Suspected CNS Infection Research Articles

Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study

Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. For the French and Portuguese translations of the abstract see Supplementary Materials section.

Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study

BackgroundThe early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM.MethodsWe prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment.ResultsThe concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (all P < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770–0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05).ConclusionsCSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.

S7.1d Reliability of bedside point-of-care tests for Candida neoformans , M. tuberculosis and S. pneumoniae in adults living with HIV presenting with suspected central nervous system infection (CNS) in low- and middle-income settings: Preliminary results from the DREAMM study

S7.1 Update in management of fungal infection in adult hematology, September 23, 2022, 10:30 AM - 12:00 PMBackgroundBedside point-of-care (POC) testing, with parallel laboratory testing, represents a unique opportunity to improve and speed up the diagnostic workup of people living with HIV with suspected CNS infection in resource-limited settings.ObjectivesTo assess the agreement between POC tests for Cryptococcus neoformans, Mycobacterium tuberculosis, and Streptococcus pneumoniae performed at the bedside and in the routine laboratory, in African low- and middle-income countries (LMICs).MethodsFrom January 2018 to March 2021, the following POC tests were performed in parallel at the bedside and in the routine laboratory: Cryptococcal antigen lateral flow assay (CrAg LFA, Immy) in blood and cerebrospinal fluid (CSF), tuberculosis lipoarabinomannan (TB-LAM, Alere) in urine, and, where indicated, pneumococcal antigen (Streptococcus pneumoniae (SP), Biosynex) in CSF.Participants: HIV-infected adults (>18 years old) suspected of CNS infection.Setting: The prospective multicenter DREAMM project (Driving Reduced AIDS Meningo-Encephalitis Mortality) in five hospital sites in Cameroon, Malawi, and Tanzania.Primary outcome: Cohen's kappa statistic of agreement between the results of POC tests obtained at the bedside and the routine laboratory.ResultsThe study included 356 consecutive participants (mean age 39.5 +/- 10 years; 68.7% ART-experienced; 46.3% male; median CD4 count 75/mm3; abnormal mental status 75%). In total, 148/355 (41.7%) participants had positive bedside CrAg in blood, 140/315 (44.4%) positive bedside CrAg in CSF, 64/339 (18.9%) positive bedside TB-LAM in urine, and 10/175 (5.7%) positive bedside SP in CSF. Kappa statistics evaluating agreement between bedside and laboratory test results were: 0.98 [95% confidence interval (CI) 0.96-1.00; n = 347] for blood CrAg, 0.99 (95%CI, 0.98-1.00; n = 307) for CSF CrAg, 0.92 (95% CI, 0.87-0.98; n = 330) for urinary TB-LAM, and 0.68 (95%CI, 0.40-0.96; n = 34) for CSF SP.ConclusionsBedside POC tests for Cryptococcus spp. are highly reliable and can be safely performed in parallel to laboratory testing to expedite targeted treatment in people living with HIV with suspected CNS infection in African LMICs. Other bedside POC tests need further evaluation before large-scale implementation.

FilmArray\xae Meningoencephalitis panel in the diagnosis of central nervous system infections: stewardship and cost analysis in a paediatric hospital in Chile

BackgroundCentral nervous system (CNS) infection has been an ongoing concern in paediatrics. The FilmArray® Meningoencephalitis (FAME) panel has greater sensitivity in identifying the aetiology of CNS infections. This study’s objective was to compare the aetiological identification and hospitalization costs among patients with suspected CNS infection before and after the use of FAME.MethodsAn analytical observational study was carried out using a retrospective cohort for the pre-intervention (pre-FAME use) period and a prospective cohort for the post-intervention (post-FAME use) period in children with suspected CNS infection.ResultsA total of 409 CSF samples were analysed, 297 pre-intervention and 112 post-intervention. In the pre-intervention period, a total of 85.5% of patients required hospitalization, and in the post-intervention period 92.7% required hospitalization (p < 0.05). Median of ICU days was significantly lower in the post-intervention period than it was in the pre-intervention period. The overall positivity was 9.4 and 26.8%, respectively (p < 0.001). At ages 6 months and below, we found an increase in overall positivity from 2.6 to 28.1%, along with an increased detection of viral agents, S. agalactiae, S. pneumoniae, and N. meningitidis. The use of this diagnostic technology saved between $2916 and $12,240 USD in the cost of ICU bed-days. FAME use provided the opportunity for more accurate aetiological diagnosis of the infections and thus the provision of adequate appropriate treatment.ConclusionsThe cost/benefit ratio between FAME cost and ICU bed-day cost savings is favourable. Implementation of FAME in Chilean public hospitals saves public resources and improves the accuracy of aetiological diagnosis.

Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection.

ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.ConclusionsFor patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.

Impact of cerebrospinal fluid syndromic testing in the management of children with suspected central nervous system infection.

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1year, with possible CNS infection and CSF pleocytosis (> 15cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10)days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10)days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

Cerebro spinal fluid pleocytosis: A clinicopathologic analysis

Background: Cerebro Spinal Fluid (CSF) examination is very useful in patients of suspected CNS disease and the necessity of correlating it with the clinico-pathologic findings which will help in early diagnosis of CNS diseases and guide the further management of the disease. CSF examination with quantification of leukocytes and differential count of cellular subsets in the cerebrospinal fluid is a standard procedure in cases of suspected infectious conditions. Present study emphasises pleocytosis in the cerebrospinal fluid along with other laboratory parameters. Materials and Methods: The study is consisting of 295 CSF samples from patients with clinically suspected CNS infections. The CSF findings were evaluated in all age group patients in relation to cell counts and pleocytosis. Results: In Physical examination of CSF colour, appearance and received quantity were evaluated. Maximum specimen was received in 1 year to 18 year age group. CSF pleocytosis (>5cells/µl) was present maximum (48%) in 1 month to less than 1 year age. Pleocytosis >5 leucocytes/µl was found in 121 (41%) samples out of 295 samples. Conclusion: CSF cell count examination is very common and useful investigation done for suspected various CNS diseases. Infectious and non-infectious diseases of CNS can cause pleocytosis of the cerebrospinal fluid. The type of cells depends mainly on the clinical scenario. However it seems to vary with total cell count also, such as lymphocytes predominating at lower total cell counts while neutrophils are at higher total counts.

New onset neurologic events in people with COVID-19 in 3 regions in China.

To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19). A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus. We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new-onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n = 25) or stroke (n = 10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions. Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor. Brain CT in 28 people led to new findings in 9. Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable. People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking.

Diagnostic Accuracy of Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin in Patients with Acute Bacterial Meningitis: A Prospective Cohort Study

Background: It is difficult for early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM).Therefore, a novel and reliable biomarker is urgently required. Neutrophil Gelatinase-Associated Lipocalin (NGAL) have been reported as a novel biomarker for differentiating the bacterial or viral infections, however, whether the CSF NGAL is a potential biomarker for distinguishing between BM and TBM or CM are not reported. Methods: Prospectively enrolled the patients with suspected CNS infections at admission, and divided them into three case groups: BM (n=47), TBM (n=34), CM (n=30), and a hospitalized control (HC, n=39). Detected the CSF NGAL and evaluate the diagnostic accuracy to distinguish between BM and TBM or CM. Meanwhile, longitudinally measured the CSF NGAL of BM to evaluate whether it would be a monitor of the antibacterial treatment. Results: The CSF NGAL in BM was significantly higher than TBM, CM and HC, and the serum NGAL was not significantly different among three case groups. The ROC analysis showed that CSF NGAL presented a good diagnostic performance with an AUC of 0.907(95% CI: 0.830 to 0.985), and at the optimal cutoff value of 16.55 ng/mL with 88.46% sensitivity and 81.25% specificity for discriminating BM from TBM or CM. Meanwhile, the CSF NGAL in convalescent period of BM was significantly lower than the acute period. Conclusion: CSF NGAL could be used as an early diagnostic biomarker of BM, especially when compared with TBM or CM, and it also might be have some important clinical value for monitoring antibiotic therapy of BM. Funding Statement: The study was supported in part by the grants from the National Natural Science Foundation of China (No.81802088), the Joint Funds for the innovation of science and Technology, Fujian Province (No.2018Y9080), the Natural Science Foundation of Fujian Province (No.2016J05185), and the Youth Foundation of Health and Family Planning Commission of Fujian Province (No.2016-1-55). Declaration of Interests: The authors: No reported conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Fujian Medical University. Written informed consent was obtained from the participants or their surrogates prior to the study.

A Study of the John Cunningham Virus (JCV) Seroprevalence among Zambian Adults presenting with “Meningoencephalitis” to the University Teaching Hospital, Lusaka, Zambia

Background:&#x0D; The John Cunningham virus (JCV) is an opportunistic virus which leads to the development of progressive multifocalleukoencephalopathy (PML), which is a lytic infection of oligodendrocytes of the central nervous system in immunosuppressed patients. Infection with the JCV occurs in childhood and the virus remains quiescent in the body, activating during immunosuppression. Exposure to the virus can be detected by testing for JC virus specific antibodies inan ELISA test. Our aim was to determine the JCV seroprevalence and factors associated with its positivity among Zambian adults presenting to the University Teaching Hospital (UTH) with suspected meningoencephalitis and to assess the JCV ELISA test as a possible tool for PML risk stratification.&#x0D; Methodology:&#x0D; This was a cross sectional nested study in the TB meningitis in Zambia (TMZ) study which looked at improving ways of TB diagnosis in patients with meningoencephalitis. It included adults 18 years and older who presented with suspected meningoencephalitis and had undergone a lumbar puncture as part of their evaluation. 50 HIV positive and 50 HIV negative patients were selected from the parent study and underwent testing for JCV serology. PML cases were also recruited from the parent study based on clinical features, confirmed by JCV DNA PCR of CSF.&#x0D; Results:&#x0D; Final analysis for JCV seroprevalence was done in 96 patients and noted to be 46% (95% CI, 35.62 – 56.31). The JCV seroprevalence in the HIV positive group was 40.82% and in the HIV negative group was 51.06 % but there was no statistical difference (p-value 0.31). None of the other factors studied had any impact on the JCV seroprevalencesuch as age, gender, clinical presentation, CD4 count and co-morbid TB meningitis (TBM) diagnosis. There was a bimodal distribution of age associated with JCV seropositivity; with one peak occurring in the 18 to 20 years age group and thesecond peak occurring in the 55 to 60 years age group. 14 (3.2%) confirmed PML cases, based on clinical features and JCV DNA CSF positive, were all JCV seropositive and HIV positive with advanced immunosuppression (CD4&lt;200/mm3).Memory impairment was associated with a 6 fold increased likelihood of having PML in advanced HIV disease with JCV seropositive patients which further, increased to over 20 fold after adjusting for age , gender and TBM diagnosis. After adjusting for other variables TBM was associated with an 87% less likelihood of having PML (p-value 0.03).Female gender was associated with increased risk of having PML (p-value 0.02) and a younger age was protective for PML (p-value 0.03).&#x0D; Conclusion:&#x0D; The prevalence of anti-JCV antibodies in patients with suspected CNS infection (meningoencephalitis) was 46%. Anti- JCVantibody prevalence did not differ significantly by age, gender, HIV status or CD4 count. Memory impairment in JCV seropositive, advanced HIV disease patients with meningoencephalitis was the most important variable associated with having PML.

HOUT-26. FACTORS ASSOCIATED WITH TREATMENT DELAY IN CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract OBJECTIVE To identify clinico-radiographic characteristics associated with delayed treatment initiation in central nervous system lymphoma (CNSL). INTRODUCTION Clinical and radiographic characteristics of CNSL are often varied with a broad differential diagnosis, potentially leading to delays in diagnosis and treatment. METHODS A single-center retrospective review of clinico-radiographic data was performed at Columbia University Irving Medical Center in patients with pathologically confirmed CNSL diagnosed from 1/2010–12/2018. Descriptive statistics and univariate logistic regression were used to identify variables associated with delayed treatment. Using visual binning, delayed treatment time was designated as &gt;33 days from first presentation to medical attention to first chemotherapy for CNSL. Variables of interest included demographic data, presenting symptomatology, radiographic characteristics, location of initial presentation, and diagnostic and therapeutic interventions performed before biopsy. RESULTS Seventy patients (36 men (51%); median age at diagnosis 70 years, IQR 14.75 years; median time from first presentation to treatment 21 days, IQR 41.25 days) were included. Presentation with cognitive deficits suggested a strong, but not statistically significant, association with delayed treatment (OR=1.93, p=0.20), whereas presentation with focal neurologic deficits suggested protection against delayed treatment (OR=0.25, p=0.05). Initial presentation to a hospital suggested a strong, but not statistically significant, trend against delayed treatment (OR=0.41, p=0.08). Multifocal disease on neuroimaging (OR=7.18, p=0.001), pre-biopsy cerebrospinal fluid (CSF) sampling (OR=5.18, p=0.002), and pre-biopsy immunomodulatory treatment (including high-dose intravenous corticosteroids) for suspected neuroinflammatory disease (OR=6.33, p=0.03) had statistically significant associations with delayed treatment. Antimicrobial treatment before biopsy for suspected CNS infection suggested a trend toward delayed treatment, but the association was not statistically significant (OR=5.1, p=0.06). CONCLUSIONS Multifocal disease and pre-biopsy CSF sampling and immunomodulatory therapy were associated with delayed treatment initiation for CNSL in our single-center cohort. Recognizing factors associated with delayed treatment may allow physicians to circumvent these factors and permit more rapid diagnosis through tissue sampling.

Early clinical management of acute CNS infections: a prospective cohort study.

Aim: To explore early management and clinical predictors of patients with suspected CNS infections. Methods: In a prospective cohort study of 125 adult patients with suspected CNS infections, clinical features and early management time points were compared between groups with and without confirmed CNS infections. Results: The door-to-lumbar puncture time was associated with the initial Glasgow Coma Scale score, the confirmed diagnosis and the time to change empirical treatment. Multivariate analysis indicated that the initial Glasgow Coma Scale score was an independent risk factor for prognosis. Conclusion: Lumbar puncture plays a crucial role in early management of CNS infections. Patients with CNS infection who have disturbances of consciousness should receive particular attention.

The utility of MRI in suspected CNS infection in patients with haematological malignancy – a retrospective ten-year review

Category: Neuro.

P: 20 EID-UL-AZHA (Muslim's Festival of Sacrifice): Increased Frequency of Spontaneous Encephalopathy, Whether This Is Secondary to Consumption of High Protein Diet?

BACKGROUND: Protein restricted diet once was the cornerstone of the management of Hepatic encephalopathy, latter no evidence showed significant benefits. However sub group of cirrhotics are intolerant to dietary proteins, especially animal proteins. We compared precipitants of encephalopathy and effect of animal proteins consumption during the festival of EID-UL-AZHA METHODS: A retrospective comparative cross sectional study was conducted and analyzed hospital data of AIMS (Asian institute of medical sciences, Hyderabad, Pak.). Patients of cirrhosis were enrolled with clinically diagnosed hepatic encephalopathy in two groups. Group A was categories with patients admitted 15 days before EID-Ul-AZHA and Group B includes patients admitted on EID UL AZHA day and up to 15 days afterward. Patients with neurological deficit and suspected CNS infection were excluded. Patient of both groups were assessed to compare precipitant factors for encephalopathy that includes infections, electrolytes imbalance, upper GI bleed, constipation, AKI and drugs. Dietary history regarding normal protein diet and high protein diet (animal proteins &gt; 1.5 g/kg/day) were also collected and compared in both groups. RESULTS: Out of 378 screened patients, 92 were presented with encephalopathy. All patients were Muslims with mean age 54.36 ± 11 yrs. Majority 66.3% were males and 33.7% were females. Precipitating factors were identified in 70.2% and 62.9% in group A and B respectively. Precipitating factor remain unidentified in 29.8% patients in group A and 37.1% in group B. 98.2% patients in group A were taking usual diet, only 1.8% consumed high (animal) protein diet, while in group B 51.4% patients were on usual diet and 48.6% consumed high (animal) protein diet. A comparable rise in frequency of spontaneous hepatic encephalopathy (without an identified precipitating factors) was observed in group B and 76.9% patients out of them were consuming high (animal) protein diet. CONCLUSIONS: A comparable rise in frequency spontaneous hepatic encephalopathy was observed during and/or post event of EID-UL-AZHA, majority had consumed high (animal) proteins. Consumption of meat (animal proteins) could be the possible contributing factor. Generally protein restriction is not recommended in cirrhotics but, still in sub group of cirrhotics who are protein intolerant, protein restriction or substitution of source of protein is inevitable. A further multicenter study is necessary at a larger scale to find out characteristic of patients who are intolerant to animal proteins.

CSF penetration of vancomycin in critical care patients with proven or suspected ventriculitis: a prospective observational study.

Vancomycin is recommended for ventriculitis. However, penetration into the CNS is relatively poor. To investigate the population pharmacokinetics of vancomycin in serum and CSF in critical care patients with proven or suspected CNS infections from neurosurgical procedures. This was an observational pharmacokinetic study in critical care patients with proven or suspected CNS infections receiving intravenous vancomycin. Multiple blood and intraventricular CSF samples were collected. Population pharmacokinetic analysis and simulation were undertaken with ADAPT5 and Pmetrics. A total of 187 blood and CSF samples were collected from 21 patients. The median (range) Cmax and Cmin concentrations in serum were 25.67 (10.60-50.78) and 9.60 (4.46-23.56) mg/L, respectively, with a median daily dose of 2500 (500-4000) mg. The corresponding median concentrations in CSF were 0.65 (<0.24-3.83) mg/L and 0.58 (<0.24-3.95) mg/L, respectively. The median AUC0-24 in serum and CSF was 455.09 and 14.10 mg·h/L, respectively. A three-compartment linear population pharmacokinetic model best fitted the observed data. Vancomycin demonstrated poor penetration into CSF, with a median CSF/serum ratio of 3% and high intersubject pharmacokinetic variability of its penetration. Therapeutic drug monitoring in both serum and CSF and higher daily doses may be an option to ensure adequate trough levels and to optimize patient therapy. Novel dosing strategies designed to reduce renal toxicity, such as administration by continuous infusion, should be investigated in further clinical studies to avoid antibiotic underexposure in CSF.

Presentation, etiology, and outcome of brain infections in an Indonesian hospital

Little detailed knowledge is available regarding the etiology and outcome of CNS infection, particularly in HIV-infected individuals, in low-resource settings. From January 2015 to April 2016, we prospectively included all adults with suspected CNS infection in a referral hospital in Jakarta, Indonesia. Systematic screening included HIV testing, CSF examination, and neuroimaging. A total of 274 patients with suspected CNS infection (median age 26 years) presented after a median of 14 days with headache (77%), fever (78%), seizures (27%), or loss of consciousness (71%). HIV coinfection was common (54%), mostly newly diagnosed (30%) and advanced (median CD4 cell count 30/µL). Diagnosis was established in 167 participants (65%), including definite tuberculous meningitis (TBM) (n = 44), probable TBM (n = 48), cerebral toxoplasmosis (n = 48), cryptococcal meningitis (n = 14), herpes simplex virus/varicella-zoster virus/cytomegalovirus encephalitis (n = 10), cerebral lymphoma (n = 1), neurosyphilis (n = 1), and mucormycosis (n = 1). In-hospital mortality was 32%; 6-month mortality was 57%. The remaining survivors had either moderate or severe disability (36%) according to Glasgow Outcome Scale. In this setting, patients with CNS infections present late with severe disease and often associated with advanced HIV infection. Tuberculosis, toxoplasmosis, and cryptococcosis are common. High mortality and long-term morbidity underline the need for service improvements and further study.

The aetiologies of central nervous system infections in hospitalised Cambodian children

BackgroundCentral nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.MethodsWe did a one year prospective study of children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens.ResultsBetween 1st October 2014 and 30th September 2015, 284 analysable patients were enrolled. The median patient age was 2.6 years; 62.0% were aged <5 years. CSF white blood cell count was ≥10 cells/μL in 116/272 (42.6%) cases. CNS infection was microbiologically confirmed in 55 children (19.3%). Enteroviruses (21/55), Japanese encephalitis virus (17/55), and Streptococcus pneumoniae (7/55) accounted for 45 (81.8%) of all pathogens identified. Of the pathogens detected, 74.5% (41/55) were viruses and 23.6% (13/55) were bacteria. The majority of patients were treated with ceftriaxone empirically. The case fatality rate was 2.5%.ConclusionsEnteroviruses, JEV and S. pneumoniae are the most frequently detected causes of CNS infection in hospitalised Cambodian children.

Use of multiplex PCR based molecular diagnostics in diagnosis of suspected CNS infections in tertiary care setting—A retrospective study

ObjectivesCNS infections like meningitis and encephalitis pose enormous healthcare challenges due to mortality, sequelae and socioeconomic burden. In tertiary setting, clinical, microbiological, cytological and radiological investigations are not distinctive enough for diagnosing microbial etiology. Molecular diagnostics is filling this gap. We evaluated the clinical impact of a commercially available multiplex molecular diagnostic system − SES for diagnosing suspected CNS infections. Patients and methodsThis study was conducted in our tertiary level Neurology ICU. 110 patients admitted during Nov-2010 to April-2014 were included. CSF samples of patients clinically suspected of having CNS infections were subjected to routine investigation in our laboratory and SES test at XCyton Diagnostics. We studied the impact of SES in diagnosis of CNS infections and its efficacy in helping therapeutic management. ResultsSES showed detection rate of 42.18% and clinical specificity of 100%. It had 10 times higher detection rate than conventional tests. Streptococcus pneumoniae and Mycobacterium tuberculosis were two top bacterial pathogens. VZV was most detected viral pathogen. SES results elicited changes in therapy in both positive and negative cases. We observed superior patient outcomes as measured by GCS scale. 75% and 82.14% of the patients positive and negative on SES respectively, recovered fully. ConclusionDetecting causative organism and ruling out infectious etiology remain the most critical aspect for management and prognosis of patients with suspected CNS infections. In this study, we observed higher detection rate of pathogens, target specific escalation and evidence based de-escalation of antimicrobials using SES. Institution of appropriate therapy helped reduce unnecessary use of antimicrobials.

Clinical Features of Suspected CNS Infection in A Tertiary Care Center

Clinical Features of Suspected CNS Infection in A Tertiary Care Center

Performing lumbar punctures for suspected CNS infections: experience and practice of trainee doctors.

Lumbar punctures are essential in the management of suspected CNS infections. However, despite clear guidelines their use can be haphazard. This survey investigated the training, knowledge and experience of UK doctors in training in relation to lumbar punctures.