Negative Cerebrospinal Fluid Cultures Research Articles

Mortality in adult patients with culture-positive and culture-negative meningitis in the Botswana national meningitis survey: a prevalent cohort study

SummaryBackgroundCNS infections are a leading cause of HIV-related deaths in sub-Saharan Africa, but causes and outcomes are poorly defined. We aimed to determine mortality and predictors of mortality in adults evaluated for meningitis in Botswana, which has an estimated 23% HIV prevalence among adults.MethodsIn this prevalent cohort study, patient records from 2004–15 were sampled from the Botswana national meningitis survey, a nationwide audit of all cerebrospinal fluid (CSF) laboratory records from patients receiving a lumbar puncture for evaluation of meningitis. Data from all patients with culture-confirmed pneumococcal and tuberculous meningitis, and all patients with culture-negative meningitis with CSF white cell count (WCC) above 20 cells per μL were included in our analyses, in addition to a random selection of patients with culture-negative CSF and CSF WCC of up to 20 cells per μL. We used patient national identification numbers to link CSF laboratory records from the national meningitis survey to patient vital registry and HIV databases. Univariable and multivariable Cox proportional hazards models were used to evaluate clinical and laboratory predictors of mortality.FindingsWe included data from 238 patients with culture-confirmed pneumococcal meningitis, 48 with culture-confirmed tuberculous meningitis, and 2900 with culture-negative CSF (including 1691 with CSF WCC of up to 20 cells per μL and 1209 with CSF WCC above 20 cells per μL). Median age was 37 years (IQR 31–46), 1605 (50%) of 3184 patients were male, 2188 (72%) of 3023 patients with registry linkage had documentation of HIV infection, and median CD4 count was 139 cells per μL (IQR 63–271). 10-week and 1-year mortality was 47% (112 of 238) and 49% (117 of 238) for pneumococcal meningitis, 46% (22 of 48) and 56% (27 of 48) for tuberculous meningitis, and 41% (1181 of 2900) and 49% (1408 of 2900) for culture-negative patients. When the analysis of patients with culture-negative CSF was restricted to those with known HIV infection, WCC (0–20 cells per μL vs >20 cells per μL) was not predictive of mortality (average hazard ratio 0·93, 95% CI 0·80–1·09).InterpretationMortality from pneumococcal, tuberculous, and culture-negative meningitis was high in this setting of high HIV prevalence. There is an urgent need for improved access to diagnostics, to better define aetiologies and develop novel diagnostic tools and treatment algorithms.FundingNational Institutes of Health, President's Emergency Plan for AIDS Relief, National Institute for Health Research.

Validation and Retrospective Clinical Evaluation of a Quantitative 16S rRNA Gene Metagenomic Sequencing Assay for Bacterial Pathogen Detection in Body Fluids

Next-generation sequencing-based 16S rRNA gene metagenomic sequencing (16S MG) technology has tremendous potential for improving diagnosis of bacterial infections given its quantitative capability and culture-independent approach. We validated and used a quantitative 16S MG assay to identify and quantify bacterial species in clinical samples from a wide spectrum of infections, including meningitis, septic arthritis, brain abscess, intra-abdominal abscess, soft tissue abscess, and pneumonia. Twenty clinical samples were tested, and 16S MG identified a total of 34 species, compared with 22 species and three descriptive findings identified by culture. 16S MG results matched culture results in 75% (15/20) of the samples but detected at least one more species in five samples, including one culture-negative cerebrospinal fluid sample that was found to contain Streptococcus intermedius. Shotgun metagenomic sequencing verified the presence of all additional species. The 16S MG assay is highly sensitive, with alimit of detection of 10 to 100 colony-forming units/mL. Other performance characteristics, including linearity, precision, and specificity, all met the requirements for a clinical test. This assay showed theadvantages of accurate identification and quantification of bacteria in culture-negative and polymicrobial infections for which conventional microbiology methods are limited. It also showed promises to serve unmet clinical needs for solving difficult infectious diseases cases.

Acetazolamide-Induced Aseptic Meningitis in a Female Adolescent with Idiopathic Intracranial Hypertension: A Case Report

AbstractDrug-induced aseptic meningitis (DIAM) has been documented for many years and is considered a diagnostic and patient management challenge. Associated medications include nonsteroidal anti-inflammatory drugs, antibiotics, and monoclonal antibodies, but no cases associated with acetazolamide have been reported. We briefly review a case of a 15-year-old female patient with history of idiopathic intracranial hypertension whose symptoms of aseptic meningitis associated with the use and increase of acetazolamide. DIAM should be considered a possibility in any patient with meningeal symptoms, pleocytosis, and negative cerebrospinal fluid culture. This is the first known case linking acetazolamide to DIAM.

Validation of multiplex PCR for the diagnosis of acute bacterial meningitis in culture negative cerebrospinal fluid.

This study evaluated the operational characteristics of the multiplex polymerase chain reaction (PCR) for cerebrospinal fluid (CSF) from patients with cellular and biochemical characteristics of acute bacterial meningitis and positive or negative CSF cultures. Multiplex PCR was performed for 36 CSF samples: culture-proven acute bacterial meningitis (n = 7), culture-negative acute bacterial meningitis (n = 17), lymphocytic meningitis (n = 8), and normal CSF (n = 4). The operational characteristics of multiplex PCR were evaluated with definite and probable bacterial meningitis, using culture positive, cytological and biochemical CSF characteristics as the gold standard. Multiplex PCR for CSF was efficient in the group with CSF cellular and biochemical characteristics of acute bacterial meningitis but with a negative CSF culture. This group demonstrated high specificity, positive predictive value, and efficiency. Multiplex PCR for CSF can improve the speed and accuracy of acute bacterial meningitis diagnosis in a clinical setting as a complement to classical immunological and bacteriological assays in CSF. It is also useful for CSF culture-negative acute bacterial meningitis.

Treatment of severe ventriculitis caused by extensively drug-resistant Acinetobacter baumannii by intraventricular lavage and administration of colistin.

BackgroundSevere ventriculitis (SV) caused by multidrug-resistant bacteria is associated with high morbidity and mortality in neurosurgical patients. This study assessed the outcomes of patients with SV caused by Acinetobacter baumannii who were treated by intraventricular (IVT) lavage and colistin administration.MethodsThis retrospective study included consecutive patients with SV caused by A. baumannii who were admitted at the Neurosurgical Department of Shanghai Tenth People’s Hospital from January 2014 to September 2017. Patients’ medical records, radiographic images, and surgical notes were reviewed. The patients were followed up for at least 6 months after discharge.ResultsA total of 25 patients, including 20 male and five female, were enrolled in this study; the average age was 45.6 years. All patients underwent neurosurgery before infection, and all A. baumannii cultures from cerebrospinal fluid (CSF) showed extensive resistance to the tested antibiotics except for tigecycline and colistin. All the patients underwent IVT lavage followed by daily administration of colistin after surgery; 24 patients received a daily colistin dose of 100,000 IU, while one received 50,000 IU. The patients also received tigecycline-based systemic antibiotic treatment. The mean duration of IVT colistin was 13.4±2.8 days. The time required to obtain a negative CSF culture was 8.9±4.0 days. Of the 20 patients who were cured, eight underwent shunt surgery due to hydrocephalus before they were discharged to a rehabilitation center. Five patients died, including one who was re-admitted due to recurrence 1 month after discharge.ConclusionsIVT lavage and colistin treatment may be an effective treatment for SV caused by extensively drug-resistant A. baumannii. Future studies with a larger sample size may be needed to verify the findings in this study.

The use of broad-range bacterial PCR in the diagnosis of infectious diseases: a prospective cohort study

ObjectivesBroad-range PCR has the potential to detect virtually any bacterial species via amplification and nucleotide sequencing of a DNA region common to all bacteria. We aimed to evaluate its usefulness and clinical relevance when applied to a wide variety of primary sterile materials. MethodsA prospective study including 1370 samples (75 heart valves, 151 joint tissue samples, 230 joint aspirates, 848 whole blood samples and 66 culture-negative cerebrospinal fluid samples) were studied by using a commercial PCR system for detecting 16S rDNA (Molzym). The PCR results were compared with culture and were considered to provide added diagnostic value only if the PCR approach revealed new pathogens that were missed by culture. ResultsThe added value of PCR was evident in 173 of 555 PCR-positive samples (0.126; 0.109–0.144 (proportion from all tested samples; 95% confidence interval)), most frequently in examinations of heart valves (0.56; 0.448–0.672) and joint tissue samples (0.219; 0.153–0.284). In contrast, the lowest rate of PCR with added value was noted for blood samples, regardless of the patient cohort they had been drawn from (nononcologic patients from intensive care: 0.065; 0.043–0.087, haematooncologic children: 0.048; 0.027–0.070). Moreover, PCR missed up to 7.1% of blood culture findings (0.071; 0.048–0.095) regarded as clinically relevant, which was the second highest failure rate after joint tissue samples (0.099; 0.052–0.147). ConclusionsBroad-range PCR substantially increases detection rate of pathogens, especially from heart valves and joint samples. However, a concurrent risk of false-negative PCR results justifies the need for parallel culture.

Duration of empirical therapy in neonatal bacterial meningitis with third generation cephalosporin: a multicenter retrospective study.

IntroductionThe duration of treatment is not well established, especially in the negative cerebrospinal fluid (CSF) culture. The aim of this study is to explore the influence of duration of treatment in neonatal bacterial meningitis.Material and methodsThis is a retrospective analysis of 200 CSF specimens. Two hundred full-term neonates with bacterial meningitis admitted to the clinical status were evaluated using the Glasgow Outcome Scale (GOS) on the day of discharge.ResultsNeonates were identified as having bacterial meningitis based on the results of CSF culture tests of all suspected cases. According to the GOS, neonates were divided into two outcome groups: 77.5% good (GOS = 5) (shorter than 3 weeks’ administration) and 22.5% unfavorable (GOS = 1–4) (longer than 3 weeks’ administration). The duration of antibiotic treatment ranged from 4 to 43 days, and the mean therapy time was 19.74 ±7.32 days. Duration longer than 3 weeks for neonatal bacterial meningitis with negative CSF culture had no impact on prognosis. The unfavorable outcome group had more prenatal infections and premature rupture of membranes cases than the good outcome group. High CSF protein and CSF glucose and CSF cell count increase were associated with unfavorable outcome in 167 non-prenatal infection infants. High CSF cell count increase was associated with unfavorable outcome in 33 prenatal infection infants. In term infants, the positive rate of blood cultures was 24.5%.ConclusionsThird generation cephalosporin therapy does not have a different prognosis for negative CSF culture of neonatal bacterial meningitis in term infants in this study.

Shunt Nephritis: An Increasingly Unfamiliar Diagnosis.

Shunt nephritis is a rare, reversible immune-complex mediated complication of cerebrospinal fluid (CSF) shunt infection that can progress to end-stage renal disease and even death if diagnosis is delayed. The present case report details the manifestation and clinical course of shunt nephritis in a 50-year-old patient who presented with symptoms of nephrotic syndrome 30 years after ventriculojugular shunt placement. Diagnosis was delayed due to initial negative CSF and blood cultures, but a later CSF culture was positive for Propionibacterium acnes. After treatment with intravenous antibiotics and complete removal of shunt with subsequent replacement with a new ventriculoperitoneal shunt, the nephritic symptoms resolved, but the patient continued to have reduced kidney function consistent with stage IIIa chronic kidney disease. This case emphasizes the clinical importance of having a high index of suspicion in patients with a ventricular shunt who present with symptoms consistent with nephritis, even in the setting of negative cultures and delayed presentation.

Shunt tapping versus lumbar puncture for evaluating cerebrospinal fluid infections in pediatric population.

To compare the results of lumbar puncture (LP) and shunt tapping in pediatric patients with suspected ventriculoperitoneal shunt infection. Medical records of pediatric patients with suspected shunt infections were retrospectively analyzed. All patients had cerebrospinal fluid samples obtained either via shunt tapping, LP or both. The diagnosis of infection was made when at least one cerebrospinal fluid had positive culture results. The patients with negative cerebrospinal fluid culture results were followed up for at least 6 months to monitor the occurrence of central nervous system infection. There were 20 patients in the study (12 males, 8 females). Cerebrospinal fluid was obtained by shunt tapping in 11, by lumbar puncture in 9 and by both methods in one patient. Thirteen patients [ Shunt tapping: 5/11 (45%), LP: 7/9 (78%), Both: 1) ] were diagnosed with shunt infection on the basis of cerebrospinal fluid culture. Seven patients with negative cerebrospinal fluid culture were found to have infections unrelated to shunts and did not show evidence of cerebrospinal fluid infection during the follow-up period. Although the percentage of detecting the infection was higher in LP group, both groups showed negative predictive value of 100%. Both shunt tapping and LP are effective in establishing the diagnosis of shunt infection in suspected patients.

Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.

Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections. We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed by PCR/Mass. Results were compared to real-time PCR detection. These four targeting pathogens could be discriminated without cross-reaction by the accurate detection of the corresponding extension products with different masses. The limits of detection were 102 copies/reaction for S. pneumoniae, H. influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of the culture-positive CSF specimens from the meningitis patients provided an overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was also able to detect the targeting pathogens from culture-negative CSF specimens from meningitis patients receiving early antibiotic treatment. PCR-Mass could be used for the molecular detection of bacterial meningitis and tuberculosis, especially when early antibiotic treatment has been administered to the suspected patients.

Diagnostic accuracy of CSF cell index and corrected CSF white blood cell count in healthcare-associated ventriculitis and meningitis after intracranial hemorrhage

Abstract Background The diagnosis of healthcare-associated meningitis and ventriculitis (HCAMV) in patients with intracranial hemorrhage (ICH) is challenging. The purpose of this study was to evaluate the diagnostic accuracy of routine cerebrospinal fluid (CSF) studies including a cell index and a corrected white blood cell (WBC) count. Methods Case control study of adult patients with the diagnosis of ICH and HCAMV at a large tertiary care hospital in Houston, Texas from 2003 to 2016. Cases were defined as patients with ICH and HCAMV as documented by a positive CSF culture. Controls were selected as patients with ICH without evidence of HCAMV, no previous antibiotic therapy and a negative CSF culture. Cases and controls were matched 1:2 by age, Glasgow Coma Scale (GCS) and Apache II scores. Cell index was calculated using the following formula: (CSF leukocytes / CSF erythrocytes) / (blood leukocytes / blood erythrocytes). Corrected WBC count was calculated using the following formula: CSF leukocytes - (CSF erythrocytes/1,000). Area under the curve of receiver operating characteristic (AUC-ROC) and 95% confidence interval (CI) for CSF cell index greater than or equal to absolute value of 1, corrected CSF WBC count greater than 5 K/uL, CSF lactate greater than 4 mmol/L, and CSF glucose less than 40 mmol/L, respectively, were calculated in order to determine the accuracy of these studies. Results A total of 120 patients with ICH were included in this study; 40 patients had proven HCAMV whereas 80 patients had ICH with no evidence of HCAMV. Matching of cases and controls by age, GCS, and Apache II score was appropriate (p>0.05). The AUC-ROC values for CSF cell index, corrected CSF WBC count, CSF lactate, and CSF glucose were all low at 0.609 (95% CI = 0.449–0.768), 0.731 (95% CI = 0.589–0.872), 0.719 (95% CI = 0.573–0.864), and 0.609 (95% CI = 0.449–0.768), respectively. Conclusion This study demonstrated poor accuracy of CSF cell index, corrected CSF WBC count, CSF lactate, and CSF glucose in diagnosis of HCAMV after ICH. Disclosures R. Hasbun, Biomeriaux: Consultant, Consulting fee. Biofire: Speaker’s Bureau, Speaker honorarium. Merck: Speaker’s Bureau, Speaker honorarium. Pfizer: Speaker’s Bureau, Speaker honorarium. Medicine’s Co: Speaker’s Bureau, Speaker honorarium.

Cerebrospinal Fluid Level of Glutamic Acid Decarboxylase (GAD) Antibody in Patients with Encephalitis

Background: Assaying the Glutamic Acid Decarboxylas( GAD) antibody in patients with encephalitis in cerebrospinal fluid and blood serum and its role in autoimmune encephalitis in children. Objective: This study Aimed at screening for GAD antibody in CSF of children presenting with acute encephalitis with non bacterial cause mostly autoimmune.Participants and methods: study is a pilot prospective study, conducted in the Pediatric department, Children’s Hospital, Ain Shams University.Fifty patients diagnosed with encephalitis exhibited at least one sign of parenchymatous brain dysfunction such as altered consciousness personality or behavior change, seizure, paresis, or ataxia. Encephalitis was defined as the presence of encephalopathy plus at least two of four findings: (1) fever (body temperature>38C); (2) abnormal cerebrospinal fluid examination (pleocytosis>5 white blood cells/mL and/or increased protein content>40 mg/dL) with negative cerebrospinal fluid culture; (3) abnormal electroencephalography findings compatible with encephalitis such as diffuse or focal slow activity, or periodic lateralized epileptiform discharges; and (4)abnormal results of neuroimaging, including computed tomography and magnetic resonance imaging (10), ,with age ranged from 6-144 Months; followed up In the period from September 2014 till March 2016.Basic clinical evaluation and laboratory investigations were done, GAD antibody level was measured in CSF and blood serum. Results: GAD receptor antibody titer was done in CSF which range from (36 -368 ng/l) with median of 64.83 (57.93-74.48), while in serum it range from (42.76-900) ng/l) with median 89.5(58.62-154.5).It was found that 6/50 (12%) patients had high GAD receptor antibody titer were high in CSF. The other 44/50 (88%) patients had low GAD antibody titer. In serum samples of twinty patients we had 8/20 (40%) patients had high GAD antibody titer and the rest were low GAD antibody titer 12/20 (60%).Significant occurrence of DCL, hospitalization plus mechanical ventilation and long term sequel were detected in patients with high GAD antibody titer. EEG findings; Two patients showed generalized epileptogenic activity, one patient had diffuse cortical dysfunction and two patient had multifocal epileptiform discharge and the rest of patients had normal finding. Eighty six precent had normal MRI findings,While 7 patients (14%) had non specific findings;3 patients had transient cortical meningeal enhancment,2 patients had high intensity in medial temporal lobe,one had abnormal signal intensity in medial temporal lobe and one patient had global brain atrophy. Conclusion: GAD Abs are directed against an intracellular antigen. The proposed pathogenic mechanisms of neurological disease in patients with antibodies directed against intracellular proteins is not clear. The present study emphasizes the importance of studying the CSF of patients with encephalitis suspected to be mediated by GAD autoimmunity.Both serum and CSF level must be assessed simultaneously as CSF level may change rapidly with fluctuation of disease. There are great efforts to be done to define the role of these GAD antibodies and to determine how they affect central nervous system function. These studies must be carried out so that appropriate treatments can be provided for the growing number of patients with possible antibody-mediated conditions.

Phenotypic Characterization and Serotypes Identification of CSF isolates in Acute Bacterial Meningitis

Background and Aim: Bacterial meningitis is a fatal disabling disease which needs prompt antibiotic management. As it causes a significant morbidity and mortality throughout the world, every developing country should have accurate information regarding the common etiological agents in bacterial meningitis cases. In the present study, we have serotyped the obtained agents in order to predict the usefulness of existing vaccines against bacterial meningitis. Materials and Methods: Two thousand nineteen cerebrospinal fluid (CSF) samples were obtained prospectively from suspected meningitis from January 2011 to July 2013 out of which 76 cases were approved by cytological, microbiological, molecular, and biochemical analysis as per the standard techniques. The isolated bacteria were serotyped to determine the predominant strain. Results: On the whole, 2019 CSF samples were collected, and bacterial etiology was isolated in 76 cases; S. pneumoniae in 31.5%, N. meningitides in 18.4%, and H. influenza in 10.5% of culture positive samples. Gram stained smears were positive in 63 samples. Among pneumococcal meningitis the most common serotype was 1, (29 %), followed by 19F, (25%), 18F, (8.3%), 6, (16.6%), 14, (12.5%), and 20 (8.3%). Out of the N. meningitidis positive CSF samples, 35.7%, 21.4%, and 35.7%, belonged to serogroups A, C, and W-135, respectively, and one non-groupable isolate were involved as S. pneumoniae meningitis. In the H. influenzae group only serotype b (87.5%), and untypable, 1, (7.5%) cases have been identified. Only 17, (0.8%) soluble antigens were detected from culture negative CSF samples. High protein and low sugar levels associated well with the features of ABM. The mean sugar and protein level in the CSF samples were 22.3 ± 9.8 mg/dl, 85.3 ± 51.29 mg/dl, respectively. Conclusions: The isolation rate of bacteria causing meningitis is 3.8%. Out of the total pneumococcal serotypes three of them were not included in the current vaccine in Ethiopia. Unusual findings and high a proportion of serogroup W-135 meningococci are observed in our study area The role of clinical presentations, routine CSF analysis in the rapid diagnosis of acute bacterial meningitis in cases of negative gram stained smears and a good knowledge of the bacterial epidemiology of meningitis can serve as a guide to start a rapid treatment as early as possible. Recommendation: the result of this study can be used to improve the existing vaccines to cover the detected serotypes and consequently reduce the incidence of bacterial meningitis.

Variability in Management of First Cerebrospinal Fluid Shunt Infection: A Prospective Multi-Institutional Observational Cohort Study

To describe the variation in approaches to surgical and antibiotic treatment for first cerebrospinal fluid (CSF) shunt infection and adherence to Infectious Diseases Society of America (IDSA) guidelines. We conducted a prospective cohort study of children undergoing treatment for first CSF infection at 7 Hydrocephalus Clinical Research Network hospitals from April 2008 through December 2012. Univariate analyses were performed to describe the study population. A total of 151 children underwent treatment for first CSF shunt-related infection. Most children had undergone initial CSF shunt placement before the age of 6 months (n = 98, 65%). Median time to infection after shunt surgery was 28 days (IQR 15-52 days). Surgical management was most often shunt removal with interim external ventricular drain placement, followed by new shunt insertion (n = 122, 81%). Median time from first negative CSF culture to final surgical procedure was 14 days (IQR 10-21 days). Median duration of intravenous (IV) antibiotic use duration was 19 days (IQR 12-28 days). For 84 infections addressed by IDSA guidelines, 7 (8%) met guidelines and 61 (73%) had longer duration of IV antibiotic use than recommended. Surgical treatment for infection frequently adheres to IDSA guidelines of shunt removal with external ventricular drain placement followed by new shunt insertion. However, duration of IV antibiotic use in CSF shunt infection treatment was consistently longer than recommended by the 2004 IDSA guidelines.

Identification of Common Bacterial Pathogens Causing Meningitis in Culture-Negative Cerebrospinal Fluid Samples Using Real-Time Polymerase Chain Reaction.

Background. Meningitis is a serious communicable disease with high morbidity and mortality rates. It is an endemic disease in Egypt caused mainly by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. In some settings, bacterial meningitis is documented depending mainly on positive cerebrospinal fluid (CSF) culture results or CSF positive latex agglutination test, missing the important role of prior antimicrobial intake which can yield negative culture and latex agglutination test results. This study aimed to utilize molecular technology in order to diagnose bacterial meningitis in culture-negative CSF samples. Materials and Methods. Forty culture-negative CSF samples from suspected cases of bacterial meningitis were examined by real-time polymerase chain reaction (real-time PCR) for the presence of lytA, bexA, and ctrA genes specific for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, respectively. Results. Positive real-time PCR results for Streptococcus pneumoniae were detected in 36 (90%) of culture-negative CSF samples while no positive results for Haemophilus influenzae or Neisseria meningitidis were detected. Four (10%) samples were negative by real-time PCR for all tested organisms. Conclusion. The use of molecular techniques as real-time PCR can provide a valuable addition to the proportion of diagnosed cases of bacterial meningitis especially in settings with high rates of culture-negative results.

Meningococcal Disease in Korea: an Epidemiologic Study of the Underestimated Infectious Disease.

Meningococcal Disease in Korea: an Epidemiologic Study of the Underestimated Infectious Disease.

Redefining true leukocytosis in the traumatic lumbar puncture

Objective: To compare and contrast the observed versus predicted number of white blood cells (WBCs) in a traumatic cerebrospinal fluid (CSF) sample in children and adults. Background: Clinicians rely on a correction formula (Predicted_CSF_WBC=CSF_RBC×Blood_WBC/Blood_RBC) to determine if a true CSF leukocytosis exists. This formula may overestimate true CSF leukocytosis and lead to delayed treatment of meningitis. Methods: A retrospective review of CSF data of 105 patients who met the following criteria: 1) CSF from lumbar puncture (LP) contained≥1000 RBC/mm^3 and 2) CBC performed≤24 hours of LP; 3) negative CSF cultures. Regression analysis was performed to determine the relationship between actual and predicted CSF WBC values. Results: Regression modeling indicated a discrepancy in the predicted versus actual WBC values. Mean adult age was 48.9 years; CSF profile (mean WBC 146.3×10^6/L; RBC 17374×10^6/L; glucose 4.1 mmol/L; protein 1.4 g/L); mean peripheral WBC was 8.2×10^9/L; RBC 3.9×10^9/L. Mean pediatric age was 1.4 years; CSF profile (mean WBC 171.8x10^6/L; RBC 41763x10^6/L; glucose 2.7 mmol/L; protein 1.7 g/L); mean peripheral WBC was 12×10^9/L; RBC 7.2×10^9/L. Observed LP CSF WBC value was 47% of predicted (r^2=0.54 pediatric cohort; r^2=0.91 adults). Conclusion: True CSF leukocytosis could be missed in a traumatic CSF sample based on a currently applied correction formula. We propose the following modifcation: Observed_CSF_WBC=0.5x[CSF_RBC×Blood_WBC/Blood_RBC].

Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study.

Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis. From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture. Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks. The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.

Early monitoring of ventriculostomy-related infections with procalcitonin in patients with ventricular drains

Several factors are implicated in the increased vulnerability of multiple trauma victims to infection, especially in intensive care units. The incidence of EVD related infections ranges from 5 to 20%. To assess the accuracy of serum procalcitonin (PCT) in predicting central nervous system (CNS) infection in patients with EVDs. Thirty-six adult patients with severe head trauma were enrolled in this prospective study, after exclusion of other causes of fever; patients were subjected to sampling of C-reactive protein (CRP), PCT, and cerebrospinal fluid (CSF) cultures every other day. Five patients developed ventriculostomy-related infections, and all had an elevated serum PCT concentration. Patients with negative CSF cultures had mean serum PCT <2.0 ng/ml, while patients with positive culture had early elevation of serum PCT with mean of 4.18 ng/ml, CRP did not show similar early changes. Patients who acquire CNS infection had prolonged length of stay in hospital and length of ventilation. In absence of other nosocomial infections, early high serum PCT concentrations appear to be a reliable indicator of bacterial CNS infection in patients with EVD.

Epidemiology of Meningitis Studied at a University Hospital in Zahedan, South-Eastern Iran

Background: Meningitis is an inflammation of the membranes, which surround the brain and spinal cord. Early treatment of bacterial meningitis can prevent serious complications. In the last two decades, three vaccines have been developed against the three main bacterial species implicated in meningitis of children in western countries and vaccine-preventable invasive bacterial meningitis has decreased substantially in the past few years. However, none of the developed vaccines are part of our childhood immunization schedule. Objectives: This study aimed to search the epidemiology of meningitis in Zahedan. Patients and Methods: In this cross–sectional survey, we studied all patients with meningitis for ten years, from May 2004 to May 2014, who had been referred to our hospital. The patients were evaluated according to their sex, age, clinical features, risk factors, pathogenic microorganisms, form of infection (acute or chronic) and clinical outcome. Results: Among the 53 patients with meningitis (47% females; 53% males with mean age 36 years) 47 cases (83%) had acute meningitis and six cases (17%) had chronic meningitis (four cases of tuberculosis and two cases of brucellosis). From the 47 cases with acute meningitis, only one case had a positive cerebrospinal fluid (CSF) culture for meningococci and 46 patients had negative CSF culture. The most common clinical symptoms was fever and headache (90%) and the least was seizure (9%). Mortality rate was 7.5% (4 cases). There were no significant risk factors except for two patients with acute meningitis and two cases with chronic meningitis. Conclusions: According to negative CSF cultures in acute meningitis, CSF culture using the BACTEC automated system and specific viral tests is recommended for detection of the etiological agents of viral and bacterial meningitis, particularly in the Iranian population where patients use antibiotics without prescription.