Negative Cerebrospinal Fluid Gram Research Articles

Aseptic Meningitis and Its Viral Etiologies, Clinical Characteristics and Management Practices in Children: A Retrospective Hospital-Based Study From Jordan.

PurposeIn this study, we aimed to describe the clinical characteristics, laboratory findings, aetiologies, and role of PCR in the decision on the management plan and duration of hospital stay in Jordanian children diagnosed with aseptic meningitis.MethodsThis retrospective observational cohort study included children diagnosed with meningitis who were admitted to the paediatric ward at Jordan University Hospital (JUH) during the period from January 2016 to August 2020. Patients were identified through the ICD9 discharge code of meningitis. Patients diagnosed with aseptic meningitis (defined as a patient with signs and symptoms of meningitis with a cerebrospinal fluid (CSF) white cell count of >5 cells/mm3, and a negative CSF Gram stain) were included, while patients who had low CSF glucose (<50% of serum) positive cerebrospinal fluid Gram stain and/or culture for bacterial meningitis were excluded.Files were reviewed to collect data on the clinical picture, viruses identified by the CSF viral polymerase chain reaction (PCR) panel, duration of medication, and hospital stay in patients with identified virus versus those with negative viral PCR.ResultsOne hundred and thirty-one patients were included: 87 males (66.4%) and 44 females (33.5%). Fever was the most common presenting symptom, followed by headache, vomiting, and excessive sleep in 48.0%, 42.7%, and 35.8% of the patients, respectively. Prior oral antibiotic use was reported in 48/125 (38.4%) patients.White blood cell count (WBC) ranged from 4.800 to 22.000. cells/mL, 45 patients (34.3%) had counts above 15.000 cells/mL. C-reactive protein level was high in 61/103 (59.2%) patients. CSF WBC count was <100 in 62 (47.3%) patients while neutrophils predominance of >70% was present in 27 (20.6%) patients. Viral panel PCR was done for 100/131 (76.3%) patients and was positive in 66/100 (66%) patients; with enterovirus being the most common identified viruses (60/100; 60%).The average duration of hospital stay was 5.9 and 5.5 days for those with negative and positive PCR respectively. Ten (7.6%) patients had seizures upon presentation. None of the patients had any neurological sequel related to his meningitis.ConclusionEnteroviruses are the most common identified cause of paediatric aseptic meningitis in Jordan. Although PCR revealed an identified virus in around half of the patients, nevertheless, there was no adjustment in the management plan regarding duration of empirical antibiotic use and hospital stay. Increasing knowledge and awareness among clinicians on viral meningitis’ lab characteristics might have great impact on duration of hospital stay and thus would be reflected on the patient and the healthcare system as well.

Risk Classification for Enteroviral Infection in Children With Meningitis and Negative Gram Stain.

Enterovirus is the most common cause of aseptic meningitis in children. This study aimed at identifying baseline variables associated with a positive cerebrospinal fluid (CSF) Enterovirus polymerase chain reaction (PCR) to aid clinicians in targeting patients who could be tested and treated as outpatients. We performed a retrospective review of children (2 months to 17 years old) admitted to the Children's Memorial Hermann Hospital in Houston, TX, between January 2005 and December 2010 with symptoms of meningitis, CSF white cell count of greater than 5 cells/mm, and a negative CSF Gram stain, who had a CSF Enterovirus PCR. One hundred thirty-seven children were reviewed; median age was 4.7 (0.1-17.1) years, and 79 (58%) were male. Fifty patients (37%) had positive CSF Enterovirus PCR. Only 13 (15%) of the Enterovirus PCR-negative patients had an identifiable etiology. All patients were hospitalized. The mean hospital stay for patients with Enterovirus was 2.9 days; 88% received empiric antibiotics. Rates of antibiotic administration were not different between PCR-positive and PCR-negative groups (P > 0.05). All patients with Enterovirus had a favorable clinical outcome.A predictive model was created using 3 baseline variables independently associated with a positive Enterovirus PCR (P < 0.05): May to November presentation, CSF protein of less than 100 mg/dL, and absence of focal neurologic signs. The model classified patients into 2 risk categories for a positive Enterovirus PCR (low risk, 0% [0/17 patients]; high risk, 42% [50/120 patients]; P < 0.001). Our predictive model can be used to identify children for whom Enterovirus PCR testing is warranted. Such testing could avoid unnecessary hospitalization and antibiotic administration.

Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections.

The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause

We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193) and a retrospective validation (n = 567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high (≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95% CI 93.9-100.0%) in the validation cohort and 100.0% (95% CI 97.8-100.0%) in bacterial meningitis patients. The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause.

Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

ObjectiveTo derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and MethodsWe conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. ResultsOf the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. ConclusionAdults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation.

Meta-analysis of bacterial meningitis score validation studies

ObjectiveThe Bacterial Meningitis Score, a derived and validated clinical decision rule, identifies children with cerebrospinal fluid (CSF) pleocytosis who are at very low risk of bacterial meningitis. Low-risk features include...

Acute Bacterial Meningitis in Adults: A 12-Year Review

One hundred three episodes of acute bacterial meningitis in adults hospitalized in Edmonton's 2 largest hospitals from 1985 to 1996 were reviewed. Cases complicating neurosurgery were excluded. Most cases were community-acquired (87%). Twenty-three cases remained culture-negative, and there was no statistical relation between culture negativity and antibiotic pretreatment. Streptococcus pneumoniae was the predominant pathogen (52.5%), but Listeria monocytogenes was the second most common isolate, accounting for 12.5% of culture-positive cases. Compared to non-listerial meningitis, those with listeriosis were more likely to have negative cerebrospinal fluid (CSF) Gram stains (p = 0.07), CSF leukocyte counts < 1,000 cells/mm3 (p < 0.003), and normal CSF glucose (p = 0.006). Bacterial antigen detection was found to be of low sensitivity: 33% in all patients, but only 9% in cases with negative CSF Gram stains. The overall mortality was 18%, with 15 deaths directly attributable to acute meningitis; the case-fatality rates for S. pneumoniae and L. monocytogenes were 24% and 40%, respectively. Mortality was significantly higher among those with seizures (34% versus 7%, respectively; p < 0.001; OR = 17.6). Despite the urgency of acute bacterial meningitis, there were considerable delays in the institution of empiric antibiotics; mortality rates were slightly higher in those who experienced such a delay (16% versus 7% respectively; p = 0.18).

Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis.

Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture. Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF. To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge. Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples. Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65. All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997. Total cost of hospitalization. A total of 126 infants were identified. One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October). Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission. Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days). Total cost of hospital care for all 126 infants was $381,145. In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively. Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would increase cost savings. A prospective study is needed to validate these results. Arch Pediatr Adolesc Med. 2000;154:817-821

Prospective validation of a diagnosis model as an aid to therapeutic decision-making in acute meningitis.

The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis, based on four parameters collected at the time of first lumbar tap: cerebrospinal fluid protein level, cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to therapeutic decision-making in 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. In each case pABM was computed before a therapeutic decision and three diagnoses were established successively: (i) clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral meningitis, or meningitis of undetermined origin); (ii) computation of pABM (viral meningitis if pABM< 0.1, bacterial meningitis otherwise); and (iii) determination of definitive diagnosis (bacterial meningitis: positive cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid culture, no other aetiology and no treatment; meningitis of undetermined origin: cases fitting neither of the first two diagnoses). The computed diagnosis was viral meningitis in 78 of the 80 cases diagnosed definitively as viral meningitis, and bacterial meningitis in four of the five cases diagnosed definitively as bacterial meningitis. Negative and positive predictive values and accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively as viral cases; in all of these 15 cases, the computed diagnosis was viral meningitis, leading the physician to refrain from starting antibiotics in all of them. The results confirm that the model evaluated is reliable and aids in the identification of patients in whom antibiotics can be safely avoided.

Acute meningitis with a negative gram's stain: Clinical and management outcomes in 171 episodes

purpose: To characterize the diagnostic spectrum and physician management decisions of patients presenting to an emergency department with an acute, community-acquired illness, cerebrospinal fluid (CSF) white blood cell count >5/mm 3, and a negative Gram's stain for bacteria. patients and methods: In this retrospective cohort study over a 2-year period, symptoms, examination findings, paraclinical data, physician management, and clinical outcomes were assessed for each patient. results: One hundred sixty-eight patients (171 patient episodes) were evaluated. Almost half of the cohort presented in nonsummer months (48%); 20% had concurrent comorbid disease, and 15% had identified immunocompromising conditions. The reported examination findings were diverse, with fever (49%) and neck stiffness (39%) being the most frequent findings. The majority were hospitalized (70%), with a median stay of 4 days. Approximately one half underwent computed tomography or magnetic resonance imaging (49%), and received empiric treatment with antibiotics (52%). A diagnostic cause was established in 23%, with the majority being inherently treatable diseases (including syphilis, bacteremia, Lyme disease). Variables significantly associated with a subsequent proven diagnostic cause included: age >60 years; presence of comorbid disease (especially immunodeficiency); and presentation in winter months. conclusions: A large proportion of patients presenting with acute meningitis and a negative CSF Gram's stain undergo hospitalization, noninvasive cranial imaging, and receive empiric antibiotic therapy. Better clinical guidelines are needed to identify the diagnostic and management decisions that benefit patient outcome.