Early Diagnosis and Treatment Monitoring of Native and Device-associated Meningitis Using D-lactate, a Pathogen-specific Diagnostic Biomarker in Cerebrospinal Fluid
试验速览
- 阶段
- 不适用
- 入组人数
- 842
- 试验地点
- 2
- 主要终点
- Performance of D-lactate test for the diagnosis of native and device-associated meningitis.
研究概览
简要总结
Device-associated meningitis is a severe complication after implantation of various central nervous system (CNS) devices such as ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts, external ventricular drains (EVD), lumbar drains (ELD) and intrathecal pumps. In contrast to native meningitis, these infections are hard to diagnose both clinically and on the laboratory basis due to (i) atypical clinical manifestation, (ii) overlapping inflammation following surgery, and (iii) common culture negativity due to previous antibiotic therapy and slow growth of low-virulent pathogens. Also, device-associated infections are difficult to differentiate from aseptic shunt failure (dysfunction) or "chemical meningitis" caused by underlying neurosurgical condition that prompted the placement of the CNS device (e.g. intracranial hemorrhage).
Both native and device-associated meningitis carry substantial morbidity and mortality. Rapid and reliable diagnosis of meningitis is critical for initiating and choosing optimal treatment and minimizing the brain damage. Since treatment is different in septic than aseptic meningitis, it is paramount to diagnose or exclude septic meningitis as soon as possible.
Several new diagnostic methods, such as cerebrospinal fluid (CSF) procalcitonin, interleukin-6 and polymerase chain reaction (PCR) have been proposed for rapid diagnosis of meningitis. However, insufficient sensitivity and/or specificity, long time until test result, and complexity in handling or interpretation of results limit their use in clinical routine.
In previous studies CSF D-lactate test showed good specificity and sensitivity in patients with native meningitis. This biomarker is pathogen-specific - in contrast to other currently used host-specific biomarkers (leukocyte count, L-lactate, procalcitonin). However, no study on effectiveness of D-lactate test for the diagnosis of device-associated meningitis has been performed.
Successful management of device-associated meningitis depends upon appropriate control of the infectious complications. To deal with such complications, adequate assessment and prediction of the clinical course are needed. Another use of D-lactate test could be his role as prognostic factor of the clinical course of device-associated meningitis.
详细描述
Study aim Evaluation of the analytical and clinical performance (sensitivity, specificity, positive and negative predictive value, accuracy) of a novel, pathogen-specific biomarker D-lactate in the cerebrospinal fluid (CSF) for the diagnosis and treatment monitoring of native and device-associated meningitis. The performance of CSF D-lactate will be compared with currently used conventional CSF culture and biomarkers, using standard definition criteria for infection (native and device-associated meningitis).
Specific aims
- Aim 1. Determination of the performance of D-lactate test for the diagnosis of device-associated meningitis and native meningitis in serially collected CSF samples through lumbar/ventricular puncture (pre- or intra-operatively), external ventricular drainage (EVD), lumbar drainage (ELD) and shunt aspiration.
- Aim 2. Evaluate the optimal cut-off value of CSF D-lactate test for the diagnosis of device-associated and native meningitis using the existing definition criteria.
- Aim 3. Evaluation of performance of D-lactate test for the diagnosis of device-associated and native meningitis compared to standard tests (culture, gram stain, cerebrospinal fluid leukocyte count & differential, CSF lactate, CSF glucose, CSF-to-blood glucose ratio, CSF total protein, multiplex PCR) and novel biomarkers (CSF procalcitonin, alpha-defensin - ELISA, interleukin-6).
Study population:
Included will be consecutive patients with suspected device-associated meningitis and native meningitis treated in our institution. CSF will be aspirated following the routine diagnostic procedure. During conduction of this study no additional invasive or non-invasive examinations will be performed. The results obtained in this clinical investigation will not influence the diagnostic or treatment decisions for the patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Performance of D-lactate test for the diagnosis of native and device-associated meningitis.
时间窗: up to 30 months
Determined performance (D-lactate cut-off value, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio) of D-lactate test. * The Mann-Whitney test and Spearman's correlation will be applied to analyze the quantitative variables. Youden's J statistic will be used for determining optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. * The area under the ROC curves will be calculated to compare the D-lactate test performance.
次要结局
- Performance of the D-lactate test in comparison with standard tests for the diagnosis of native and device-associated meningitis.(up to 30 months)
- Treatment monitoring using D-lactate test (as a predictor of treatment success / failure).(up to 30 months)
研究者
Andrej Trampuz
PD Dr. med, Head of Septic Surgery Unit
Charite University, Berlin, Germany