Cerebrospinal Fluid WBC Research Articles

A multicenter epidemiological study of neonatal bacterial meningitis in parts of South China

Objective: To analyze the epidemiological characteristics (pathogenic bacteria distribution, clinical menifestations and outcomes) of neonatal bacterial meningitis in parts of Guangdong Province and Guangxi Zhuang Autonomous Region. Methods: A retrospective epidemiological study was carried out in the infants with bacterial meningitis admitted to 12 hospitals in Guangdong Province and Guangxi Zhuang Autonomous Region from January 2011 to December 2016. The distribution of pathogenic bacteria and epidemiological characteristics were analyzed during different periods (2011-2012, 2013-2014, 2015-2016), between early-onset and late-onset cases, preterm infants and term infants. Numeric variables between groups were compared with Student's t test. Non-numeric variables were analyzed with χ(2) test. Results: A total of 838 cases which met the criteria of neonatal bacterial meningitis were admitted during the study period, within which males were 545 and females were 293, with an average onset age of 8 (2, 16) days and diagnosed at the age of 14 (8, 20) days. Blood or CSF cultures were positive in 249 infants (29.7%), with Streptococcus agalactiae (GBS), Escherichia coli (E. coli), Coagulase negative staphylococcus (CoNS) as the most common bacteria. The culture positive rate were 29.6% (47/159), 33.6% (85/253) and 27.5% (117/426) respectively in the periods of 2011-2012, 2013-2014, and 2015-2016, without significant differences among groups (χ(2)=2.860, P=0.239). In the culture positive cases, there were no significant differences between the Gram-negative bacilli and Gram-positive cocci proportion in the three different periods (χ(2)=2.081, P=0.353). The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 33.0% (64/194) and 28.7% (185/644) in early-onset and late-onset bacterium meningitis infants (χ(2)=1.297, P=0.255). The differences of Gram-negative bacilli and Gram-positive cocci proportion in the two groups were statistically significant (15/49 vs. 83/103, χ(2)=8.967, P=0.003), while the most common bacteria was GBS in both groups. The positive rates of CSF culture and blood culture were 26.9% (57/212) and 30.7% (192/626) in preterm infants and term infants, without significant difference between the two groups (χ(2)=0.830, P=0.362). While the differences of Gram-negative bacilli and Gram-positive cocci proportion in the two groups were significant (40/18 vs. 58/134, χ(2)=28.074, P=0.000), with E. coli in preterm infants while GBS in term infants. There were 45 cases (5.4%) of which cerebrospinal fluid (CSF) WBC counts were less than 20×10(6)/L when bacterial meningitis was diagnosed, among them 5 cases had positive CSF culture; there were 728 cases (90.9%, 728/801) of CSF WBC≤20×10(6)/L at discharge. The positive rate of blood culture and CSF culture were both Lower in cases treated with antibiotics > 24 hours and≤24 hours before diagnosis, with significant difference (χ(2)=19.668, P=0.000). Fever was the most common clinical manifestation (633 cases, 75.5%), and hydrocephalus was the most common complication (167 cases, 19.9%), which was seen more commonly in Gram-negative bacillus cases(χ(2)=4.190, P=0.041). There were 801 infants (95.6%) who were cured or improved at discharge but 13 deaths (1.6%). The median course of antibiotic before and after diagnosis were 3 days and 20 days, respectively. Single antibiotics was used in 255 (30.4%), mainly meropenem (146 cases, 57.3%) or third generation cephalosporin (67 cases, 26.3%), while combination treatment was used in 583 cases(69.6%), mainly meropenem and third generation cephalosporin (302 cases, 51.8%), or Penicillin (or vancomycin) and third generation cephalosporin (115 cases, 19.7%). There was no significant difference in efficacy between single and combined antibiotics treatment groups (P all>0.05). Conclusions: The most common bacteria of neonatal bacterial meningitis were GBS, E. coli and CoNS in parts of South China. GBS was the most common pathogen in both early-onset and late-onset bacterial meningitis, also most common in term infants. While the most common bacteria in preterm infants was E. coli. Fever was the most common clinical manifestation and hydrocephalus was the main complication. Neonatal bacterial meningitis should not be excluded if the CSF WBC is within normal range. The positive rate of CSF or blood culture decreased significantly if antibiotic is used more than 24 hours before diagnosis. Single antibiotics for sensitive bacteria is as effective as combined antibiotics treatment.

Guidance value of cerebrospinal fluid and serum procalcitonin in the ventricular catheter indwelling time of intracranial pressure monitoring

Objective To explore the guidance value of cerebrospinal fluid(CSF) and serum procalcitonin(PCT) in the ventricular catheter indwelling time of intracranial pressure monitoring(ICP). Methods Fifty-eight cases patients with moderate and severe craniocerebral trauma who were given ICP ventricular catheter and external ventricular drainage(EVD) were selected, 5 ml CSF and 2 ml venous blood were collected at operation, 1st, 7th, 14th d after operation.The change of CSF and serum PCT and WBC levels were compared among different time, the correlation among each indicators and diagnosis value for intracranial infection were analyzed. Results The level of CSF and serum PCT and WBC increased with the lengthen of ventricular catheter indwelling time(CSF PCT: (0.09±0.02) μg/L of operation, (1.17±0.25) μg/L of 14 d after the operation; CSF WBC: (24.33±12.75)×106/L of operation, (431.52±140.26)×106/L of 14 d after the operation; serum PCT: (0.16±0.05) μg/L of operation, (4.57±1.41) μg/L of 14 d after the operation; serum WBC: (4.14±0.46)×106/L of operation, (14.24±3.05)×106/L of 14 d after the operation; P<0.05). The CSF PCT was positively correlated with CSF WBC and serum PCT(r=0.614, 0.711, P<0.05). The diagnostic sensitivity of CSF and serum PCT for prognosis of intracranial infection were 95.2%, 81.0%, the specificity were 94.6%, 78.4%, the specificity of CSF PCT was significantly higher than that of serum PCT(P=0.041). Conclusion CSF and serum PCT has high early diagnosis value for intracranial infection in patients with ICP ventricular catheter, which can contribute to guide the reasonable timing of tube drawing, brings out the best of ICP and cerebrospinal fluid drainage, improve the level of treatment in patients with traumatic brain injury. Key words: Cerebrospinal fluid; Serum procalcitonin; Intracranial pressure monitoring; Intracranial infection

Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture

We determine the optimal correction factor for cerebrospinal fluid WBC counts in infants with traumatic lumbar punctures. We performed a secondary analysis of a retrospective cohort of infants aged 60 days or younger and with a traumatic lumbar puncture (cerebrospinal fluid RBC count ≥10,000 cells/mm3) at 20 participating centers. Cerebrospinal fluid pleocytosis was defined as a cerebrospinal fluid WBC count greater than or equal to 20 cells/mm3 for infants aged 28 days or younger and greater than or equal to 10 cells/mm3 for infants aged 29 to 60 days; bacterial meningitis was defined as growth of pathogenic bacteria from cerebrospinal fluid culture. Using linear regression, we derived a cerebrospinal fluid WBC correction factor and compared the uncorrected with the corrected cerebrospinal fluid WBC count for the detection of bacterial meningitis. Of the eligible 20,319 lumbar punctures, 2,880 (14%) were traumatic, and 33 of these patients (1.1%) had bacterial meningitis. The derived cerebrospinal fluid RBCs:WBCs ratio was 877:1 (95% confidence interval [CI] 805 to 961:1). Compared with the uncorrected cerebrospinal fluid WBC count, the corrected one had lower sensitivity for bacterial meningitis (88% uncorrected versus 67% corrected; difference 21%; 95% CI 10% to 37%) but resulted in fewer infants with cerebrospinal fluid pleocytosis (78% uncorrected versus 33% corrected; difference 45%; 95% CI 43% to 47%). Cerebrospinal fluid WBC count correction resulted in the misclassification of 7 additional infants with bacterial meningitis, who were misclassified as not having cerebrospinal fluid pleocytosis; only 1 of these infants was older than 28 days. Correction of the cerebrospinal fluid WBC count substantially reduced the number of infants with cerebrospinal fluid pleocytosis while misclassifying only 1 infant with bacterial meningitis of those aged 29 to 60 days.

White Cell Indices and CRP: Predictors of Meningitis in Neonatal Sepsis?

Background Objective: To evaluate the utility of specific cut-off values for C- reactive protein (CRP) and immature-to-total neutrophil ratio (I/T) as screening tests for meningitis in culture negative early onset sepsis (EOS). Materials and Methods Retrospective chart review of 97 newborns with culture negative sepsis who had lumbar puncture performed as part of the sepsis evaluation in a level IIIB NICU at an academic medical center serving a predominantly minority population. Meningitis was defined as either a positive cerebrospinal fluid (CSF) culture or CSF WBC count ≥30/mm. The outcome measures were the sensitivity, specificity and predictive values of CRP >40 mg/L and I/T ratio >0.3 for diagnosing meningitis in newborns with EOS. Results The sensitivity, specificity and positive predictive value of I/T ratio >0.3, CRP >40 mg/L or a combination of these two either at 12 or 24 hours of life were very poor. However, CRP >40 mg/L alone or in combination with I/T ratio >0.3 at both 12 and 24 hours of life had negative predictive values of 85-90%. Conclusion CRP >40 mg/L and/or I/T ratio >0.3 have poor sensitivity, specificity and predictive values as screening tests for meningitis in culture negative early onset sepsis.

Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection.

BackgroundOcular syphilis is reemerging as an important cause of uveitis in the new era of common co-infection with HIV. This study will reveal the clinical and laboratory characteristics in the group of individuals co-infected with ocular syphilis and HIV compared with HIV-negative individuals. In this retrospective observational case series, medical records of patients diagnosed with ocular syphilis with serologic support from 2008 to 2014 were reviewed. Ocular and systemic manifestation and laboratory profiles were reviewed.ResultsTwenty-nine eyes of 16 consecutive patients (10 HIV-positive and 6 HIV-negative) were included. All patients were males, and mean age of onset for ocular syphilis was 43 (mean 42.65 ± 13.13). In both HIV-positive and HIV-negative groups, ocular manifestations of syphilis were variable including anterior uveitis (4 eyes), posterior uveitis (8 eyes), panuveitis (13 eyes), and isolated papillitis (4 eyes). In HIV-positive patients, panuveitis was the most common feature (12/18 eyes, 67 %) and serum rapid plasma reagin (RPR) titers were significantly higher (range 1:64–1:16,348; mean 1:768; p = 0.018) than in HIV-negative patients. Upon the diagnosis of ocular syphilis in HIV-positive patients, HIV-1 viral load was high (median 206,887 copies/ml) and CD4 cell count ranged from 127 to 535 cells/ml (mean 237 ± 142; median 137). Regardless of HIV status, cerebrospinal fluid (CSF) exam was frequently abnormal: positive CSF fluorescent treponemal antibody absorption (FTA-ABS) or Venereal Disease Research Laboratory (VDRL) test results in seven patients or either elevated CSF WBC count or elevated CSF protein in six patients.ConclusionsOur results reveal that the patients with ocular syphilis with high serum RPR titers may have concomitant HIV infection requiring further testing for HIV status and ocular syphilis is likely associated with the central nervous system involvement and therefore needs to be managed according to the treatment recommendations for neurosyphilis.

Significance of routine cerebrospinal fluid analysis in subarachnoid hemorrhage.

The aim of this paper was to determine the diagnostic value of cerebrospinal fluid (CSF) analysis in the setting of aneurysmal subarachnoid hemorrhage (aSAH), hypothesizing that CSF analysis is only critical in confirming suspected infection and may be useful in predicting and/or detecting delayed cerebral ischemia (DCI). Retrospective review of consecutive adult patients diagnosed with aSAH from 1/2000 to 12/2013 at Mayo Clinic, Rochester, MN, USA with cerebral aneurysm(s) identified by vascular imaging, and CSF drawn within 14 days of the date of hemorrhage. We identified 741 patients during the study period, 167 met inclusion criteria and 356 samples were collected. First Median CSF samples were taken 5 (4-8) days postbleed. Multiple samples were taken in 94 (54.5%) patients and the mean number of samples per patient was 2.1. Ventriculitis, confirmed by growth of organism from CSF culture was present in 2 (1.2%) patients and one patient (0.6%) developed meningitis. CSF WBC count remained elevated throughout the 14 days, even when corrected for red blood cell count (RBC). Peak CSF RBCs occurred 2-4 days post bleed, and then gradually normalized. Maximum CSF RBCs did not correlate with modified Fisher grades (P=0.422). Delayed cerebral ischemia (DCI) was present in 86 (51.5%) patients and there was no difference in the CSF profile of patients with DCI compared with those without. Routine CSF sampling for cell count and chemistry in the setting of temporary diversion following aSAH appears to have little clinical benefit beyond the evaluation for infection.

The Effect of Traumatic Lumbar Puncture on Hospitalization Rate for Febrile Infants 28 to 60 Days of Age

The authors measured the effect of a traumatic or unsuccessful lumbar puncture (LP) on the management of febrile infants. This was a 10-year retrospective cross-sectional study of low-risk infants by the "Boston" criteria 28 to 60days of age presenting to the emergency department for evaluation of fever. "Normal LP" infants had cerebrospinal fluid (CSF) WBC < 10×10(6) cells/L. "Traumatic" or "unsuccessful LP" infants had CSF red blood cell count ≥ 10×10(9) cells/L or no CSF cell counts obtained, respectively. A serious bacterial infection (SBI) was defined as growth of a bacterial pathogen from culture. The hospitalization and SBI rates were compared between infants with normal versus traumatic or unsuccessful LPs. Of the 929 study infants, 756 (81.4%) had normal LPs, and 173 (18.6%) had traumatic or unsuccessful LPs. Infants with traumatic or unsuccessful LPs had a higher hospitalization rate (72.3% traumatic or unsuccessful LP vs. 18.1% normal LP; difference= 54.1%; 95% confidence interval [CI] = 46.4% to 60.8%), but a similar SBI rate (2.9% vs. 4.1%; difference= 1.2%; 95% CI = -2.7% to 3.6%). No infant had proven bacterial meningitis (0% risk, 95% CI = 0 to 0.3%). Low-risk infants aged 28 to 60days with traumatic or unsuccessful LPs are more frequently hospitalized, although SBI rates were similar to those of infants with normal LPs.

Study of the risk factors in disease progression and concentrations of VEGF and VCAM-1 in hand foot and mouth disease combined with encephalitis

Objective To explore the risk factors in disease progression and the significance of vascular endothelial growth factor （ VEGF ） and vascular intercellular adhesion molecule-1 （ VCAM-1 ） in hand foot and mouth disease （ HFMD） combined with encephalitis .Methods Altogether 92 subjects with HFMD were enrolled in the study and were divided into four groups , including group A （ ordinary group with no complication ） , group B （ severe group with complication ） , group C （ critical group with complication ） , group D （ recovery group with complication ） .Concentrations of VEGF and VCAM-1 in serum and cerebro-spinal fluid were detected by double antibody sandwich ELISA method .Multiple factors logistic regression＆nbsp;analysis was performed to analyze main risk factors in disease progression for two combinations , one for ordi-nary group and severe group , the other for severe group and critical group .The results were analyzed by SPSS16.0 statistical software.Results The concentration of VEGF and VCAM-1 in serum and cerebrospi-nal fluid had statistically significant differences among the four groups , but there was no significant difference between group A and group D , and between group B and group C .In addition , the statistically significant factors for prediction of disease progression were duration of fever , limb shaking, cerebrospinal fluid WBC , cerebrospinal fluid protein and EV 71 IgM between ordinary group and severe group , and cerebrospinal fluid WBC, respiratory rate and heart rate between severe group and critical group .The multiple factors logistic regression analysis revealed that limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum were the main risk factors for disease progression from ordinary to severe （P=0.071, 0.019, 0.020, 0.025 and OR=147.629, 26.572, 5.958, 6.345）.And increased heart rate indicated the progression from se-vere to critical with P value of 0.001 and OR value of 2.69.Conclusion （1） Compared with group A, VEGF and VCAM-1 in serum and cerebrospinal fluid were highly expressed in patients with HFMD combined with encephalitis .Therefore , VEGF and VCAM-1 could be used as diagnostic criteria for auxiliary diagnosis of encephalitis in patients with HFMD and reflect the severity and prognosis to a certain extent .（ 2 ） Risk factors like limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum would be helpful to early diagnosis of severe patients .Increased heart rate would be a significant factor for identification of patients with critical disease , according to which a timely treatment would be provided to prevent from worse . Key words: Hand foot and mouth disease combined with encephalitis; Vascular endothelial growth factor; Vascular cell adhesion molecule-1; Disease progression; Risk factor

P2.193 Ocular Syphilis in HIV-Negative Patients

BackgroundOcular syphilis is reemerging in the last decade in several countries around the world. However, little is known about the clinical and Cerebrospinal fluid (CSF) characteristics in HIV-negative individuals.MethodsWe retrospectively...

Leptomeningeal Carcinomatosis in Non–Small-Cell Lung Cancer Patients: Impact on Survival and Correlated Prognostic Factors

The incidence of leptomeningeal carcinomatosis (LC) has increased in patients with metastatic non-small-cell lung cancer (NSCLC) because of recent improvements in survival. The clinical features and prognostic factors of LC in NSCLC patients, however, have not been well identified. The aim of this study was to identify the clinical features and prognostic factors of NSCLC patients with LC. One hundred and forty-nine consecutive NSCLC patients with cytologically proven LC diagnoses between 2001 and 2009 at Samsung Medical Center were retrospectively reviewed. The median age was 58 years (range, 34-80) with most patients (135, 95%) having histology indicating adenocarcinoma. Twenty-six patients (17.4%) had LC at the initial presentation of lung cancer. Treatment for LC consisted of intrathecal chemotherapy (ITC) alone in 44 patients, ITC plus systemic therapy in 18 patients, ITC plus radiotherapy in 29 patients, all three treatments in 18 patients, and other treatments without ITC in 20 patients. Twenty patients received only supportive care. The median follow-up duration was 34 months and the median overall survival from diagnosis of LC was 14 weeks (95% confidence interval [CI] 12, 16). In univariate analysis, encephalopathy, Eastern Cooperative Oncology Group (ECOG) performance status, low initial cerebrospinal fluid (CSF) glucose, high initial CSF protein, high initial CSF white blood cell count, treatment with ITC, systemic therapy with epidermal growth factor receptor tyrosine kinase inhibitors or cytotoxic chemotherapy, whole-brain radiotherapy (WBRT), ventriculoperitoneal (VP) shunt operations, and negative cytologic conversion after ITC were identified as variables that had prognostic influence on survival. In multivariate analysis, poor ECOG performance status (p = 0.026), high protein level of CSF (p = 0.027), and high initial CSF WBC count (p = 0.015) remained significant predictors of poor prognosis for survival, whereas ITC (p < 0.001), EGFR-TKI use (p = 0.018), WBRT (p = 0.009), and VP shunt operation (p = 0.013) remained significant predictors of favorable prognosis for survival. Even though the prognosis of LC from NSCLC is poor, small subsets of these patients survive longer. Our results suggest that more active treatment strategies including ITC, WBRT, and EGFR-TKI use might improve clinical outcomes in NSCLC patients with LC and good performance status, low initial CSF protein and WBC counts.

CXCL13 is a biomarker of inflammation in multiple sclerosis, neuromyelitis optica, and other neurological conditions

CXCL13, a B-cell chemokine, has been proposed as a biomarker in a variety of conditions, some of which can mimic multiple sclerosis and can have very high levels. In this case-control study, cerebrospinal fluid (CSF) CXCL13 was elevated in multiple sclerosis, neuromyelitis optica and other inflammatory neurological controls compared with noninflammatory controls. Levels did not differentiate disease groups. For all subjects taken together, CSF CXCL13 correlated with CSF WBC, oligoclonal band numbers, CSF protein, EDSS, and neurofilament levels. In subgroup analyses, CSF CXCL13 correlated with CSF WBC in neuromyelitis optica and IgG index in multiple sclerosis. Additionally, serum CXCL13 was elevated in neuromyelitis optica.

Cerebrospinal fluid abnormalities in HIV-negative patients with secondary and early latent syphilis and serum VDRL ≥ 1:32

Background:Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS) by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Recent studies indicated that serum RPR ≥ 1:32 are associated with higher risk of reactivity of CSF VDRL.Aims:The main aim of the current study was to assess cerebrospinal fluid serological and biochemical abnormalities in HIV negative subjects with secondary and early latent syphilis and serum VDRL ≥ 1:32.Materials and Methods:Clinical and laboratory data of 33 HIV-negative patients with secondary and early latent syphilis, with the serum VDRL titer ≥ 1:32, who underwent a lumbar puncture and were treated in Department of Dermatology at Jagiellonian University School of Medicine in Cracow, were collected.Results:Clinical examination revealed no symptoms of CNS involvement in all patients. 18% (n = 6) of patients met the criteria of confirmed neurosyphilis (reactive CSF-VDRL). In 14 (42%) patients CSF WBC count ≥ 5/ul was found, and in 13 (39%) subjects there was elevated CSF protein concentration (≥ 45 mg/dL). 10 patients had CSF WBC count ≥ 5/ul and/or elevated CSF protein concentration (≥ 45 mg/dL) but CSF-VDRL was not reactive.Conclusions:Indications for CSF examination in HIV-negative patients with early syphilis are the subject of discussion. It seems that all patients with syphilis and with CSF abnormalities (reactive serological tests, elevated CSF WBC count, elevated protein concentration) should be treated according to protocols for neurosyphilis. But there is a need for identification of biomarkes in order to identify a group of patients with syphilis, in whom risk of such abnormalities is high.

Clinical and Analytical Characteristics and Short-Term Evolution of Enteroviral Meningitis in Young Infants Presenting With Fever Without Source

The objective of this study was to describe the characteristics of the enteroviral meningitis diagnosed in a pediatric emergency department among infants younger than 3 months with fever without source and its short-term evolution. This was a retrospective, cross-sectional, 6-year descriptive study including all infants younger than 3 months who presented with fever without source and who were diagnosed with enteroviral meningitis. A lumbar puncture was practiced at their first emergency visit in 398 (29.5%) of 1348 infants, and 65 (4.8%) were diagnosed with enteroviral meningitis, 33 of them (50.7%) between May and July. Among these 65 infants, 61 were classified as well-appearing; parents referred irritability in 16 (25.3%) of them (without statistical significance when compared with infants without meningitis). Forty-one (63.0%) had no altered infectious parameters (white blood cell [WBC] count between 5000 and 15,000/μL, absolute neutrophil count less than 10,000/μL, and C-reactive protein less than 20 g/L), and 39 (60%) had no pleocytosis. All of the 65 infants recovered well, and none of them developed short-term complications. The symptoms in infants younger than 3 months with enteroviral meningitis were similar to those in infants with a self-limited febrile process without intracranial infection. C-reactive protein and WBC count were not good enteroviral meningitis predictors. Cerebrospinal fluid WBC count was normal in many of these infants, so performing a viral test is recommended for febrile infants younger than 3 months in which a lumbar puncture is practiced during warm months. The short-term evolution was benign.

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting

Cryptococcal meningitis (CM) and tuberculous meningitis (TBM) are common in HIV-infected adults in Africa and difficult to diagnose. Inaccurate diagnosis results in adverse outcomes. We describe patterns of meningitis in a Malawian hospital, focusing on features which differentiate CM and TBM with the aim to derive an algorithm using only clinical and basic laboratory data available in this resource-poor setting. Consecutive patients admitted with meningitis were prospectively recruited, clinical features were recorded and cerebrospinal fluid (CSF) was examined. A total of 573 patients were recruited, and 263 (46%) had CSF consistent with meningitis. One hundred and twelve (43%) had CM and 46 (18%) had TBM. CM was associated with high CSF opening pressure and low CSF leukocyte count. Fever, neck stiffness and reduced conscious level were associated with TBM. A diagnostic index was constructed demonstrating sensitivity 83%and specificity 79% for the differentiation of CM and TBM. An algorithm was derived with 92% sensitivity for the diagnosis of CM, but only 58% specificity. Although we demonstrate features associated with CM and TBM, a sufficiently sensitive and specific diagnostic algorithm could not be derived, suggesting that the diagnosis of CM and TBM in resource-limited settings still requires better access to laboratory tools.

Neonatal bacterial meningitis and dexamethasone adjunctive usage in Nigeria.

Neonatal bacterial meningitis is devastating, with attendant high mortality and neurological sequelae. We, therefore, aimed to delineate its current incidence, etiologic, clinical, laboratory spectra, and the effect of steroid therapy on the outcome. Babies admitted from 1992 to 1995 in the Special Care Baby Unit of the University of Maiduguri Teaching Hospital, Maduguri, Nigeria, with bacterial meningitis were studied prospectively. Neonatal bacterial meningitis was confirmed if the cerebrospinal fluid (CSF) microbiological, chemical, immunological and clinical criteria were satisfied. Detailed neurological follow-up was made. Sixty-nine cases of neonatal bacterial meningitis were encountered, (25 were early-onset, and 44 late-onset); the incidence was 6.5/1000 live births. 22 Positive CSF cultures were grown in early-onset meningitis, and 28 in late-onset disease. Low birth weight showed higher risk of bacterial meningitis and it was significantly more likely in the preterm. X2 = 24.19, p = 0.000001). Gram-negative pathogens were more isolated (28/50, 56%); Escherichia coli (11) being the commonest, while of the Gram-positive pathogens Staphylococcus aureus was most predominant overall (13/50). Concomitant blood culture was positive in 39/50 (78%), inclusive of all 22 "definite" early-onset disease. The CSF WBC was minimally raised (25-30 x 10(6)/L) in 11 (22%) of "definite" neonatal bacterial meningitis. Detection of unusual pathogens was noteworthy: N. meningitidis (2) and H. influenzae (2), contributing 0.6 and 2.2 per 1000 live births and admissions, respectively. Overall mortality was 24.6%. Of the forty survivors, 9 (22.5%) had neurological sequelae: sensorineural hearing deficit (3), hydrocephalus (2), subdural effusion (2), hemiparesis (1), afebrile (recurrent) seizure (1), and there was reduced developmental quotients at 24 months follow-up in 33. Dexamethasone therapy decreased mortality significantly; p = 0.0004. The new information highlighted by this research includes the lack of Group B Streptococcus isolation, the finding of S. pneumoniae, N. meningitidis, H. influenzae and S. aureus as significant pathogens, usefulness of blood cultures in the detection of neonatal bacterial meningitis, increasing resistance of Gram-positive neonatal pathogens to cloxacillin, low CSF WBC, and the finding that the adjunctive use of dexamethasone significantly decreases case fatality and neurological sequelae.

Cerebrospinal Fluid Compartmental Pharmacokinetics of Amikacin in Neonates

To describe and investigate the covariate effects of cerebrospinal fluid (CSF) amikacin pharmacokinetics in neonates, CSF samples were prospectively collected from neonates in whom amikacin had been initiated before a diagnostic lumbar puncture was performed. CSF analysis (amikacin concentration, white blood count [WBC], glucose content, and protein concentration) and amikacin therapeutic drug monitoring results (peak and trough concentrations) in serum were recorded. Correlations (Spearman rank) between the CSF amikacin concentration and the CSF WBC and glucose and protein concentration were investigated. There were 44 CSF amikacin concentrations and 83 serum samples available from 43 neonates (mean postmenstrual age, 36 weeks [range, 26 to 41 weeks]; mean weight, 2.43 kg [range, 0.87 to 3.86 kg]). The median time interval between initiation of amikacin administration and CSF sampling was 25 h (range, 2.5 to 93.7 h). The median amikacin concentration in the CSF was 1.08 mg/liter (range, 0.34 to 2.65 mg/liter), and the mean trough and peak amikacin concentrations in serum were 3.8 +/- 2.5 mg/liter and 35.7 +/- 5.9 mg/liter, respectively. A correlation between CSF amikacin and CSF protein contents (P < 0.01, r = 0.41, 95% confidence interval = 0.13 to 0.63) but not between CSF WBC and CSF glucose was documented. A two-compartment (central and CSF) linear disposition model was used to estimate population pharmacokinetics. The half time for equilibration (T(eq)) between serum and CSF compartments was used as a measure of blood-brain barrier permeability. The T(eq) was 7.58 h (coefficient of variation [CV] = 49.1%) with a partition coefficient of 0.103 (CV = 26.4%). There was no relationship between the T(eq) and CSF WBC, CSF glucose content, or CSF protein content.

Neonatal Meningitis: What Is the Correlation Among Cerebrospinal Fluid Cultures, Blood Cultures, and Cerebrospinal Fluid Parameters?

Meningitis is a substantial cause of morbidity and mortality in neonates. Clinicians frequently use the presence of positive blood cultures to determine whether neonates should undergo lumbar puncture. Abnormal cerebrospinal fluid (CSF) parameters are often used to predict neonatal meningitis and determine length and type of antibiotic therapy in neonates with a positive blood culture and negative CSF culture. We evaluated the first lumbar puncture of 9111 neonates at > or =34 weeks' estimated gestational age from 150 NICUs, managed by the Pediatrix Medical Group, Inc. CSF culture results were compared with results of blood cultures and CSF parameters (white blood cells [WBCs], glucose, and protein) to establish the concordance of these values in culture-proven meningitis. CSF cultures positive for coagulase-negative staphylococci and other probable contaminants, as well as fungal and viral pathogens, were excluded from analyses. Meningitis was confirmed by culture in 95 (1.0%) neonates. Of the 95 patients with meningitis, 92 had a documented blood culture. Only 57 (62%) of 92 patients had a concomitant-positive blood culture; 35 (38%) of 92 had a negative blood culture. In neonates with both positive blood and CSF cultures, the organisms isolated were discordant in 2 (3.5%) of 57 cases. In each case, the CSF pathogen required different antimicrobial therapy than the blood pathogen. For culture-proven meningitis, CSF WBC counts of >0 cells per mm3 had sensitivity at 97% and specificity at 11%. CSF WBC counts of >21 cells per mm3 had sensitivity at 79% and specificity at 81%. Culture-proven meningitis was not diagnosed accurately by CSF glucose or by protein. Neonatal meningitis frequently occurs in the absence of bacteremia and in the presence of normal CSF parameters. No single CSF value can reliably exclude the presence of meningitis in neonates. The CSF culture is critical to establishing the diagnosis of neonatal meningitis.

Practice patterns and management of aseptic meningitis in a pediatric emergency department

Study objectives: Data describing the pediatric emergency department (ED) practice patterns and management in aseptic meningitis are limited. We evaluate use of diagnostic tests, antibiotic use, and ED disposition in an urban pediatric ED. Methods: This was a retrospective review of patients with an International Classification of Diseases, Ninth Revision discharge diagnosis of aseptic meningitis during January 1, 1996, and December 31, 2000, in an urban pediatric teaching hospital. Results: Sample size was 131 cases (56% male patients). More than 75% of patients presented during August to October. Seventy-two percent of patients presented complaining of 1 or more of the following symptoms; fever, stiff neck, headache, or vomiting, and average duration of symptoms before presentation was 48 hours. Classic examination findings of meningeal irritation were found in less than 16% of patients. Cranial computed tomography (CT) was ordered in 21% of suspected meningitis cases with normal level of consciousness, and no abnormalities were found. Median circulating WBC count was 10,800 cells/mL. Median cerebrospinal fluid WBC count was 345 cells/mL. The most common antibiotic administered was Ceftriaxone (63%). Rapid antigen tests were used in only 53% of children. Enteroviral polymerase chain reaction was used in only 53% of cases. Herpes virus polymerase chain reaction was ordered in 6 cases, and 1 length of stay was 3 days. Thirty-three percent of patients were admitted to the general medical floor, and 23.5% were sent home from the ED. Seventy-nine percent of patients were continued on Ceftriaxone as an inpatient until cerebrospinal fluid studies were completed. Ninety percent of patients were discharged without antibiotics. Conclusion: Aseptic meningitis has a benign presentation, and use of lumbar puncture may account for seasonal preponderance. Use of cranial CT is limited but appropriately so. Rapid adjunct diagnostic tests are ordered infrequently. New strategies to standardize ED care and reduce unnecessary laboratory tests are needed.

Utility of the peripheral blood white blood cell count for identifying sick young infants who need lumbar puncture

Study objective: We assess the utility of the peripheral blood WBC count as a screen for lumbar puncture among young infants evaluated for serious bacterial infections. Methods: We performed logistic regression modeling and receiver operating characteristic curve analysis of peripheral blood WBC count and cerebrospinal fluid WBC count for results obtained from 3- to 89-day-old infants undergoing a full sepsis evaluation. Results: Twenty-two of 5,353 (4.1 per 1,000) infants had acute bacterial meningitis. For diagnosing acute bacterial meningitis, the peripheral blood WBC count was poorly discriminating and significantly inferior to the cerebrospinal fluid WBC count. This was true both when the odds of meningitis were modeled to vary linearly and as a U-shaped function of the peripheral blood WBC count. When relying on single and interval-based high-risk thresholds of peripheral blood WBC counts alone, the majority of infants with acute bacterial meningitis would have been missed. Conclusion: Decisions to perform or withhold lumbar puncture should not be based on prevailing interpretations of the total peripheral blood WBC counts to maximize detection of bacterial meningitis in young infants. [Ann Emerg Med. 2003;41:206-214.]