Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection.

OBJECTIVE: Intracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. METHODS: This study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. RESULTS: The CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952-1.000), 0.973 (95 % CI 0.949-0.998), 0.884 (95 % CI 0.823-0.946), and 0.819 (95 % CI 0.733-0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989-1.000), which was higher than those of the four indicators alone. CONCLUSION: The combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

Cerebrospinal fluid and plasma procalcitonin for the diagnosis of neonatal bacterial meningitis.

AIM: There is a paucity of data on cerebrospinal fluid (CSF) procalcitonin (PCT) to diagnose neonatal meningitis. We evaluated CSF PCT to diagnose bacterial meningitis among neonates with suspected sepsis. METHODS: Neonates undergoing lumbar puncture (LP) as part of sepsis workup were included. INDEX TESTS: CSF PCT, plasma PCT, CSF:plasma PCT ratio and CSF cytochemistry. Reference Standards: 'Definite meningitis' defined by positive CSF culture and/or gram stain and/or broad-based primer 16S rDNA polymerase chain reaction. 'Definite or probable' meningitis is defined as definite meningitis or abnormal cytochemistry. RESULTS: Of 216 eligible neonates, 18 had 'definite meningitis' and 37 'definite or probable meningitis'. Median (Q1 , Q3 ) CSF PCT level was significantly higher in 'definite meningitis' compared to 'no definite meningitis' (0.429 (0.123, 1.300) vs. 0.181 (0.119, 0.286) ng/mL respectively, P = 0.028). Likewise, it was significantly higher in 'definite or probable meningitis' compared to no meningitis (0.245 (0.136, 0.675) vs. 0.170 (0.116, 0.28), P = 0.01). The area under the receiver operator characteristics curve of CSF PCT level for definite meningitis was 0.656 and for 'definite or probable meningitis' 0.635. Paired comparisons of area under the receiver operator characteristics curve of CSF PCT with the other index tests showed no significant differences. Based on a priori cut-off of 0.2 ng/mL, CSF PCT level had a sensitivity (95% confidence interval) of 67% (50, 80), specificity 58% (54, 61), LR+ 1.6 (1.1, 2.0) and LR- 0.6 (0.3, 0.9). CONCLUSIONS: Higher values of CSF PCT are associated with neonatal bacterial meningitis. However, the diagnostic performance of CSF PCT is modest and not significantly different from standard tests.

Cerebrospinal Fluid Procalcitonin-A Potential Biomarker for Post-Craniotomy Bacterial Meningitis.

Background: The literature regarding the utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in the diagnosis of post-craniotomy bacterial meningitis and differentiating it from aseptic meningitis is sparse. Materials and Methods: CSF total WBC count, sugar, protein, and PCT were measured in febrile patients with suspected post-craniotomy meningitis during the first 30 days following an intradural cranial procedure for non-trauma indications. Patients were diagnosed as postoperative bacterial meningitis if CSF culture was positive (PBM, n = 28) or postoperative aseptic meningitis if CSF culture was sterile and there was no evidence of systemic infection (PAM, n = 31). CSF cytochemical parameters and PCT values were compared between the groups. Normal values of CSF PCT were obtained from 14 patients with noninfectious indications with hydrocephalus. Results: There was no significant difference in CSF total WBC count, sugar, and protein levels between PAM and PBM groups. The median PCT level in CSF in the normal group was 0.03 ng/mL (interquartile range [IQR] 0.02-0.07 ng/mL). CSF PCT in the PBM group (median 0.37 ng/mL, IQR 0.2-1.4 ng/mL) was significantly higher than normal values as well as PAM group (median 0.12 ng/mL, IQR 0.07-0.26 ng/mL (P = 0.0004). The area under the receiver operating characteristic (ROC) curve for CSF PCT was 0.767. A cutoff value of 0.12 ng/mL yielded a sensitivity of 85.7% (95% CI: 67.3% to 96%), specificity of 51.6% (95% CI: 33% to 69.9%), positive predictive value of 61.5% (95% CI: 51.9% to 70.3%), and negative predictive value of 80% (95% CI: 60.3.8% to 91.3%). Conclusions: CSF PCT assay in patients who are febrile during the first 30 days post-non-trauma neurosurgical procedures has a role in the early diagnosis of bacterial meningitis.

Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree.

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.

Procalcitonin measurement using antibody-conjugated fluorescent microspheres distinguishes atypical bacterial meningitis from viral encephalitis in children.

Examination of cerebrospinal fluid in atypical bacterial meningitis (ABM) is similar to that of viral encephalitis (VE), so ABM can easily be misdiagnosed as VE, which can delay diagnosis and treatment. We developed a simple, rapid hand-held lateral flow immunoassay detection system based on fluorescent microspheres (FMS) for procalcitonin (PCT) detection, which provides an indicator to differentiate between ABM and VE. With this novel method, the antigen-antibody reaction systems involve different species, making the test strips more stable than those utilizing one species. The strips exhibited a wide dynamic range (0.04-50 ng/mL) and good sensitivity (0.03 ng/mL). The function of PCT in the identification of ABM and VE in children was further studied. A significant difference in PCT levels was observed between the ABM and VE groups (P = 0.00) and between the ABM and the normal control groups (P = 0.00). PCT levels were not significantly different between the VE and normal control groups (P = 0.30). The area under the receiver operating characteristic curve of PCT for the diagnosis of ABM was 0.95. These findings collectively indicate the usefulness of the PCT detection method based on FMS for clinically differentiating between ABM and VE.

Higher Procalcitonin Level in Cerebrospinal Fluid than in Serum Is a Feasible Indicator for Diagnosis of Intracranial Infection.

Objective: To explore the value of the difference in procalcitonin (PCT) levels in serum and cerebrospinal fluid (CSF) for diagnosing intracranial infection in post-neurosurgical patients. Methods: Patients who were treated at our hospital after craniotomy from January 2015 to January 2019 were enrolled in this study. Twenty patients eventually diagnosed with intracranial infection were included in a study group and 22 patients with no intracranial infection were included in a control group. A t-test was used to compare the differences between serum and CSF PCT levels of PCT, and the diagnostic value of PCT was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The serum PCT levels in the study and control groups were 0. 10 ± 0. 03 ng/mL and 0. 09 ± 0. 03 ng/mL, respectively, and they were not substantially different between the groups. The CSF PCT level in the study group was substantially higher than that in the control group, with values of 0. 13 ± 0. 03 ng/mL and 0. 07 ± 0. 02 ng/mL, respectively. The CSF/serum PCT ratio in the study group was substantially higher than that in the control group, with values of 1. 31 ± 0. 19 and 0. 79 ± 0. 23, respectively. The areas under the ROC curve for serum PCT, CSF PCT and the CSF/serum PCT ratio were 0. 56, 0. 92, and 0. 95, respectively, resulting in a substantial difference among the three groups. Conclusion: CSF PCT may be a valuable marker for diagnosing intracranial infection in patients after neurosurgery; in particular, the specificity of CSF PCT is higher if the CSF PCT level is higher than the serum PCT level.

Effects of purulent meningitis on the changes of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor-1 (TIMP-1) in cerebrospinal fluid of neonates.

This study was aimed to investigate the changes of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor-1 (TIMP-1) in cerebrospinal fluid (CSF) of neonates with purulent meningitis. 195 cases (n=195) were divided into PM group (neonatal purulent meningitis), VM group (neonatal virus meningitis) and control group (healthy neonates). The expression levels of MMP-2 and TIMP-1 were detected by ELISA while the level of PCT was determined by chemiluminescence analyzer. The levels of MMP-2 and TIMP-1 in CSF and PCT in serum were compared in three groups and the correlation was discussed. The level of MMP-2 in CSF in 3 groups were statistically significant (F=16.126, P<0.05) similarly the level of TIMP-1 in CSF of 3 groups were statistically significant (F=16.093, P<0.05). The serum level of PCT in PM group was 14.73±2.14ng/l, in VM group was 9.06±1.05ng/l and in control group it was 0.37±0.12ng/l. The levels of MMP-2 and TIMP-1 in CSF were positively correlated with the serum level of PCT in both PM and VM group. The expression of MMP-2, TIMP-1 and serum PCT in CSF of newborns with purulent meningitis was increased. The findings suggest that MMP-2, TIMP-1 and PCT are involved in the occurrence and development of neonatal purulent meningitis.

The combination of cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 concentrations for the diagnosis of postneurosurgical bacterial meningitis: A prospective study.

BACKGROUND: The differential diagnosis between postneurosurgical bacterial meningitis and aseptic meningitis remains challenging both for the clinician and the laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. METHODS: This prospective cohort study included patients with suspected bacterial meningitis after neurosurgery. The patients were divided into two groups according to the diagnostic criteria of meningitis involving a postneurosurgical bacterial meningitis group and a postneurosurgical aseptic meningitis group. Four biomarkers, including cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 were assayed separately, and three algorithms were constructed using a linear combination. The area under the receiver operating characteristic curve was used to compare their performances. RESULTS: A cohort of 112 patients was enrolled in our study. Forty-three patients were diagnosed with postneurosurgical bacterial meningitis, and the cerebrospinal fluid values of their biomarkers were higher in patients with postneurosurgical bacterial meningitis than with postneurosurgical aseptic meningitis. The area under the receiver operating characteristic curves for the detection of postneurosurgical bacterial meningitis were 0.803 (95% confidence interval [CI], 0.724-0.883) for procalcitonin; 0.936 (95% CI, 0.895-0.977) for lactate; 0.771 (95% CI, 0.683-0.860) for interleukin-8; 0.860 (95% CI, 0.797-0.929) for interleukin-10; 0.937 (95% CI, 0.897-0.977) for the composite two-marker test; 0.945 (95% CI, 0.908-0.982) for the composite three-marker test and 0.954 (95% CI, 0.922-0.989) for the composite of all tests. The area under the receiver operating characteristic curves of the combination tests were greater than those of the single markers. CONCLUSIONS: Combining information from several markers improved the diagnostic accuracy in detecting postneurosurgical bacterial meningitis.

The Diagnostic and Antibiotic Reference Values of Procalcitonin for Intracranial Infection After Craniotomy.

OBJECTIVE: To evaluate values of cerebrospinal fluid (CSF) and serum procalcitonin (PCT) for diagnosis of intracranial infection after craniotomy and relationship between them and to explore value of PCT in guiding clinical use of antibiotics. METHODS: The incidence of intracranial infection in 21 patients undergoing craniotomy was reviewed. CSF samples and venous blood were collected for analysis. Diagnostic parameters were calculated via receiver operating characteristic curves, and inflammatory indicators were analyzed before and after administration of antibiotics in the infection group. As a control group, 32 patients without infection were recruited for the same measurements. RESULTS: CSF and serum PCT levels in the infection group were higher than levels in the noninfection group (P < 0.05), and diagnostic efficiency of CSF PCT (area under the curve = 0.86, diagnostic odds ratio = 41.40) was superior to serum PCT (area under the curve = 0.66, diagnostic odds ratio = 3.40). Diagnostic efficiency was more powerful when serial testing was used (specificity = 0.99, positive likelihood ratio = 37.10, diagnostic odds ratio = 54.45). All inflammatory indicators decreased after administration of antibiotics except CSF protein (P = 0.129), and no obvious correlation was seen between CSF and serum PCT. Dynamic change of PCT can be used as a reference for adjusting antibiotics. CSF PCT can also be used as an indicator to identify intracranial infection with gram-negative bacteria. CONCLUSIONS: CSF PCT is a good marker for intracranial infection and could be used to help confirm intracranial infection and provide guidance for clinical use of antibiotics when combined with serum PCT.

Diagnostic Value of Procalcitonin for Bacterial Meningitis in Children: A Comparison Analysis Between Serum and Cerebrospinal Fluid Procalcitonin Levels.

The aim of this study was to analyze and compare procalcitonin (PCT) levels in serum and cerebrospinal fluid (CSF) as tools for detecting bacterial meningitis (BM) in children. Serum and CSF PCT levels as well as albumin index (AI = CSF albumin/serum albumin × 1000) were measured from 29 BM, 25 viral meningitis (VM), and 47 non-meningitis patients. Differences between groups only for CSF PCT were significant. A stronger positive correlation between CSF PCT level and AI was observed in the BM patients ( R = 0.68, P < .001). As a predictor of BM, the area under the receiver operating characteristics curve for CSF PCT was greater than that of serum PCT (0.76 vs 0.67, P < .05) and a cutoff of ⩾0.085 ng/mL achieved 55.17% sensitivity and 95.83% specificity. High levels of CSF PCT may indicate loss of integrity of the blood-brain barrier; only CSF PCT has a diagnostic value for BM in children suspected meningitis.

A study on correlations of procalcitonin and interleukin-6 with viral meningitis.

OBJECTIVE: To study the change rules of inflammatory factors in cerebrospinal fluid (CSF) and serum of patients with viral meningitis. PATIENTS AND METHODS: 742 patients with suspected viral meningitis admitted to Department of Neurosurgery in our hospital from August 2012 to May 2016 were selected as research objects and retrospectively analyzed. 536 patients were diagnosed with viral meningitis by CSF with the lumbar puncture and brain computed tomography (CT), while the other 206 patients were diagnosed with non-infectious nervous system disease, as the control group. The levels of inflammatory factors interleukin-6 (IL-6) in peripheral blood and procalcitonin (PCT) in cerebrospinal fluid were detected and compared between two groups of patients. RESULTS: Compared with those in control group, the white blood cell (WBC) count, and levels of serum IL-6 and PCT in cerebrospinal fluid of patients with viral meningitis were all increased (p<0.01). PCT and IL-6 were positively correlated with viral meningitis (r=0.8267, 0.9234). The sensitivity of the two items was 77.81% and 81.32%, respectively, and the specificity was 90.53% and 88.64%, respectively. CONCLUSIONS: The levels of inflammatory factors IL-6 and PCT in serum and CSF of patients with viral meningitis are slightly increased. The detection of the expression levels of IL-6 and PCT in patients with viral meningitis is of great significance for the preliminary diagnosis and rehabilitation of viral meningitis.

The Diagnostic Dilemma of Traumatic Lumbar Puncture: Current Standing of Cerebrospinal Fluid Leukocyte Corrections and Our Experience With Cerebrospinal Fluid Biomarkers.

OBJECTIVE: To assess the diagnostic efficiency of cerebrospinal fluid markers of procalcitonin, lactate, and cerebrospinal fluid/serum lactate ratio for detecting bacterial meningitis during traumatic lumbar puncture, and to compare these markers with routinely used uncorrected and corrected leukocyte measurements. METHODS: Infants aged ≤90 days with traumatic lumbar puncture were prospectively studied. The diagnostic characteristics of cerebrospinal fluid assays of uncorrected and corrected leukocyte count, procalcitonin, lactate, and lactate ratio were described and compared. RESULTS: Considering the area under the curve (95% CI) analysis and standard cutoff values, the lactate-ratio (0.985 [0.964-0.989] at cutoff 1.2) had the best test indexes for identifying meningitis, followed by lactate (0.964 [0.945-0.984] at cutoff 2.2 mmol/L) and procalcitonin (0.939 [0.891-0.986] at cutoff 0.33 ng/mL) measurement, whereas the corrected total leukocyte count assay (0.906 [0.850-0.962] at cutoff 350 cells/mm3) had diagnostic properties moderately superior to uncorrected total leukocyte count measurement (0.870 [0.798-0.943] at cutoff 430 cells/mm3). CONCLUSION: Cerebrospinal fluid levels of procalcitonin, lactate, and lactate-ratio are reliable markers to diagnose bacterial meningitis in blood-contaminated cerebrospinal fluid.