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Bacterial meningitis is a devastating disease with significant morbidity and mortality, especially in neonates and young infants. The overall incidence of meningitis has decreased with focused screening, public health interventions, and vaccination, but the disease remains a significant concern in high-risk groups. In this review, we provide an update on bacterial meningitis in children younger than age 60 days, including epidemiology, clinical presentation, diagnostic approaches, treatment, and prognosis. [ Pediatr Ann . 2024;53(11):e425-e432.] .

Inflammatory causes of stroke are frequent and often pose diagnostic and therapeutic challenges due to the scarcity of randomized trials and the absence of clear guideline recommendations for many scenarios. Following the publication of the recommendations of the European Stroke Organization on primary angiitis of the central nervous system (PACNS) last year, the German Neurological Society (DGN) has issued very clear guidelines this year on the diagnostics and treatment of PACNS and updated the recommendations for systemic vasculitides; however, stroke often occurs not only as a result of primary vascular inflammation but also as a complication of another organ infection. Approximately 5% of all patients with sepsis, ca. 20% of patients with bacterial meningitis and up to 40% of patients with bacterial endocarditis suffer from a stroke as a complication. This article summarizes the key characteristics of these inflammatory causes of stroke and particularly focuses on the current recommendations for diagnostic and therapeutic management., (© 2024. The Author(s).)

Background: To inform World Health Organization guidelines for the management of serious bacterial infection (SBI) (suspected or confirmed sepsis, pneumonia, or meningitis) in infants aged 0-59 days., Objective: To conduct an "overview of systematic reviews" to: (1) understand which systematic reviews have examined diagnosis and management of SBI in infants aged 0-59 days in the last 5 years; and (2) assess if the reviews examined PICOs (population, intervention, comparator, outcomes) and regimens currently being recommended in low and middle income countries (LMICs) by the World Health Organization., Data Sources: MEDLINE; Embase; Cochrane Library; Epistemonikos; PROSPERO., Study Selection: Systematic reviews of randomized controlled trials or observational studies of infants aged 0-59 days examining diagnostic accuracy and antibiotic regimens for SBI from January 1, 2018 to November 3, 2023., Data Extraction: Dual independent extraction of study characteristics, PICOs, and methodological quality., Results: Nine systematic reviews met our criteria. Two reviews examined diagnostic accuracy for sepsis, and no reviews examined pneumonia or meningitis. Five reviews examined antibiotic effectiveness (sepsis [n = 4]; pneumonia [n = 1]), and no reviews examined meningitis. One review examined antibiotic duration for sepsis and one for meningitis, and no reviews for pneumonia. Only 4 of the 9 systematic reviews met criteria for high-quality., Limitations: Our review was limited to the last 5 years to inform current guideline updates., Conclusions: Few studies have examined antibiotic regimens currently being used in LMICs and quality is of concern in many studies. More high-quality data are needed to inform management of SBI in newborns, especially in LMICs.

Acute bacterial meningitis (ABM) is associated with severe morbidity and mortality. The most prevalent pathogens in community-acquired ABM are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Other pathogens may affect specific patient groups, such as newborns, older patients, or immunocompromised patients. It is well established that ABM is associated with elevated intracranial pressure (ICP). However, the role of ICP monitoring and management in the treatment of ABM has been poorly described.An electronic search was performed in four electronic databases: PubMed, Web of Science, Embase, and the Cochrane Library. The search strategy chosen for this review used the following terms: Intracranial Pressure AND (management OR monitoring) AND bacterial meningitis. The search yielded a total of 403 studies, of which 18 were selected for inclusion. Eighteen studies were finally included in this review. Only one study was a randomized controlled trial. All studies employed invasive ICP monitoring techniques, whereas some also relied on assessment of ICP-based on clinical and/or radiological observations. The most commonly used invasive tools were external ventricular drains, which were used both to monitor and treat elevated ICP. Results from the included studies revealed a clear association between elevated ICP and mortality, and possibly improved outcomes when invasive ICP monitoring and management were used. Finally, the review highlights the absence of clear standardized protocols for the monitoring and management of ICP in patients with ABM. This review provides an insight into the role of invasive ICP monitoring and ICP-based management in the treatment of ABM. Despite weak evidence certainty, the present literature points toward enhanced patient outcomes in ABM with the use of treatment strategies aiming to normalize ICP using continuous invasive monitoring and cerebrospinal fluid diversion techniques. Continued research is needed to define when and how to employ these strategies to best improve outcomes in ABM., (© 2024. The Author(s).)

Objective: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis., Methods: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group ( n  = 27) and infectious meningitis with mNGS (-) group ( n  = 26), respectively., Results: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group ( p  < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]., Conclusion: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Background: Given the lack of evidence-based guidelines for hypothermic infants, providers may be inclined to use febrile infant decision-making tools to guide management decisions. Our objective was to assess the diagnostic performance of febrile infant decision tools for identifying hypothermic infants at low risk of bacterial infection., Methods: We conducted a secondary analysis of a retrospective cohort study of hypothermic (≤36.0 C) infants ≤90 days of age presenting to the emergency department or inpatient unit among 9 participating sites between September 1, 2016 and May 5, 2021. Well-appearing infants evaluated for bacterial infections via laboratory testing were included. Infants with complex chronic conditions or premature birth were excluded. Performance characteristics for detecting serious bacterial infection (SBI; urinary tract infection, bacteremia, bacterial meningitis) and invasive bacterial infection (IBI; bacteremia, bacterial meningitis) were calculated for each tool., Results: Overall, 314 infants met the general inclusion criteria, including 14 cases of SBI (4.5%) and 7 cases of IBI (2.2%). The median age was 5 days, and 68.1% of the infants (214/314) underwent a full sepsis evaluation. The Philadelphia, Boston, IBI Score, and American Academy of Pediatrics Clinical Practice Guideline did not misclassify any SBI or IBI as low risk; however, they had low specificity and positive predictive value. Rochester and Pediatric Emergency Care Applied Research Network tools misclassified infants with bacterial infections., Conclusions: Several febrile infant decision tools were highly sensitive, minimizing missed SBIs and IBIs in hypothermic infants. However, the low specificity of these decision tools may lead to unnecessary testing, antimicrobial exposure, and hospitalization., (Copyright © 2024 by the American Academy of Pediatrics.)

Febrile seizures, which are relatively common in young children, are often triggered by an infection and resolve quickly. Prompt presentation to a pediatric department is mandatory after any first seizure and every time for children ≤ 12 months. Central nervous system (CNS) diseases in childhood are able to cause seizures or other neurological disorders. Even the slightest suspicion of a seizure with CNS involvement must be promptly treated. In case of doubt, both an antiviral and an antibacterial treatment are started in parallel, which can be stopped after detecting the pathogen. Lumbar puncture is strictly indicated unless there are contraindications. Meningococcal sepsis is a severe clinical feature comprising high fever, chills and disorders of consciousness. The first skin symptoms are petechiae as a red flag sign. With progression, potentially lethal purpura fulminans may develop. Waterhouse-Friderichsen syndrome is a severe complication of acute bacterial meningitis. Lethality rate is 35%. The pediatric assessment triangle and the ABCDE algorithm help to identify critically ill children in a standardized, structured, and rapid manner., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Simulation in the preclinical medical education setting is a beneficial tool for students to develop clinical skills, supplement preexisting knowledge, and prepare for clinical rotations and beyond. We detail the complete simulation scenario, including a participant postresponse questionnaire, of a 28-year-old male who developed bacterial meningitis after experiencing an upper respiratory infection in the days prior., Methods: Simulation fellows and faculty at the Alabama College of Osteopathic Medicine created a simulation scenario pertaining to bacterial meningitis. The scenario utilized a high-fidelity patient simulator, one standardized participant for patient voiceover, one standardized participant as a patient family member, and one standardized participant as a physician consultant on an as-needed basis. Sixteen preclinical medical students from various specialty interest groups were recruited to participate in the scenario and complete the postscenario questionnaire., Results: The simulation scenario was well received by the participants, and 15 of 16 completed the postscenario questionnaire. Ninety-three percent strongly agreed the simulation was a valuable clinical experience. Additionally, 73% of participants strongly agreed that the simulation experience was realistic, 80% strongly agreed that it tested their clinical reasoning ability, and 53% strongly agreed it was appropriate for their level of clinical knowledge., Discussion: Medical simulation is a valuable educational tool tailored to maximize student learning and supplement the traditional didactic curriculum. The successful development and implementation of our meningitis simulation case further supports the continued use of medical simulation in the preclinical setting., (© 2023 Cohen et al.)

Bacterial meningitis after percutaneous radiofrequency trigeminal ganglion is a rare but severe complication. In this article, we report a case of meningitis due to Streptococcus parasanguinis and review the related literature. A 62-year-old male patient with uremia and severe trigeminal neuralgia presented to another hospital and was offered to undergo radiofrequency treatment for a trigeminal ganglion lesion (2022.08.05). The next day (2022.08.06), he presented with a headache and right shoulder and back pain. The pain continued to worsen, so he came to our hospital (The First Affiliated Hospital of Wannan Medical College) and received a diagnosis of bacterial meningitis, which was confirmed by a lumbar puncture. The patient was treated with appropriate antibiotics, and subsequently recovered before being discharged. Although this complication is relatively rare, its progression is rapid. Meningitis must be suspected when a patient presents with headache, fever, and other symptoms associated with meningitis within days after undergoing radiofrequency treatment for a trigeminal ganglion lesion, especially if the patient has an underlying disease that causes a decline in immunity. We discuss this case in terms of clinical presentation, time of onset, treatment, prognosis, past history, and sex. Although early detection of this complication is beneficial, it is better to effectively prevent its occurrence.

Meningitis remains an important cause of mortality and morbidity. Clinicians should be alert to this diagnosis and have a low threshold for investigation and treatment of meningitis. This article provides an update of current evidence and existing guidelines for the management of suspected acute meningitis in adults in the UK., (© Royal College of Physicians 2022. All rights reserved.)

Objectives: Recurrent bacterial meningitis (RBM) is a rare but life-threatening disease. This study aims to analyze the clinical features, potential causes, and therapeutic outcomes of RBM in children., Methods: This article retrospectively reviews the clinical characteristics, etiologies, and treatments in children with RBM hospitalized in Hebei children's hospital from 2012 to 2020., Results: A total of 10 children with RBM, five males and five females, were included in this study. The age of RBM in children spans from the neonatal stage to the childhood stage. The underlying illnesses were identified and classified as cerebrospinal fluid rhinorrhea (1 case), humoral immunodeficiency with Mondini dysplasia (1 case), common cavity deformity with cerebrospinal fluid ear leakage (1 case), Mondini malformations (2 cases), incomplete cochlear separation type I with a vestibular enlargement (2 cases), local inflammation of the sphenoid bone caused by cellulitis (1 case), congenital skull base defects (1 case), and congenital dermal sinus with intraspinal abscess (1 case). 6 patients chose targeted therapy for potential reasons., Conclusions: Congenital abnormalities or acquired injuries lead to intracranial communication with the outside world, which can quickly become a portal for bacterial invasion of the central nervous system, resulting in repeated infections., Competing Interests: All the authors declare that they have no conflict of interest., (Copyright © 2022 Xin Li et al.)

Background: To examine the clinical characteristics and therapeutic outcome of Escherichia (E.) coli adult bacterial meningitis (ABM)., Methods: The demographic data, clinical and laboratory features and therapeutic outcome of 25 E. coli ABM patients were examined retrospectively. The clinical features of the reported E. coli ABM cases were also included for analysis., Results: The 25 E. coli ABM patients included 12 women and 13 men, aged 33-78 years (mean= 59.9). Of these 25 patients, 13 had a postneurosurgical state as the underlying condition. As to the underlying medical conditions, diabetes mellitus was the most common, found in 9 of the 25 cases. Of the clinical manifestation, severe neurologic manifestations including altered consciousness (19), hydrocephalus (10), seizure (7) acute/subacute cerebral infarct (5), brain abscess (2), subdural empyema (1) and spinal abscess (1) were found, and the other clinical features included fever (21), septic shock (8), bacteremia (6) and hyponatremia (3). With treatment, the mortality rate was more than 44.0% and the presence of septic shock was a significant prognostic factor. With literature review, 29 community-acquired and 12 postneurosurgical E. coli ABM cases were enrolled, and severe neurologic manifestation and high mortality rate were also found., Conclusions: This preliminary overview of E. coli ABM revealed the underlying conditions, severe neurologic manifestation and high mortality rate. Further large-scale, prospective study is needed for a better delineation of this specific infectious syndrome of adult E. coli meningitis.

Our objective was to quantify the differences in the outcomes from childhood bacterial meningitis (BM) and to describe the factors associated with them in different parts of the world. This study is a secondary analysis of prospectively collected data from five clinical BM trials conducted in Finland, Latin America (LatAm), and Angola between 1984 and 2017. As all data were collected uniformly, direct comparison of the series was possible. Associations between patient characteristics and death or dismal outcome-the triad of death, severe neurological sequelae, or deafness-were explored. In all, data on 2123 children with BM were analyzed. Etiology was confirmed in 95%, 83%, and 64%, in Finland, LatAm and Angola, respectively. The leading agents were Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Dismal outcome was the end result for 54%, 31%, and 5% of children in Angola, LatAm, and Finland, respectively. Although underweight, anemia, and tardy arrival worsened prognoses in Angola and LatAm, it was the presenting condition that was central in terms of outcome. In multivariate analysis, the factors independently associated with dismal outcome were the study site (Angola vs. Finland, OR 11.91, 95% CI 5.54-25.63, p < 0.0001 or LatAm vs. Finland, OR 9.46, 95% CI 4.35-20.61, p < 0.0001), Glasgow Coma Score < 13 (OR 4.58, 95% CI 3.31-6.32, p < 0.0001), seizures (OR 1.96, 95% CI 1.43-2.69), age < 1 year (OR 1.55, 95% CI 1.13-2.14, p = 0.007), and pneumococcal etiology (OR 1.49, 95% CI 1.08-2.06, p = 0.015). Greatly dissimilar outcomes from BM reflected the findings on admission on all three continents. Optimizing growth, preventing anemia, and prompt treatment may improve outcomes in resource poor areas., (© 2021. The Author(s).)

Objective: Community-acquired bacterial meningitis (CABM) is a severe condition associated with high mortality. In this study the first aim was to evaluate the incidence of intracranial pressure (ICP) insults and disturbances in cerebral vasomotor reactivity and the second aim was to evaluate the management and clinical outcome of CABM patients treated in the neurointensive care unit (NICU)., Methods: CABM patients who were treated in the NICU of Uppsala University Hospital, Sweden, during 2008-2020 were included in the study. Data on demographics, admission variables, treatment, ICP dynamics, vasomotor reactivity, and short-term clinical outcome were evaluated in these patients., Results: Of 97 CABM patients, 81 (84%) received ICP monitoring, of whom 22% had ICP > 20 mm Hg during 5% or more of the monitoring time on day 1, which decreased to 9% on day 3. For those patients with ICP monitoring, 46% required CSF drainage, but last-tier ICP treatment, including thiopental (4%) and decompressive craniectomy (1%), was rare. Cerebral vasomotor reactivity was disturbed, with a mean pressure reactivity index (PRx) above 0.2 in 45% of the patients on day 1, and remained high for the first 3 days. In total, 81 (84%) patients had a favorable outcome (Glasgow Coma Scale motor score [GCS M] 6) at discharge, 9 (9%) patients had an unfavorable outcome (GCS M < 6) at discharge, and 7 (7%) patients died in the NICU. Those with favorable outcome had significantly better cerebral vasomotor reactivity (lower PRx) than the two other outcome groups (p < 0.01)., Conclusions: Intracranial hypertension was frequent following severe CABM and CSF drainage was often sufficient to control ICP. Cerebral vasomotor reactivity was commonly disturbed and associated with poor outcome. Clinical outcome was slightly better than in earlier studies.

Background: Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection., Case Presentation: We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135-1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36-2.259 g/l) and decreased CSF glucose (0.45-1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient's condition improved after treatment with erythromycin for approximately 5 weeks., Conclusions: Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

Bacterial meningitis is a neurological emergency with high morbidity and mortality. We herein investigated clinical features, etiology, antimicrobial susceptibility profiles, and prognosis of bacterial meningitis in adults from a single tertiary center. We retrospectively reviewed medical records of patients with laboratory-confirmed bacterial meningitis from 2007 to 2016. Patients with recent neurosurgery, head trauma, or indwelling neurosurgical devices were classified as having healthcare-related meningitis. Causative microorganisms were identified by analyzing cerebrospinal fluid (CSF) and blood cultures, and antimicrobial susceptibility profiles were evaluated. We performed multiple logistic regression analysis to identify factors associated with unfavorable outcomes. We identified 161 cases (age, 55.9 ± 15.5 years; male, 50.9%), of which 43 had community-acquired and 118 had healthcare-related meningitis. CSF and blood culture positivity rates were 91.3% and 30.4%, respectively. In community-acquired meningitis patients, Klebsiella pneumoniae (25.6%) was the most common isolate, followed by Streptococcus pneumoniae (18.6%) and Listeria monocytogenes (11.6%). The susceptibility rates of K. pneumoniae to ceftriaxone, cefepime, and meropenem were 85.7%, 81.3%, and 100%, respectively. Among healthcare-related meningitis patients, the most common bacterial isolates were coagulase-negative staphylococci (28.0%), followed by Staphylococcus aureus (16.1%) and Enterobacter spp. (13.6%). Neurological complications occurred in 39.1% of the patients and the 3-month mortality rate was 14.8%. After adjusting for covariates, unfavorable outcome was significantly associated with old age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.06), neurological complications (OR 4.53, 95% CI 1.57-13.05), and initial Glasgow coma scale ≤ 8 (OR 19.71, 95% CI 4.35-89.40). Understanding bacterial pathogens and their antibiotic susceptibility may help optimize antimicrobial therapy in adult bacterial meningitis.

To compare clinical features and outcomes between early and late onset of neonatal bacterial meningitis (NBM).Patients were allocated in 2 groups: early onset neonatal bacterial meningitis (ENBM) and late onset neonatal bacterial meningitis (LNBM). Data analysis includes asphyxia at birth, premature rupture of membranes (PROM), amnionitis, amniotic fluid contamination, maternal age, clinical manifestations of the patients, laboratory findings, radiological results, complications related to meningitis, duration of hospitalization and therapeutic effect.There was no difference in gender, birth weight, gestational age, and incidence of asphyxia between 2 groups. The incidence of PROM, chorioamnionitis and amniotic fluid contamination, proportion of small-for-gestational-age infants, convulsions, intracranial hemorrhage, hyperbilirubinemia, and the protein level of cerebrospinal fluid in ENBM group were higher than that in LNBM group (P < .05); the proportion of fever, elevated C-reaction protein and the abnormal of platelet counts in LNBM group was higher than that in ENBM group (P < .05). There was no difference in the incidence of complications and hospitalization time between 2 groups. The rate of effective treatment in LNBM group was significantly higher than that in ENBM group (P < .05).Patients with conditions of amniotic fluid contamination, chorioamnionitis, small-for-gestational-age and PROM might be more prone to develop ENBM and ENBM had worse outcomes than LNBM.

Acute bacterial meningitis (ABM) is a rare but disabling infectious condition that requires a performant multidisciplinary management approach. Between 70 and 90 adult patients are diagnosed with community-acquired ABM in Belgium annually, and reported case fatality rates range from 17 to 40%. The currently available guidelines provide evidence-based guidance on how to manage this disease. However, these guidelines do not translate the evidence to the daily practice at the emergency department in a Belgian healthcare context. We created a taskforce in University Hospitals Leuven consisting of experts with complementary expertise in managing this disease: neurology, neurosurgery, intensive care medicine, microbiology and infectious diseases. The taskforce agreed upon a flowchart containing seven management steps encompassing all relevant phases in emergency ABM management. In addition to the focus on timely and adequate initiation of antimicrobial treatment, the flowchart and protocol also provide guidance on practical hurdles such as how to assess the safety of performing a lumbar puncture and when to refer patients to the intensive care department. This protocol was implemented in University Hospitals Leuven and fosters inter-disciplinary coordination of ABM care.

Spinal adhesive arachnoiditis (SAA) with cyst formation secondary to infectious meningitis is a rare clinical entity. These cysts can compress the spinal cord and cause neurologic decline. We present a case of a patient who underwent resection for an intradural schwannoma which was complicated post-operatively by bacterial meningitis and development of several recurrent thoracic arachnoid cysts. After two separate thoracic decompressions with lysis of intradural adhesions, a permanent ventriculoperitoneal shunt (VPS) was eventually placed with complete recovery of his symptoms. Our review of the literature showed that CSF shunts have previously been successfully used to treat spinal fluid collections. Although there are many factors to consider when treating these patients, CSF diversion may be beneficial for similar SAA presentations in order to simultaneously treat and prevent recurrence of symptoms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting further underlines the need for developing other technologies, such as phage therapy. We exploited an in vitro phage therapy model for studying bacterial neonatal meningitis based on Escherichia coli (E. coli) EV36, bacteriophage (phage) K1F and human cerebral microvascular endothelial cells (hCMECs). We show that phage K1F is phagocytosed and degraded by constitutive- and PAMP-dependent LC3-assisted phagocytosis and does not induce expression of inflammatory cytokines TNFα, IL-6, IL-8 or IFNβ. Additionally, we observed that phage K1F temporarily decreases the barrier resistance of hCMEC cultures, a property that influences the barrier permeability, which could facilitate the transition of immune cells across the endothelial vessel in vivo. Collectively, we demonstrate that phage K1F can infect intracellular E. coli EV36 within hCMECs without themselves eliciting an inflammatory or defensive response. This study illustrates the potential of phage therapy targeting infections such as bacterial neonatal meningitis and is an important step for the continued development of phage therapy targeting antibiotic-resistant bacterial infections generally.

Background: Knowing the individual child's risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors., Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure., Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores' results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson-Todd Scale (AUC = 0.79) was all associated with death., Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

Trapped fourth ventricle (TFV) as a complication of post-hemorrhagic hydrocephalus (PHH) is widely reported in the pediatric population with a prior history of ventriculo-peritoneal (VP) shunt placement. Characterized by disproportionate dilatation of the fourth ventricle on serial neuro-imaging, it is rarely encountered in the early course of preterm infants and the differentiating clinical features are subtle and non-specific. Clinical alertness and sonographic correlation hold the key to early diagnosis. We report an early emergence of TFV in an extremely low gestational age newborn (ELGAN) following fulminant Pseudomonas aeruginosa meningitis, approach to management, and the neurological outcome. Fourth ventricle entrapment as a complication of perinatally acquired Pseudomonas aeruginosa meningitis in a surviving ELGAN is extremely rare.

Bacterial meningitis is most commonly caused by Streptococcus pneumoniae and Neisseria meningitidis and continues to pose a major public health threat. Morbidity and mortality of meningitis are driven by an uncontrolled host inflammatory response. This comprehensive update evaluates the role of the complement system in upregulating and maintaining the inflammatory response in bacterial meningitis. Genetic variation studies, complement level measurements in blood and CSF, and experimental work have together led to the identification of anaphylatoxin C5a as a promising treatment target in bacterial meningitis. In animals and patients with pneumococcal meningitis, the accumulation of neutrophils in the CSF was mainly driven by C5-derived chemotactic activity and correlated positively with disease severity and outcome. In murine pneumococcal meningitis, adjunctive treatment with C5 antibodies prevented brain damage and death. Several recently developed therapeutics target C5 conversion, C5a, or its receptor C5aR. Caution is warranted because treatment with C5 antibodies such as eculizumab also inhibits the formation of the membrane attack complex, which may result in decreased meningococcal killing and increased meningococcal disease susceptibility. The use of C5a or C5aR antagonists to specifically target the harmful anaphylatoxins-induced effects, therefore, are most promising and present opportunities for a phase 2 clinical trial., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Acute bacterial meningitis (ABM) in adults is associated with a mortality that may exceed 30%. Immunization programs have reduced the global burden; in the UK, declining incidence but persistently high mortality and morbidity mean that clinicians must remain vigilant., Sources of Data: A systematic electronic literature search of PubMed was performed to identify all ABM literature published within the past 5 years., Areas of Agreement and Controversy: Clinical features cannot reliably distinguish between ABM and other important infectious and non-infectious aetiologies. Prompt investigation and empirical treatment are imperative. Lumbar puncture (LP) and cerebrospinal fluid microscopy, biochemistry and culture remain the mainstay of diagnosis, but molecular techniques are increasingly useful. The 2016 UK joint specialist societies' guideline provides expert recommendations for the management of ABM, yet published data suggest clinical care delivered in the UK is frequently not adherent. Anxiety regarding risk of cerebral herniation following LP, unnecessary neuroimaging, underutilization of molecular diagnostics and suboptimal uptake of adjunctive corticosteroids compromise management., Growing Points: There is increasing recognition that current antibiotic regimens and adjunctive therapies alone are insufficient to reduce the mortality and morbidity associated with ABM., Areas Timely for Developing Research: Research should be focused on optimization of vaccines (e.g. pneumococcal conjugate vaccines with extended serotype coverage), targeting groups at risk for disease and reservoirs for transmission; improving adherence to management guidelines; development of new faster, more accurate diagnostic platforms (e.g. novel point-of-care molecular diagnostics); and development of new adjunctive therapies (aimed at the host-inflammatory response and bacterial virulence factors)., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Infants ≤28 days of age with fever are frequently hospitalized while undergoing infectious evaluation. We assessed differences in rates of serious bacterial infection (SBI; bacteremia, bacterial meningitis, urinary tract infection) and invasive bacterial infection (IBI; bacteremia, bacterial meningitis) among the following neonates: (1) febrile at presentation (FP), (2) afebrile with history of fever without subsequent fever during hospitalization, and (3) afebrile with history of fever with subsequent fever during hospitalization., Methods: We performed a single-center retrospective study of neonates evaluated for SBI during emergency department evaluation between January 1, 2006, and December 31, 2017. Patients were categorized into FP, afebrile with no subsequent fever (ANF), and afebrile with subsequent fever (ASF) groups. We compared rates of SBI and IBI between groups using logistic regression and assessed time to fever development using time-to-event analysis., Results: Of 931 neonates, 278 (29.9%) were in the ANF group, 93 (10.0%) were in the ASF group, and 560 (60.2%) were in the FP group. Odds of SBI in neonates ANF were 0.42 (95% confidence interval [CI] 0.23-0.79) compared with infants FP, although differences in IBI were not statistically significant (0.52, 95% CI 0.19-1.51). In infants ASF, median time to fever was 5.6 hours (interquartile range, 3.1-11.4). Infants ASF had higher odds of SBI compared to infants FP (odds ratio 1.93, 95% CI 1.07-3.50)., Conclusions: Neonates with history of fever who remain afebrile during hospitalization may have lower odds for SBI and be candidates for early discharge after an observation period., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Among young infants presenting with fever, untreated serious bacterial infections can have severe outcomes, so a full sepsis workup is often recommended but may not be necessary. This issue reviews the use of novel diagnostic tools such as procalcitonin, C-reactive protein, and RNA biosignatures as well as new risk stratification tools such as the Step-by-Step approach and the Pediatric Emergency Care Applied Research Network prediction rule to determine which febrile young infants require a full sepsis workup and to guide the management of these patients in the emergency department. The most recent literature assessing the risk of concomitant bacterial meningitis with urinary tract infections and the role for viral testing, specifically herpes simplex virus and enterovirus, are also reviewed.

Objectives: To evaluate the Full Outline of Unresponsiveness (FOUR) score as a predictor of outcome in adult patients with bacterial meningitis., Methods: We selected 427 patients from a nationwide, prospective cohort on community-acquired bacterial meningitis included from August 2011 to November 2016. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected. We compare the FOUR score with the Glasgow Coma Scale (GCS) score, performed a receiver operator characteristic curve analysis, and calculated the area under the curve (AUC) of the FOUR and GCS scores for the prediction of unfavorable outcome and mortality., Results: The median FOUR score on admission was 14 (interquartile range [IQR] 12-16), and the median GCS score was 12 (IQR 9-14). The outcome was unfavorable in 135 of 427 (32%) patients, of whom 55 (13%) died. There was a strong correlation between the FOUR score and the GCS score ( r = 0.85, p < 0.001). AUCs for the GCS and FOUR scores in the prediction of unfavorable outcome (both 0.64) and mortality (both 0.68) were comparable. Logistic regression analysis showed that the FOUR motor, brainstem, and respiration items were individual predictors of unfavorable outcome and mortality. For the GCS score, only the motor component was predictive, while the FOUR score provided a spectrum of clinical abnormalities in patients with a GCS score of 3., Conclusions: The FOUR score adds considerably to the prediction of outcome in patients with severe meningitis by means of better testing of the brainstem reflexes and respiration status. Future studies should consider incorporating the FOUR score into clinical assessment., (© 2019 American Academy of Neurology.)

Study Design: Retrospective case series., Objectives: To describe the epidemiological, clinical, MRI and therapeutic features and the outcomes of patients with syphilitic myelitis in a third-level hospital in Marrakesh in southern Morocco., Setting: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco., Methods: Twelve charts of persons with syphilitic myelitis over a period of 17 years were reviewed to determine demographics, presenting symptoms, clinical and radiological findings, biological features, treatment received and outcomes., Results: There were 120 reports of neurosyphilis. Twelve patients (10%) had syphilitic myelitis. Eleven patients (92%) were male with mean age of 44 at presentation. Tabes dorsalis was the most common clinical form. Cerebrospinal fluid analysis showed lymphocytic meningitis in nine patients (75%). Spine MRI was abnormal in four patients (33%). All patients were treated with 30 million units of aqueous penicillin G IV per day for 10 days, every 3 months. In follow-up, two patients (17%) with clinical syphilitic meningomyelitis improved significantly, eight patients (66%) with tabes dorsalis and subacute transverse myelitis showed partial improvement but clinical status was stationary for two patients (17%) with Erb paraplegia., Conclusions: All patients with myelopathy should undergo syphilitic serology because of nonspecific manifestations and curability of this disease., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

Background: Population exposure to Bacillus anthracis spores could cause mass casualties requiring complex medical care. Rapid identification of patients needing anthrax-specific therapies will improve patient outcomes and resource use., Objective: To develop a checklist that rapidly distinguishes most anthrax from nonanthrax illnesses on the basis of clinical presentation and identifies patients requiring diagnostic testing after a population exposure., Design: Comparison of published anthrax case reports from 1880 through 2013 that included patients seeking anthrax-related care at 2 epicenters of the 2001 U.S. anthrax attacks., Setting: Outpatient and inpatient., Patients: 408 case patients with inhalation, ingestion, and cutaneous anthrax and primary anthrax meningitis, and 657 control patients., Measurements: Diagnostic test characteristics, including positive and negative likelihood ratios (LRs) and patient triage assignation., Results: Checklist-directed triage without diagnostic testing correctly classified 95% (95% CI, 93% to 97%) of 353 adult anthrax case patients and 76% (CI, 73% to 79%) of 647 control patients (positive LR, 3.96 [CI, 3.45 to 4.55]; negative LR, 0.07 [CI, 0.04 to 0.11]; false-negative rate, 5%; false-positive rate, 24%). Diagnostic testing was needed for triage in up to 5% of case patients and 15% of control patients and improved overall test characteristics (positive LR, 8.90 [CI, 7.05 to 11.24]; negative LR, 0.06 [CI, 0.04 to 0.09]; false-negative rate, 5%; false-positive rate, 11%). Checklist sensitivity and specificity were minimally affected by inclusion of pediatric patients. Sensitivity increased to 97% (CI, 94% to 100%) and 98% (CI, 96% to 100%), respectively, when only inhalation anthrax cases or higher-quality case reports were investigated., Limitations: Data on case patients were limited to nonstandardized, published observational reports, many of which lacked complete data on symptoms and signs of interest. Reporting bias favoring more severe cases and lack of intercurrent outbreaks (such as influenza) in the control populations may have improved test characteristics., Conclusion: A brief checklist covering symptoms and signs can distinguish anthrax from other conditions with minimal need for diagnostic testing after known or suspected population exposure., Primary Funding Source: U.S. Department of Health and Human Services.

Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M . fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections.

A lumbar puncture (LP) is often essential for the diagnosis of bacterial meningitis. An LP can worsen brain displacement in case of a space-occupying lesion. Therefore, in selected patients a CT scan of the brain is made prior to performing the LP. However, the level of agreement between experts in diagnosing a contraindication for LP on CT scan is low. More importantly, in a substantial part of patients, empirical treatment with antibiotics was delayed due to the CT scan being performed first. The only effective treatment for patients with bacterial meningitis is early administration of antibiotics. Therefore, delay in administrating antibiotics should be prevented. Thus, should a CT scan of the brain be indicated, antibiotic treatment should be started before said imaging diagnostics and/or a potential LP procedure.

Bacterial infections of the central nervous system (CNS) continue to be an important cause of morbidity and mortality in children. The spectrum of bacterial infection of CNS includes; focal or multifocal infections like brain abscesses or subdural empyema; or more generalized or diffuse infections like pyogenic meningitis or ventriculitis. Focal and generalized infections may co-exist in an individual patient. Prompt and adequate antibiotic therapy and occasionally neurosurgical interventions are the cornerstone of effective management. The recent emergence of several multidrug-resistant bacteria poses a threat to the effective management of bacterial CNS infections. Several adjunctive anti-inflammatory and neuroprotective therapies are being tried, however; none has made a remarkable impact on the outcome. Consequently, bacterial CNS infections in children still remain a challenge to manage. In this review, authors discuss the current updates on the diagnostic and therapeutic aspects of bacterial infections of the CNS in children (post-neonatal age group).

The presentation of bacterial meningitis can overlap with viral meningitis and other conditions, and emergency clinicians must remain vigilant to avoid delaying treatment for a child with bacterial meningitis. Inflammatory markers, such as procalcitonin, in the serum and cerebrospinal fluid may help distinguish between bacterial meningitis and viral meningitis. Appropriate early antibiotic treatment and management for bacterial meningitis is critical for optimal outcomes. Although debated, corticosteroids should be considered in certain cases. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients.

Objective: To determine the outcome of children aged 2-14 years with cerebrospinal fluid (CSF) pleocytosis and at very low risk for bacterial meningitis managed as outpatients without antibiotics., Methods: Multicentre, prospective, observational study conducted at nine Spanish paediatric EDs. Patients were diagnosed with meningitis based on clinical suspicion of meningitis and CSF pleocytosis when evaluated in the ED. Children between 2 and 14 years of age with pleocytosis and very low-risk criteria for bacterial meningitis (well appearing, Bacterial Meningitis Score (BMS)=0, procalcitonin (PCT)<0.5 ng/mL and observation without deterioration for less than 24 hours in the ED) were treated as outpatients without antibiotics pending CSF cultures. The primary composite outcome was a final diagnosis of bacterial meningitis or return to the ED for clinical deterioration., Results: Of 182 children between 2 and 14 years old diagnosed with meningitis, 56 met the very low-risk criteria and 45 were managed as outpatients. None was diagnosed with bacterial meningitis or returned due to clinical deterioration. Another 31 patients with BMS=1 (due to a peripheral absolute neutrophil count (ANC)>10 000/mm 3 ) and PCT <0.5 ng/mL were managed as outpatients, diagnosed with aseptic meningitis and did well. BMS using PCT had the same sensitivity but greater specificity than classic BMS., Conclusions: This set of low-risk criteria appears safe for the outpatient management without antibiotics of children with CSF pleocytosis. Larger studies are needed to evaluate the predictive values of replacing peripheral ANC with PCT in the BMS., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013., Objectives: To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability., Search Methods: We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015)., Selection Criteria: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis., Data Collection and Analysis: Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence., Main Results: We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence)., Authors' Conclusions: Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Background: Early treatment is pivotal for favorable outcome in acute bacterial meningitis (ABM). Lumbar puncture (LP) is the diagnostic key. The aim was to evaluate the effect on outcome of adherence to European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), and Swedish guidelines regarding neuroimaging before LP., Methods: The cohort comprised 815 adult ABM patients in Sweden registered prospectively between 2008 and 2015. Primary endpoint was in-hospital mortality and secondary endpoint was favorable outcome at 2-6 months of follow-up., Results: Indications for neuroimaging before LP existed in 7%, 32%, and 65% according to Swedish, ESCMID, and IDSA guidelines, respectively. The adjusted odds ratio (aOR) was 0.48 (95% confidence interval [CI], .26-.89) for mortality and 1.52 (95% CI, 1.08-2.12) for favorable outcome if Swedish guidelines were followed. ESCMID guideline adherence resulted in aOR of 0.68 (95% CI, .38-1.23) for mortality and 1.05 (95% CI, .75-1.47) for favorable outcome. Following IDSA recommendations resulted in aOR of 1.09 (95% CI, .61-1.95) for mortality and 0.59 (95% CI, .42-.82) for favorable outcome. Performing prompt vs neuroimaging-preceded LP was associated with aOR of 0.38 (95% CI, .18-.77) for mortality and 2.11 (95% CI, 1.47-3.00) for favorable outcome. The beneficial effect of prompt LP was observed regardless of mental status and immunosuppression., Conclusions: Adherence to Swedish guidelines in ABM is associated with decreased mortality and increased favorable outcome in contrast to adherence to ESCMID or IDSA recommendations. Our findings support that impaired mental status and immunocompromised state should not be considered indications for neuroimaging before LP in patients with suspected ABM., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Fever increases mortality and morbidity and length of stay in neurocritically ill patients. Various methods are used in the neuroscience intensive care unit (NSICU) to control fever. Two such methods involve the Arctic Sun hydrogel wraps and the Gaymar cooling wraps. The purpose of our study was to compare these two methods in neurocritical care patients who had temperature >37.5°C for more than three consecutive hours and that was refractory to standard treatments. Data of patients requiring cooling wraps for treatment of hyperthermia at an NSICU at an academic, tertiary referral center were retrospectively reviewed. The average temperature before cooling was 38.5°C ± 0.38°C and 38.4°C ± 0.99°C for the Gaymar and Arctic Sun groups, respectively (p = 0.89). The Gaymar group took on average 16 ± 21.9 hours to reach goal temperature, whereas the Arctic Sun group took 2.22 ± 1.39 hours (p = 0.08). The average time outside of the target temperature was 57.0 ± 58.0 hours in the Gaymar group compared with 13.7 ± 17.1 hours in the Arctic Sun group (p = 0.04). Average duration of using the cooling wraps was similar between the two groups; 81.8% of patients had rebound hyperthermia in the Gaymar group compared with 20% in the Arctic Sun group (p = 0.0089). The Arctic Sun group had a nonsignificant increased incidence of shivering compared with the Gaymar group (40% vs. 18.18%, p = 0.36). We found that Arctic Sun surface cooling device was more efficient in attaining the target temperature, had less incidence of rebound hyperthermia, and was able to maintain normothermia better than Gaymar cooling wraps. The incidence of shivering tended to be more common in the Arctic Sun group.