scholarly journals Clinical Application and Drug-Use-Guidance Value of Metagenomic Next-Generation Sequencing in Central Nervous System Infection

2021 ◽  
Author(s):  
Ke Lin ◽  
Hao-Cheng Zhang ◽  
Yi Zhang ◽  
Yang Zhou ◽  
Zhang-Fan Fu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Use ◽  
Clinical Application ◽  
Bacterial Infections ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Cns Infections ◽  
Grade 3 ◽  
The Impact

Abstract Background Timely and precise etiology diagnosis is crucial for optimized medication regimens and better prognosis in central nervous system infections (CNS infections). We aimed to analyze the impact of mNGS tests on the management of patients with CNS infections. Methods We conducted a single-center retrospective cohort study to analyze the value of mNGS in clinical application. Three hundred sixty-nine patients with a specific CNS infection diagnosis were enrolled, and their clinical data were collected. CDI and DDI were defined in our study to describe the intensity of drug use in different groups. We also used LOH and mRS to evaluate whether the application of mNGS could benefit CNS infection patients. Results mNGS reported a 91.67% sensitivity in culture-positive patients and an 88.24% specificity compared with the final diagnoses. Patients performed with the mNGS test had less drug use, both total (58.77 vs. 81.18) and daily (22.6 vs. 28.12, p <0.1, McNemar) intensity of drug use, as well as the length of hospitalization (23.14 vs. 24.29). Patients with consciousness grading 1 and 3 had a decrease in CDI (Grade1, 86.49 vs. 173.37; Grade 3, 48.18 vs. 68.21), DDI (Grade1, 1.52 vs. 2.72; Grade 3, 2.3 vs. 2.45) and LOH (Grade1, 32 vs. 40; Grade 3, 21 vs. 23) with the application of mNGS. Patients infected with bacteria in CNS had a reduced CDI, DDI, and LOH in the mNGS Group, in contrast with the TraE Group. 49% of patients altered medication plans, and 24.7% of patients reduced drug intensity four days after mNGS reports, mostly due to the reduction of drug types. Conclusion mNGS showed its high sensitivity and specificity characteristics. mNGS may assist clinicians with more rational medication regimens and reduce the drug intensity of patients, of which the primary way was to reduce the variety of drugs, especially for severe patients and bacterial infections. mNGS has the potential value of improving the prognosis of CNS infectious patients.

Nghiên cứu đặc điểm lâm sàng và cận lâm sàng nhiễm trùng thần kinh trung ương ở trẻ em

2021 ◽  
Author(s):  
Vinh Phu Tran
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Infection ◽  
Clinical Manifestations ◽  
Inverse Correlation ◽  
Altered Mental Status ◽  
Cns Infection ◽  
Common Disease ◽  
Psychological Consequences ◽  
Cns Infections

Đặt vấn đề: Nhiễm trùng thần kinh trung ương (NTTKTW) là bệnh lý thường gặp, để lại nhiều hậu quả về sức khỏe cũng như tâm lý nặng nề cho từng gia đình cũng như toàn xã hội. Bệnh có tỉ lệ tử vong cao, đặc biệt là trẻ em. Biểu hiện lâm sàng nhiễm trùng thần kinh trung ương ở trẻ em rất đa dạng và thay đổi theo lứa tuổi. Việc phát hiện triệu chứng nghi ngờ để chẩn đoán sớm có ý nghĩa quan trọng, góp phần cải thiện tiên lượng bệnh qua việc quyết định điều trị sớm. Đối tượng: 61 trường hợp bệnh nhi được chẩn đoán và điều trị NTTKTW tại Trung tâm Nhi khoa Bệnh viện Trung ương Huế. Phương pháp nghiên cứu: Mô tả cắt ngang. Kết quả: NTTKTW hay gặp nhất ở nhóm trẻ > 5 tuổi (chiếm 52,5%); Các triệu chứng cơ năng thường gặp là ăn, bú kém (62,8% VMN, 98,9% viêm não), đau đầu (34,9% VMN, 61,1% viêm não), nôn (48,8% VMN, 38,9% viêm não); Các dấu hiêu thực thể thường gặp là sốt (79,1% VMN, 73,3% viêm não), rối loạn tri giác (79% VMN, 22,7% viêm não), hội chứng tăng áp lực nội sọ (65,1% VMN, 72,2% viêm não), hội chứng kích thích màng não (36,6% VMN, 22,2% viêm não), co giật (14% VMN, 44,4% viêm não, p < 0,05). Có mối tương quan nghịch giữa sự biến đổi tri giác ban đầu của bệnh nhi (đánh giá bằng thang điểm glasgow) với tần số tim (r = -0,412), tần số thở (r = -0,33), thời gian nằm viện (r = -0,612) và số lượng tế bào trong dịch não tủy (VMNM r = -0,575); VMN tăng lympho r = -0,686, VN r = -0,804). Kết luận: Biểu hiện lâm sàng của các nhóm bệnh lý nhiễm trùng thần kinh khá đa dạng, biến đổi tri giác ban đầu bệnh nhi là yếu tố tiên lượng bệnh. Từ khóa: Lâm sàng, cận lâm sàng, nhiễm trùng thần kinh trung ương trẻ em. ABSTRACT CLINICAL AND SUBCLINICAL CHARACTERISTICS OF CENTRAL NERVOUS SYSTEM INFECTION IN CHILDREN Background: Central nervous system infection (CNS) is a common disease, leading to many serious health and psychological consequences for each family’s patient as well as the whole society. The disease has a high mortality rate, especially in children. Clinical manifestations of CNS infections in children are variable, depending on age.Detecting suspicious symptoms for early diagnosis is important, contributing to improving prognosis through early treatment decisions. Subjects: 61 cases of patients diagnosed and treated at Pediatrics Center in Hue Central Hospital. Methods: Prospective observational study. Results:It showed that CNS infections are most common in children > 5 years old (52.5%); Commonsymptoms were poor feeding (62.8% meningitis, 98.9% encephalitis), headache (34.9% meningitis, 61.1% encephalitis), vomiting (48.8% meningitis, 38.9% encephalitis); Commonsigns are fever (79.1% meningitis, 73.3% encephalitis), altered mental status (79% meningitis, 22.7% encephalitis), increased intracranial pressure syndrome (65.1% meningitis,72.2% encephalitis), convulsions (14% meningitis, 44.4% encephalitis, p < 0.05). There is an inverse correlation between the change in the patient’s initial consciousness (assessed by the glasgow scale) with heart rate (r = -0.412), respiratory rate (r = -0.33), duration of hospitalization(r = -0.612) and the number of cells in the cerebrospinal fluid. Conclusions: Clinical manifestations of CNS infection are variable, the initial change in the patient’s consciousness is a predictor of the disease. Key words: Clinical, subclinical, Central Nervous System Infections.

scholarly journals Cranial Imaging and Lumbar Puncture in Patients With Suspected Central Nervous System Infection

2019 ◽  
Vol 70 (12) ◽  
pp. 2469-2475 ◽  
Author(s):  
Joost M Costerus ◽  
Cynthia M C Lemmens ◽  
Diederik van de Beek ◽  
Matthijs C Brouwer
Keyword(s):  
Emergency Department ◽  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Antibiotic Administration ◽  
Treatment Delays ◽  
Cns Infections ◽  
Poor Outcomes ◽  
The Times

Abstract Background Performing cranial imaging prior to lumbar punctures (LPs) in patients with suspected central nervous system (CNS) infections has been associated with delayed treatments and poor outcomes. Various guidelines provide different criteria for cranial imaging prior to LP. Methods We describe the use of cranial imaging in a cohort of adult patients with suspected CNS infections, and evaluated adherence to the recommendations made in the Infectious Disease Society of America (IDSA), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Swedish, and Dutch guidelines. We also analyzed the association between cranial imaging and the time between emergency department entrance and intravenous antibiotic administration. Results From 2012–2015, 203 patients with suspected CNS infections were included, of whom 56 (27%) were diagnosed with CNS infections and 16 were diagnosed with bacterial meningitis (8%). Cranial imaging, in all cases computed tomography (CT), was performed in 130 patients (64%) and led to the deferral of LPs in 7 (5%). Criteria by the IDSA, ESCMID, Swedish, and Dutch guidelines showed indications for imaging in 64%, 39%, 39%, and 40% of patients, respectively. The times between emergency department arrivals and the start of antibiotic therapy between patients with and without CT before LP were similar (median 134 [interquartile range (IQR) 58–292] vs. 141 minutes [IQR 52–227], respectively; Mann-Whitney U P = .74). Conclusions A cranial CT prior to LP was done in the majority of patients with a suspected CNS infection, irrespective of guideline indications. The ESCMID, Swedish, and Dutch guidelines were more restrictive in advising imaging, compared to the IDSA guidelines. Performing cranial imaging prior to LP was not associated with treatment delays in this Dutch cohort study.

scholarly journals 045 Primary cutibacterium acnes central nervous system infection causing focal seizures: an unusual presentation of a rare disease

2019 ◽  
Vol 90 (e7) ◽  
pp. A15.2-A15
Author(s):  
Sophie E Waller ◽  
Sarah Browning ◽  
Elizabeth Pepper
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Delayed Presentation ◽  
Pathogenic Potential ◽  
Focal Seizures ◽  
Device Infection ◽  
Cutibacterium Acnes ◽  
Neurosurgical Intervention

IntroductionCutibacterium acnes is a Gram positive, anaerobic bacterium of low pathogenic potential that forms part of the normal cutaneous flora. Although most often identified as a contaminant in culture of microbiological specimens, it is commonly implicated in both postoperative wound and implantable device infection. Neurosurgical device infections secondary to C. acnes are well recognised and are likely secondary to bacterial contamination from the skin during surgery. Indolent infection characterised by delayed presentation of weeks to months following intervention is common. C. acnes infection involving the central nervous system (CNS) in the absence of previous neurosurgical intervention is rare, but has been described following dental or mastoid infections and following facial trauma. A further case series has reported de novo C. acnes CNS infection occurring in the absence of these recognised risk factors, but with clinical features of meningitis being common to all.Methods and resultsWe describe a unique case of primary C. acnes extra-dural collection in a previously well patient with no neurosurgical history presenting with sub-acute focal seizures and progressive focal leptomeningeal thickening on MRI.ConclusionC. acnes CNS infection can occur in the immunocompetent and in the absence of neurosurgical intervention.

scholarly journals Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

2021 ◽  
Author(s):  
Nanda Ramchandar ◽  
Nicole G Coufal ◽  
Anna S Warden ◽  
Benjamin Briggs ◽  
Toni Schwarz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Usual Care ◽  
Transcriptomic Analysis ◽  
Cns Infection ◽  
Metagenomic Sequencing ◽  
Next Generation ◽  
Cns Infections ◽  
Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

scholarly journals 1417. Detection of Human Herpesviruses DNA in Cerebrospinal Fluids of Patients Suspected with Central Nervous System Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S516-S516
Author(s):  
Yuki Higashimoto ◽  
Soichiro Ishimaru ◽  
Hiroki Miura ◽  
Kei Kozawa ◽  
Masaru Ihira ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Mri ◽  
Central Nervous System Infection ◽  
Clinical Manifestations ◽  
Rflp Analysis ◽  
Cns Infection ◽  
Characteristic Change ◽  
Human Herpesviruses ◽  
Hsv 1

Abstract Background Of the nine human herpesviruses (HHVs), most viruses have neurovirulence. Clinical manifestations of central nervous system (CNS) complications caused by some of the HHVs are well examined in children and immunocompromised adults; however, information of EBV and β-herpesviruses in an immunocompetent adult is limited. Methods Between April 2013 and March 2018, 322 patients (median age; 51.6 years old, male/female; 196/126) suspected to CNS infection were enrolled in this study. Patients with unconsciousness or characteristic change lasting more than 24 hours and abnormal brain MRI or EEG were defined as encephalitis. Real-time PCRs for detection of the 7 HHVs DNA including HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-7 were carried out in DNA extracted from 200 μL CSF. HHV-6 was discriminated between HHV-6A and HHV-6B using RFLP analysis. Results Herpesviruses DNA was detected in 33 (10.2%) of the 322 patients. The most frequently detected HHVs was VZV (19 cases) and followed by HHV-6B (4 cases), HSV-1 (3 cases), HSV-2 (3 cases), and EBV (2 cases). Multiple HHVs DNAs were detected from the 2 patients (case A; HSV-2, HHV-6, and EBV, case B; EBV and HHV-6B). No CMV and HHV-7 DNAs were detected in any of the samples. Eleven cases were assigned as encephalitis, and other 22 cases were non-encephalitis. Although all 3 patients with positive HSV-1 DNA were encephalitis, all 3 patients with positive HSV-2 DNA were meningitis. Fourteen (13 patients had zoster) of the 19 patients with positive VZV DNA were meningitis, and the remaining 5 patients (4 patients had zoster) were encephalitis. Two of the 4 HHV-6B-positive patients were non-encephalitis, one patient was diagnosed Orbital apex syndrome and another patient was myelitis. One of the 2 encephalitis patient was chromosomally integrated (ci) HHV-6. Additionally, case B was also ciHHV-6. Conclusion Approximately 10% of the samples were positive of HHVs DNA. VZV was the most frequently detected viral DNA in this cohort. Thirty-three percent of the patients were encephalitis, remaining patients were non-encephalitis such as meningitis and myelitis. As suggested, ciHHV-6 can cause miss-diagnosis of patients suspected with CNS infection. Disclosures All authors: No reported disclosures.

scholarly journals Combination Antifungal Therapy in the Treatment ofScedosporium apiospermumCentral Nervous System Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Andrés F. Henao-Martínez ◽  
José R. Castillo-Mancilla ◽  
Michelle A. Barron ◽  
Aran Cunningham Nichol
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Antifungal Therapy ◽  
Successful Treatment ◽  
Surgical Debridement ◽  
Prolonged Treatment ◽  
Cns Infection ◽  
Scedosporium Apiospermum ◽  
Cns Infections

Treatment ofScedosporium apiospermumcentral nervous system (CNS) infection typically consists of an azole in combination with surgical debridement. This approach requires prolonged treatment and carries a high associated mortality. We present two cases of the successful treatment ofS. apiospermumCNS infections with the combination of voriconazole and terbinafine.

scholarly journals Osteopontin ImpactsWest Nile virusPathogenesis and Resistance by Regulating Inflammasome Components and Cell Death in the Central Nervous System at Early Time Points

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Nikki Bortell ◽  
Claudia Flynn ◽  
Bruno Conti ◽  
Howard S. Fox ◽  
Maria Cecilia G. Marcondes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Infections ◽  
Early Time ◽  
Cns Infection ◽  
Critical Threshold ◽  
Type I ◽  
Time Points ◽  
Viral Spread ◽  
The Impact

Osteopontin (OPN) is a molecule that is common in central nervous system (CNS) pathologies, which participates in the activation, migration, and survival of inflammatory cells. However, the mechanisms by which OPN modulates inflammatory pathways are not clear. To understand the role of OPN in CNS viral infections, we used a lethal mouse model ofWest Nile virus(WNV), characterized by the injection of high doses of the Eg101 strain of WNV, causing the increase of OPN levels in the brain since early time points. To measure the impact of OPN in neuropathogenesis and resistance, we compared C57BI/6 WT with mice lacking the OPN gene (OPN KO). OPN KO presented a significantly higher mortality compared to WT mice, detectable since day 5 pi. Our data suggests that OPN expression at early time points may provide protection against viral spread in the CNS by negatively controlling the type I IFN-sensitive, caspase 1-dependent inflammasome, while promoting an alternative caspase 8-associated pathway, to control the apoptosis of infected cells during WNV infection in the CNS. Overall, we conclude that the expression of OPN maintains a critical threshold in the innate immune response that controls apoptosis and lethal viral spread in early CNS infection.

Moxalactam Therapy of Serious; Pediatric Infections

1984 ◽  
Vol 18 (9) ◽  
pp. 723-726 ◽  
Author(s):  
Michael D. Reed ◽  
Stephen C. Aronoff ◽  
Jeffrey L. Blumer
Keyword(s):  
Central Nervous System ◽  
Staphylococcus Aureus ◽  
Nervous System ◽  
Drug Therapy ◽  
Bacterial Infections ◽  
Multiple Sources ◽  
Cns Infections ◽  
The Central Nervous System ◽  
Pediatric Infections ◽  
In Infants And Children

Forty children with documented or suspected bacterial infections arising outside the central nervous system (CNS) were studied. Fifteen different pathogens for a total of 30 isolates were obtained from multiple sources. Staphylococcus aureus (minimum inhibitory concentrations 4–8 μg/ml) was the most common pathogen isolated, involving seven patients. Each patient received moxalactam 50 mg/kg iv over 15 minutes q8h and responded favorably to therapy, exhibiting bacteriologic and/or clinical cures. Toxicity associated with moxalactam occurred in only two patients and necessitated discontinuation of drug therapy. Moxalactam 50 mg/kg iv q8h is effective therapy for non-CNS infections occurring in infants and children.

scholarly journals Viral Infections of the Central Nervous System in Qatar: Epidemiology, Pathogenesis and Clinical Outcomes

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S305-S305
Author(s):  
Fatma Ben Abid ◽  
Mohammed Abukhattab ◽  
Obada Salameh ◽  
Ahmed Gohar ◽  
Muna Al Masalmani ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Outcomes ◽  
Southeast Asian ◽  
Case Definition ◽  
Etiologic Agent ◽  
Cns Infection ◽  
Viral Etiology ◽  
Varicella Zoster ◽  
Cns Infections

Abstract Background Viral central nervous system (CNS) infections are common causes of morbidity and mortality globally. There are no existing data about viral CNS infections in Gulf Cooperation Council countries. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcomes of viral central nerveous system infection in patients in Qatar. Methods We retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at any of the 7 hospitals in the Hamad Medical Corporation. We included those with an abnormal CSF findings and excluded those with missing medical records, no clinical evidence of CNS infection and those with proven bacterial infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, patients were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology. Results Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. The most common presenting signs and symptoms are listed in the table. Persons of Southeast Asian origin accounted for 39.6% of all infections. A definitive virologic etiologic agent was found in 38%, with enterovirus being the most common (44.3%) followed by Epstein–Barr virus (31%) and varicella-zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic. Conclusion Viral etiology is common among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections. Disclosures A. Butt, Merck: Investigator, Grant recipient

scholarly journals Anidulafungin Treatment of Candidal Central Nervous System Infection in a Murine Model

2009 ◽  
Vol 53 (8) ◽  
pp. 3576-3578 ◽  
Author(s):  
Cheol-In Kang ◽  
Mark S. Rouse ◽  
Jayawant N. Mandrekar ◽  
James M. Steckelberg ◽  
Robin Patel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Candida Albicans ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Murine Model ◽  
Potential Role ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Fungal Burden

ABSTRACT We established a murine model of Candida albicans central nervous system (CNS) infection and evaluated the efficacy of anidulafungin. Ten milligrams/kg/day anidulafungin, amphotericin B, or voriconazole significantly reduced mortality and fungal burden in brain tissue, although amphotericin B and 10 mg/kg/day anidulafungin reduced fungal burden in brain tissue to a greater extent than did voriconazole. This suggests a potential role for anidulafungin in the treatment of candidal CNS infection.

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