The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis

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Abstract

Objectives

Distinguishing between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. This study aims to evaluate the combined diagnostic value of CSF procalcitonin and lactate as novel PNBM markers in hospitalized post-neurosurgery patients.

Design and methods

This study was performed using CSF samples, collected by lumbar puncture, from 178 PNBM-suspected patients enrolled in a retrospective clinical study. The levels of CSF procalcitonin and lactate were appropriately assayed and the combined diagnostic value of these markers was assessed using receiver operating characteristic (ROC) curves, a two by two table, and non-parametric tests.

Results

Fifty of the 178 patients were diagnosed with PNBM, based on the clinical symptoms and laboratory results. These PNBM patients showed significantly elevated levels of CSF procalcitonin and CSF lactate compared with the non-PNBM group (p < 0.001 for both). It was revealed that the cut-off values for the diagnosis of PNBM were: 0.075 ng/mL (sensitivity, 68%; specificity, 73%) for procalcitonin and 3.45 mmol/L (sensitivity, 90%; specificity, 85%) for lactate. A serial test combining the levels of these two markers showed decreased sensitivity (64%) and increased specificity (91%), compared with either marker alone. In contrast, a parallel test combining the levels of these both markers showed increased sensitivity (96%) and decreased specificity (65%), compared with either marker alone.

Conclusion

Our study shows that the combined use of CSF procalcitonin and lactate can reliably distinguish between PNBM and non-PNBM and can be included in the design of diagnostic approaches to circumvent the shortcomings of conventional methods.

Introduction

Bacterial meningitis after neurosurgical procedures is relatively uncommon with a low incidence of about 0.3%–1.5% [1], but it is a severe and life threatening infection with a high mortality that ranges from 20 to 50% [2]. At present, post-neurosurgery bacterial meningitis (PNBM) is diagnosed based on the criteria proposed by the Center for Disease Control and Prevention (CDC) [3], the Massachusetts General Hospital (MGH) [4], the Infectious Diseases Society of America (IDSA) and our local criteria. Our criteria included clinical symptoms, various biochemical parameters of the cerebrospinal fluid (CSF) and the blood, and the CSF bacterial culture, which constitutes the golden standard for the diagnosis of bacterial meningitis. However, the low level of the various blood and CSF biochemical parameters does not always rule out bacterial meningitis and should be used with caution. Actually, PNBM and aseptic meningitis share some clinical symptoms and physical signs, including headache, fever, neck stiffness, and vomiting [5]. In addition, hemorrhage, surgical procedure, trauma, and bone dust all appear to trigger an inflammatory response that mimics the bacterial meningitis CSF changes and fail to demonstrate a high diagnostic accuracy [5], [6]. Moreover, the time-consuming nature and propensity to contamination of the CSF bacterial culture contribute to the low detection rate of positive culture, reported to be about 6–9% [7], [8], [9]. Given all these influencing factors, it is necessary to introduce novel diagnostic markers to assist in the diagnosis of PNBM in order to offer more diagnostic options and to evaluate the utility of antibiotic drugs.

It has been established that the production of the CSF lactate by the astrocytes is triggered by bacterial infection. Recently, the CSF lactate has been shown to be correlated with bacterial infection and was suggested as a potential marker for distinguishing between infection and inflammation, as well as a biomarker for PNBM for its excellent discriminatory power [10], [11].

Serum procalcitonin has also been proposed as a novel biomarker with high sensitivity and specificity for both diagnostic and prognostic values in various severe infections [12], [13], [14]. Although this biomarker has been studied as an aid to classify infections according to severity and to guide therapy durations the clinical value of CSF procalcitonin in the differential diagnosis of PNBM is rarely investigated. Thus, whether the combined use of CSF procalcitonin and lactate as biomarkers could improve the diagnostic efficacy is still unclear.

Section snippets

Patients

The current study retrospectively analyzed 178 patients who underwent neurosurgery at our institute between October 2013 and March 2014. This study was approved by our Institutional Review Board and written informed consent was obtained from all the patients enrolled. Patients who showed clinical symptoms of bacterial meningitis such as fever, headache, neck stiffness, and disturbance of consciousness, within 48 to 72 h after surgery were subjected to lumbar puncture in order to collect CSF

Results

The 178 patients enrolled in this study were divided into 50 patients to the PNBM group and 128 to the non-PNBM group. The values for each of the various parameters were not normally distributed when examined by category. The medians of the parameters for diagnosis (age, sex, CSF procalcitonin, CSF lactate, CSF WBC count and polykaryocyte percentage, CSF protein, CSF chloride, and CSF glucose) were compared and the comparison results are given in Table 1. In the PNBM group, the median of the

Discussion

Conventional laboratory biomarkers are always applied to the diagnosis of PNBM, including the CSF bacterial culture, polymerase chain reaction (PCR) testing of CSF bacteria, WBC count, protein, glucose, and chloride in the CSF [16]. Although the CSF bacterial culture remains the golden standard, the percent positive results are only about 10% due to a variety of reasons, including the low amount and contamination of CSF sample, time constraints, and antibiotic drug administration [7], [9].

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

We would like to acknowledge the support from the Center of Brain Tumor, Beijing Institute for Brain Disorders (BIBD-PXM2013_014226_07_000084).

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    This work was supported by the Natural Science Foundation of Beijing (7142051), the High Level Technical Talent Development of Beijing Health System (2013-3-052), the State Science and Technology Support Program—Application Evaluation of Basic Biological and Chemical Equipment (3013BAI17B04) and the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People's Republic of China (2013BAI09B03).

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