .00044478)] was highly significant if the child presented with MMC wound with CSF leakage before VP shunt insertion (Table 3).
    CONCLUSIONS: Centers with a conservative antibiotic policy should be even more careful to avoid CSF leakage before shunt placement as this gives a highly significant increased risk of both infections in total and neuroinfections, and they should reconsider this conservative policy in newborns with MMC due to the significantly high infection rate.
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