The blood-brain barrier is a physiological protective barrier around blood vessels in the brain. It prevents most bacteria and harmful substances from entering the brain through the blood. However, when bacterial meningitis occurs, bacteria enter the brain either from the circulation or by direct invasion from neighbouring structures, causing an inflammatory response that in severe cases may lead to death. High morbidity and mortality are prominent features of the disease. Many pathogenic bacteria can break through the blood-brain barrier and cause meningitis, such as Streptococcus pneumoniae, Group B Streptococcus, Streptococcus suis, Neisseria meningitidis, meningitis-associated Escherichia coli, etc. This article reviews the mechanisms by which these bacteria cross the blood-brain barrier when causing meningitis and the interactions between bacteria and host cells to help pathogens invade the brain. Clarifying the mechanism by which pathogens cross the blood-brain barrier can provide new ideas for developing effective treatments for bacterial meningitis.

Avian pathogenic Escherichia coli (APEC), a significant virulence reservoir for human extraintestinal pathogenic E. coli (ExPEC), poses an escalating zoonotic risk through the food chain. Our previous study demonstrated that the poultry-derived strain DE205B shared high genetic similarity with the neonatal meningitis-associated E. coli (NMEC) strain RS218 and induced meningitis in a rat model. Here, we further demonstrated that DE205B crossed the blood-brain barrier (BBB) via a transcellular pathway without compromising barrier integrity. During this process, brain microvascular endothelial cells (BMECs) trigger limited RIPK1-independent apoptosis. Mechanistically, caspase-8 activation in BMECs drove the release of proinflammatory mediators, thereby promoting neutrophil recruitment into the cerebrospinal fluid (CSF). These neutrophils facilitated bacterial clearance through the formation of neutrophil extracellular traps (NETs). In vivo pharmacological inhibition of caspase-8 attenuated the ability of BMECs to recruit neutrophils, exacerbating meningitis progression. These findings suggested that limited apoptosis of BMECs contributed positively to APEC clearance in the brain. Collectively, this study systematically elucidated mechanisms underlying DE205B-mediated BBB invasion and host immune responses, providing insights into its cross-species pathogenic potential and zoonotic implications.

The risk of lumbar puncture (LP) to precipitate brain herniation in acute bacterial meningitis (ABM) was reviewed in this journal in 2007. We report the case of an infant with ABM who had acute apnea requiring intubation and tonic posturing (mistaken for seizure), and then had brain herniation within four hours of an LP. The case prompted this updated narrative review, from 2007 to 2024, focused on the twelve points made in 2007. The review included 14 case reports of brain herniation shortly after LP in ABM, 23 observational studies or systematic reviews, 28 narrative reviews, and 9 guidelines, each with evidence, advice, or recommendations important for the decision to perform LP in ABM. We found evidence to support, and did not find convincing evidence to refute, the twelve points. We found five additional claims made that were meant to refute some of the original points; however, these were based upon data that did not support the claims made. Limitation of the evidence reviewed was the absence of randomized trials to prove whether those patients who herniated may have been destined to herniate regardless of whether they had an LP. Reasons why ABM may be a unique circumstance where normal CT scan cannot determine the risk of herniation after an LP were discussed. We argue that the preponderance of evidence supported the conclusion that, in a patient with strongly suspected ABM who is clinically considered at high risk for herniation, interventions to control ICP and antibiotics administration should be the priority, followed secondarily by an urgent CT scan and, even with a normal CT, not an LP. The case report emphasized that respiratory arrest or suspected tonic seizure can be due to early herniation, and indicate CT scan, and prolonged LP deferral (for 3-4 days) even with a normal CT.

This systematic review aims to consolidate evidence on the potential of heparin-binding protein (HBP) as an emerging and promising biomarker for diagnosing bacterial meningitis (BM). We conducted a comprehensive search across PubMed, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases, with no restrictions on publication date or language. Sixteen studies, encompassing a total of 2,032 participants, were included in the analysis. The results consistently demonstrated that HBP expression levels in both cerebrospinal fluid (CSF) and blood are markedly elevated in cases of BM compared to patients with non-central nervous system (CNS) infections or other types of meningitis, such as viral meningitis. The pooled sensitivity estimate for HBP measured in CSF was 0.94 [95% confidence interval (CI), 0.88-0.97], and the specificity was 0.96 [95%CI, 0.90-0.98]. The diagnostic odds ratio (DOR) was calculated as 327 [95%CI, 96-1,110]. According to Fagan's nomogram, an initial probability of 20% for a positive test result increased to 85% following a positive HBP test, while a negative test reduced the probability to just 2%. The diagnostic performance of CSF HBP surpassed that of procalcitonin in detecting BM. Furthermore, in cases where symptoms of CNS infection are present, HBP levels in blood also demonstrate notable diagnostic accuracy. These findings suggest that HBP holds significant potential as a biomarker for BM. However, further large-scale studies are required to establish optimal HBP thresholds for improved clinical applicability.

Corticosteroids are ubiquitous endogenous compounds that are essential for most body functions. Exogenous steroids are routinely used for a plethora of conditions associated with substantial and sometimes detrimental inflammation or immune-mediated tissue destruction. In this article, we will review the relevant physiology of steroids, pharmacology of the common exogenously administered steroids, common side effects of glucocorticoid administration, as well as some of the more controversial and less researched indications for steroid therapy in veterinary medicine. Relevant human literature as well as available information on veterinary species will be presented to augment the discussion.

Acanthamoeba keratitis (AK) is a severe infectious disease that causes serious visual impairment and low quality of life. This study aims to investigate the immune landscape in AK, with the goal of improving treatment outcomes through immunotherapy.

We conducted single-cell transcriptome sequencing on corneal tissues from nine patients (3 AK patients, 3 patients with fungal keratitis and 3 patients with bacterial keratitis). Bioinformatic analysis calculated the cell subsets and their proportions within different infectious keratitis. CellChat analysis elucidated the differential expression of chemokines in keratitis. After that, screening amebic nano-antibodies, synthesizing antibody-chemokine fusion proteins, and validated their affinity and chemotactic abilities in vitro and in vivo. And assessing of the therapeutic efficacy of antibody-chemokine fusion proteins.

The UMAP plot demonstrated the 13 major cell clusters in infectious keratitis. Compared with non-AK group, the neutrophil proportion of AK group is markedly reduced. Cell communication indicated a diminished CXCL pathway in AK. Acanthamoeba-specific antibodies were obtained by screening a natural antibody library derived from alpacas. The amoeba-specific antibodies were conjugated with the CXCL1 chemokine, and this fusion protein exhibited robust binding affinity to Acanthamoeba and chemotactic capacity both in vitro and in vivo. Furthermore, in vivo animal investigations indicated that the fusion protein presented excellent therapeutic effect and could effectively eliminate the Acanthamoeba burden.

This study revealed an immune evasion mechanism employed by Acanthamoeba and offered a therapeutic approach. It presents promising potential for enhancing the treatment of infectious diseases by targeting and overcoming challenges posed by immune evasion.

This work was funded by National Natural Science Foundation of China (grant number 82171017 and 82471041) and the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWD&RPP-MRI, JYY2023-6).

Central nervous system (CNS) diseases present unique clinical challenges characterized by insidious symptom onset, complex pathophysiology with incomplete mechanistic understanding, and substantial difficulties in therapeutic evaluation, thereby these inherent complexities create substantial obstacles for developing effective CNS diseases management strategies. Certain edible and medicinal fungi contain bioactive components, including polysaccharides, triterpenoids, alkaloids, and so on, which have therapeutic promise for CNS diseases. This paper reviews the current research advancements regarding the use of edible and medicinal fungi in the context of CNS diseases, highlighting their advantages as prospective therapeutic options and potential roles in both prevention and treatment. Through a comprehensive analysis of existing studies, the mechanisms and applications of these fungi are elucidated, providing valuable insights for the development of novel pharmaceuticals or functional foods aimed at combating CNS diseases.

Glucocorticoids and intravenous immunoglobulin (IVIG) have been established as the primary therapeutic agents for treating autoimmune encephalitis (AE). Methylprednisolone is the most frequently utilized glucocorticoid; however, the potential advantages of dexamethasone (DEX) in the management of encephalitis have yet to be fully elucidated. This study aimed to assess the efficacy of DEX in combination with IVIG in the treatment of pediatric AE.

This retrospective study included 41 pediatric patients who were diagnosed with AE and were categorized into two groups on the basis of their treatment history. Group A (n = 29) comprised children who initially received immunotherapy at other healthcare institutions but were referred to our hospital for DEX+IVIG treatment because of inadequate response to prior therapies. Group B (n = 12) consisted of children who were administered DEX+IVIG treatment early in the acute phase of AE at our hospital. The therapeutic outcomes of DEX+IVIG treatment in children with nonacute AE (Group A) and acute AE (Group B) were evaluated. The modified Rankin scale (mRS) was used to assess the clinical status of all participants.

Ninety percent of the patients were severely ill prior to DEX+IVIG treatment (mRS = 3.8 ± 1.0). Following treatment, the clinical symptoms of children in both the nonacute stage (Group A) and the acute stage (Group B) significantly improved. At the final follow-up, 90.2% of patients (mRS = 0-2) exhibited a favorable prognosis, with a complete response rate (mRS = 0) of 43.9% and a relapse rate of 2.4%. Children who experienced relapse were treated with DEX+IVIG, leading to a positive outcome. No severe adverse events were observed during treatment. The results of this study indicated that DEX+IVIG is an effective treatment for children with acute, nonacute, and relapsing AE.

DEX+IVIG was shown to be beneficial at the acute, nonacute, sequelae, and recurrence stages of AE.

Nanomaterials with unparalleled physical and chemical attributes have become a cornerstone in the field of nanomedicine delivery. These materials can be engineered into various functionalized nanocarriers, which have become the focus of research. Stimulus-responsive nanodrug delivery systems (SRDDS) stand out as a sophisticated class of nanocarriers that can release drugs in response to environmental cues. Due to the complex pathogenesis and the multifaceted pathological environment of the nervous system, developing accurate and effective drug therapy with low side-effects is a formidable task. In recent years, SRDDS have been widely used in the treatment of neurological diseases. By customizing SRDDS to align with the specific microenvironment of the nervous system tissues or external stimulation, the efficacy of drug delivery can be enhanced. This review provides an in-depth look at the characteristics of the microenvironment of neurological diseases and highlights case studies of SRDDS tailored to treat these disorders based on the unique stimulation criteria of nervous system tissues or external triggers. Additionally, this review provides a comprehensive overview of the progress and future prospects of SRDDS technology in the treatment of neurological diseases, providing valuable guidance for its transition from fundamental research to clinical application.

We explored the role of commensal Neisseria in the emergence of third-generation cephalosporin-resistant N. meningitidis. Cefotaxime resistance-conferring penA795 was prevalent among commensal Neisseria isolates in Shanghai, China, and was acquired by a serogroup C quinolone-resistant sequence type 4821 N. meningitidis, Nm507, causing fulminant meningitis in an unvaccinated 2-year-old child.

We investigated the relationship between cerebrospinal fluid (CSF) PCR cycle threshold (Ct) values, clinical characteristics, and outcomes in suspected CAM, while assessing QIAstat-Dx® ME Panel concordance with routine diagnostic methods.

Frozen CSF from 30 individuals with suspected CAM were analyzed using the QIAstat-Dx® ME Panel. Ct values were categorized as low (≤ 30) or high (>30). Concordance with CSF FilmArray®/culture results was assessed using the Kappa coefficient.

Low Ct values were associated to CSF markers of meningitis and predicted ICU admissions (log-rank P = 0.025), particularly within the first two weeks of hospitalization (85 % for low Ct values versus 50 % for high Ct values, P = 0.041). Ct values were not associated with mortality in the survival analysis (log-rank P = 0.109). Substantial agreement was observed between QIAstat-Dx® and comparators (96.7 %, Kappa 0.839).

CSF Ct values can assist in risk stratification for timely ICU admission in individuals with CAM.

Meningitis is an inflammation of the protective membranes surrounding the brain and spinal cord, typically caused by viral or bacterial infections. Bacterial meningitis is a medical emergency requiring prompt diagnosis and treatment, which is associated with a significant mortality rate, even with optimal care. We report the case of a previously healthy 57-year-old man who presented to the emergency department with a three-week history of fever, dry cough, myalgia, fatigue, weakness, anorexia, and excessive sweating. Physical examination revealed a tympanic temperature of 38.9ºC, leukocytosis with neutrophilia, and elevated C-reactive protein levels. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed consolidations in the left lung with air bronchograms and ground-glass opacities. His condition rapidly deteriorated with progressively higher fever, neck stiffness, positive Kernig and Brudzinski signs, profuse sweating, and altered mental status with a Glasgow Coma Scale (GCS) of 8, requiring non-invasive ventilation. He was thus admitted to the intensive care unit (ICU) on the second day of hospitalization. Lumbar puncture confirmed Streptococcus pneumoniae in the cerebrospinal fluid culture, supporting the diagnosis of pneumococcal meningitis. Electroencephalogram (EEG) findings were consistent with severe encephalopathy, while a follow-up CT scan revealed bilateral temporal hypodensities extending into the brainstem, suggestive of ischemic lesions of a vasculitic nature. Magnetic resonance imaging (MRI) confirmed multiple acute ischemic lesions throughout the brain and brainstem, along with signs of leptomeningitis and purulent collections in the lateral ventricles. Despite receiving 14 days of antibiotic therapy and intensive medical efforts, the patient showed no clinical improvement and ultimately succumbed to the infection. This case highlights the critical importance of early recognition and diagnosis of meningitis, as delayed treatment can lead to devastating outcomes. Continuous monitoring and a low threshold of suspicion are key elements for preventing fulminant central nervous system infections.

Redundant and low-value cerebrospinal fluid analysis for suspected meningitis can increase costs and antimicrobial use. Our diagnostic stewardship intervention limited available infectious disease cerebrospinal fluid assays to seven common tests, including a multiplex polymerase chain reaction panel. There was no significant difference in the cost of testing or clinical outcomes.

Meningitis, characterized by an inflammatory response affecting the membranes surrounding the brain and spinal cord, poses a formidable challenge to global public health. Its etiology spans a spectrum of infectious agents, ranging from bacteria, to viruses, fungi, and parasites. Concurrently, mitochondria-traditionally known as 'cellular powerhouses'-have emerged as critical players in various essential biological functions, including but not limited to, energy production, metabolic regulation, and cell fate determination. Emerging evidence suggests that mitochondria may play vital roles in the pathogenesis of meningitis. In this review, we delineated the definition, classification, etiology, pathogenesis, and clinical manifestations of meningitis, and elucidated the structure, dynamics and functions of mitochondria. We subsequently delved into the intricate interplay between meningitis and mitochondria, identifying potential therapeutic interventions targeting mitochondria for the first time. With clinical trials on the horizon, our review lays the foundation for a transformative era in meningitis therapeutics, where unraveling the intricate interplay between meningitis and mitochondria offers promise for mitigating neuroinflammation and improving patient outcomes.

The BioFire FilmArray meningitis/encephalitis panel (MEP) was brought to the University of Kentucky in 2016 to aid in the identification of community-acquired meningitis and encephalitis (ME). This panel has shown variable performance with some institutions showing high sensitivity and specificity for many pathogens but others seeing false positives during clinical use. We evaluated the panel's performance using retrospective chart review of patients at the University of Kentucky from October 2016 to September 2022, including 7,551 MEP results. Cerebrospinal fluid (CSF) samples with positive results for bacterial and fungal pathogens were compared with CSF and blood cultures, other laboratory parameters, and clinical presentations, to classify MEP results as true positive (TP), likely TP, or false positive (FP). Of 132 patients with positive bacterial or fungal MEP results, 48.9% of bacterial and 88.9% of cryptococcal analytes were classified as TP. The positive predictive value (PPV) varied by organism, with the highest being Listeria monocytogenes and Neisseria meningitidis. One-third of the FP results were Streptococcus agalactiae. Among patients with likely TP, 75.7% (28 out of 37) received oral or IV antibiotics before blood or CSF culture. MEP was 100% specific compared to culture. The PPV based on pathogen ranged from 78.6% to 100%. Interestingly, 27.4% (29 out of 106) cases (excluding FPs) would have no pathogen definitively identified if MEP had not been used. This study highlights the utility of MEP in rapidly diagnosing ME, particularly in patients pretreated with antibiotics. It also emphasizes the importance of correlating MEP results with clinical assessments and other diagnostic tests to assure accuracy.

This study compares the performance of the meningitis/encephalitis panel (MEP) in detecting bacterial and fungal pathogens with cerebrospinal fluid cultures and other parameters. Almost half of bacterial analytes of MEP had positive cerebrospinal fluid (CSF) or blood cultures; the remaining 42% of bacterial analytes were correlated with clinical presentation and other CSF parameters. 27.4% (29 out of 106) cases would not have had a pathogen definitively identified if the MEP had not been used. This study highlights the importance of using MEP as a diagnostic tool, especially in patients who have already received antibiotics, where traditional culture-based methods may not be diagnostic. This research underscores the use of MEP in improving the speed of diagnosing meningitis. However, it emphasizes that MEP can produce false positive results in some patients. It is therefore necessary to interpret MEP results together with clinical assessments and other diagnostic tests to ensure the most accurate diagnosis.

In clinical practice, antibiotics have historically been utilized for the treatment of pathogenic bacteria. However, the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach. In 2022, Escherichia coli, a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence, emerged as the predominant pathogenic bacterium in China. The rapid emergence of antibiotic-resistant E. coli strains has rendered antibiotics insufficient to fight E. coli infections. Traditional Chinese medicine (TCM) has made remarkable contributions to the health of Chinese people for thousands of years, and its significant therapeutic effects have been proven in clinical practice. In this paper, we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E. coli infections. First of all, this review introduces the classification, antibiotic resistance characteristics and mechanisms of E. coli. Then, the TCM formulas and extracts are listed along with their active ingredients against E. coli, including extraction solution, minimum inhibitory concentration (MIC), and the antibacterial mechanisms. In addition, there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E. coli infections, and we provide a summary of this evidence and its underlying mechanisms. In conclusion, we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E. coli infections. We hold the opinion that TCM will play an important role in global health, pharmaceutical development, and livestock farming in the future.

In young children, pneumococcal meningitis epitomizes the paradigm of a destructive innate inflammatory response in the central nervous system: a five-alarm fire. In contrast, cell-free bacterial components reaching the fetal brain from an infected mother signal a quiet, noninflammatory immune response that drives abnormal neurodevelopment, changing brain architecture through neuroproliferation. This review addresses the difference between prenatal and postnatal bacterial-host signaling within the brain.

Early detection of bovine mastitis-causing pathogens is necessary for treatment. As culturing methods are time-consuming, a more rapid detection technique is required. This study investigated the sensitivity, specificity, and detection limit of Gram staining of milk precipitates (milk Gram stain, MGS) to detect bovine mastitis-causing pathogens in milk, as well as the potential of MGS to diagnose inflammation by counting polymorphonuclear leukocytes (PMN). MGS was performed on spontaneous mastitis cases. Culture methods were also used as reference standards to calculate the sensitivity, specificity, and bacterial load in milk to determine the detection limit of MGS. PMN in the mastitic milk were counted using Gram staining. Further, somatic cell counts (SCC), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-10 and serum amyloid A (SAA) concentrations in mastitic milk were measured using cell counting and enzyme-linked immunosorbent assay. The sensitivity and specificity for all pathogens were 0.62 and 0.90, for Gram-positive were 0.67 and 0.90, and for Gram-negative were 0.50 and 1.00, respectively. The detection limits for Gram-positive and Gram-negative bacteria were 1,560 and 4,680 cfu/mL, respectively. SCC were significantly positively correlated with PMN, milk IL-6, TNF-α, and SAA concentrations, whereas PMN were significantly negatively correlated with milk IL-10 concentration. Our results suggest that MGS may be applied as a rapid method to identify causal pathogens of mastitis before culture results are determined and may also estimate inflammatory status which cannot be detected with SCC. Further clinical trials are required to elucidate whether MGS is useful in clinical veterinary settings.

Evidence regarding the host's response to peripheral pathogens in humans abound, whereas studies on the pathogenesis of central nervous system-penetrating infections are relatively scarce. However, given the spate of epidemic and pandemic neuroinfections in the 21st century, the field has experienced a renewed interest lately. This chapter discusses a timely and exciting topic on the roles of glial cells, mainly microglia and astrocytes, in neuroinvasive infections. This chapter considered fungal, viral, and bacterial neuroinfections, X-raying their neuroinvasiveness, neurotropism, and neurovirulence before focusing on specific examples notable for each category, including Escherichia coli, Cryptococcus neoformans, and SARS-CoV-2. These infections are renowned worldwide for a high case-fatality rate, leaving many survivors with life-long morbidity and others with a bleak future neurologic prognosis. Importantly, the chapter discusses possible ways microglia and astrocytes are culpable in these infections and provides approaches by which they can be manipulated for therapeutic purposes, identifying viable research gaps in the process. Additionally, it offers a synopsis of ongoing works considering microglial selective targeting to attenuate the pathology, morbidity, and mortality associated with these neuroinfections. Considering that microglia and astrocytes are first responders in the central nervous system, targeting these glial cells could be the game changer in managing existing and emerging neuroinvasive infections.

Cochlear implants (CIs) are associated with a range of infections. These infections present unique considerations because of their position relative to the respiratory tract and the central nervous system, as well as the propensity for biofilms to form on CIs. This article reviews infections related to CIs, including otitis media, mastoiditis, meningitis, and deep CI infection. High-quality evidence on the prevention and management of CI infections is lacking; however, best practices regarding prevention and management are provided.

The accurate and sensitive diagnosis of intracranial infection continues to pose a critical challenge. This study aimed to probe into the clinical value of heparin binding protein (HBP) in bacterial intracranial infection.

Patients suspected of having bacterial intracranial infection and admitted to Shanghai General Hospital from November 2021 to November 2023 were selected as study subjects and divided into an infected group and a non-infected group. The receiver operating characteristic (ROC) curve was constructed to compare the diagnostic accuracy of HBP, procalcitonin (PCT), and C-reactive protein (CRP), as well as their value in differentiating Gram-positive bacteria and Gram-negative bacterial infections.

According to the results of bacterial identification, the infected groups were divided into a Gram-negative bacteria group (n = 142) and a Gram-positive bacteria group (n = 128), while the non-infected group comprised 120 patients after neurosurgery involving dura opening. Statistically significant differences were observed in the levels of HBP, PCT, and CRP between the infected group and the non-infected group (all p< 0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of HBP was 0.935, and the AUCs of PCT and CRP were 0.931 and 0.863, respectively. In the comparison of HBP, PCT, and CRP levels in the Gram-negative bacteria and Gram-positive bacteria groups, the AUCs were 0.816, 0.602, and 0.591, respectively. When the cutoff value of HBP was 72.34 ng/mL, its specificity reached 96.1% and its sensitivity was 57.8%. When PCT and CRP levels were less than 1.67 ng/mL and 23.12 ng/mL, respectively, both the sensitivity (52.3%, 53.1%) and specificity (66.9%, 59.9%) were relatively low.

HBP, PCT, and CRP can be employed as diagnostic indicators for bacterial intracranial infection. HBP (>72.34 ng/mL) can act as an important index for the diagnosis of Gram-negative bacteria in patients with intracranial infection.

Fever is a common condition in intensive care unit (ICU) patients, with an incidence between 30 and 50% in non-neurological ICU patients and up to 70-90% in neurological ICU patients. We aim to perform systematic review and meta-analysis of current literature to assess impact of fever on neurological outcomes and mortality of acute brain injury patients.

We searched PubMed/Medline, Scopus and Embase databases following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and we included both retrospective and prospective observational studies, interventional studies, and randomized clinical trials that had data on body temperature and fever during ICU admission. The primary endpoints were neurological outcome and mortality at any time. Secondary outcomes included: early neurological deterioration, delayed cerebral ischemia (DCI, only for patients with subarachnoid hemorrhage), large infarct or hemorrhage size, hemorrhagic transformation (only for patients with ischemic stroke). This study was registered in PROSPERO (CRD42020155903).

180 studies from 14692 records identified after the initial search were included in the final analysis, for a total of 460,825 patients. Fever was associated with an increased probability of unfavorable neurological outcome (pooled OR 2.37 [95% CI 2.08-2.71], I2:92%), death (pooled OR 1.31 [95% CI 1.28-1.34], I2:93%), neurological deterioration (pooled OR 1.10 [95% CI 1.05-1.15]), risk of DCI (pooled OR 1.96 [95% CI 1.73-2.22]), large infarct size (pooled OR 2.94 [95% CI 2.90-2.98]) and hemorrhagic transformation (pooled OR 1.63 [95% CI 1.34-1.97]) and large hemorrhagic volume (pooled OR 2.38 [95% CI 1.94-2.93]).

Fever was associated with poor neurological outcomes and mortality in patients with acute brain injury. Whether normothermia should be targeted in the management of all neuro critically ill patients warrants specific research.

Guidelines for bacterial meningitis in children recommend intravenous ceftriaxone 50 mg/kg (max 2 g) twice daily (BD) or 100 mg/kg (max 4 g) once daily (OD), leaving the decision regarding the dose frequency to the prescriber. We investigated the cerebrospinal fluid (CSF) penetration of ceftriaxone to evaluate whether one dosing regimen is superior. Unbound ceftriaxone concentrations were measured in serum and CSF samples from children aged 0-18 years treated with ceftriaxone if there was a sample remaining after clinical tests were performed. A serum-CSF population pharmacokinetic model was developed using non-linear mixed-effects modeling. The once- and twice-daily dosing regimens were simulated, and the probability of target attainment (PTA) was determined for maintaining a CSF concentration above a minimum inhibitory concentration (MIC) of 1 mg/L for common meningitis pathogens and 4 mg/L for Staphylococcus aureus for 100% of the dosing interval. Sixteen serum and 87 CSF samples were collected from 98 children (age range 0.1-18.5 years). The final two-compartment serum-CSF model included a renal maturation function with weight scaling on clearance and volume of distribution. The estimated serum:CSF uptake was 20.1%. For MIC 1 mg/L, the 24 h PTA was higher for OD (88%) compared with BD (53%) dosing, although both achieved a 100% PTA at steady state. For S. aureus (MIC 4 mg/L), neither dosing regimen was sufficient. Our findings support the use of a 100 mg/kg once daily regimen for empirical treatment of bacterial meningitis due to earlier achievement of the pharmacodynamic target. Neither dosing regimen was adequate for S. aureus meningitis.

Identifying the responsible pathogen is crucial for precision medicine in intracranial infections, and Cerebrospinal Fluid (CSF) Metagenomic Next-Generation Sequencing (mNGS) is a reliable method for this detection. However, the indiscriminate utilization of this approach may impose a financial burden on both patients and society. The study aims to investigate the optimal conditions for applying CSF mNGS in patients with suspected intracranial infections, offering valuable references for precision medicine of intracranial infections.

A total of 175 hospitalized patients presenting with suspected intracranial infections were selected for retrospective analysis. Base on the detection of responsible pathogens using CSF mNGS, the patients were categorized into two groups, responsible pathogens in Group A were detected but not in Group B. The types of responsible pathogens in group A and the final diagnosis of patients in group B were analyzed. Demographic data, clinical presentation, CSF analysis, imaging results, and electroencephalography (EEG) findings were analyzed for both groups. Finally, a scoring system was established to promptly assess the appropriateness of CSF mNGS for patients with suspected intracranial infections. Each independent predictor was assigned a score of 1, and the patients were subsequently scored. We advocate sending patients' CSF for mNGS when the cumulative score is ≥ 2.

In Group A, the predominant responsible pathogen was the varicella-zoster virus (VZV), while Group B exhibited the highest proportion of final diagnoses related to epilepsy. The logistic regression model indicates that headache [OR = 2.982, 95% CI (1.204-7.383), p = 0.018], increased cerebrospinal fluid white cell count [OR = 4.022, 95% CI (1.331-12.156), p = 0.014], and decreased cerebrospinal fluid glucose levels [OR = 9.006, 95% CI (2.778-29.194), P < 0.001] are independent predictive factors for intracranial infection pathogens detected by CSF mNGS. Under this scoring system, the sensitivity for detecting the responsible pathogen was 57.5%, and the specificity was 87.4%.

The likelihood of detecting the responsible pathogen through CSF mNGS in patients with suspected intracranial infections can be evaluated using the scoring system. Furthermore, it is crucial to consider the possibility of another condition, such as epilepsy, when the responsible pathogen is not detected using cerebrospinal fluid mNGS.

Streptococcus oralis, belonging to the viridans group streptococci (VGS), has been considered a member of normal flora mainly inhabiting the oral cavity. However, more recently, there has been growing recognition of its role as a causative agent in various life-threatening infectious diseases such as infective endocarditis (IE) and meningitis. Additionally, the differences in the prevalence, clinical features, and prognosis of opportunistic infections between S. oralis and other VGS species have been addressed. Particularly the predominance of S. oralis in IE has drawn critical attention. In potentially fatal infections, clinical neglect of S. oralis as an instigating agent might significantly impede early diagnosis and treatment. Nevertheless, to date, the infectious diseases associated with S. oralis have not yet been comprehensively described. Therefore, this review will give an overview of infectious diseases caused by S. oralis to uncover its hidden role as an opportunistic pathogen.

Our objective was to evaluate the ramifications of the 2019 coronavirus disease (COVID-19) pandemic on the microbial profile and antimicrobial resistance patterns of bacteria isolated from cerebrospinal fluid (CSF) specimens of patients with bacterial meningitis. We conducted a retrospective analysis of laboratory results and clinical records about positive CSF cultures reported by the SPARSS network from 2017 to 2023. The study covered three distinct periods: January 2017 to December 2019 (before the COVID-19 pandemic), January 2020 to December 2022 (during the COVID-19 pandemic), and January 2023 to December 2023 (after the COVID-19 pandemic), with a total of 5793 CSF isolates collected. Notably, the proportion of male patients (61.3%) was higher than that of females. After COVID-19, we observed a notable shift in the seasonal peak of CSF pathogens, with a delay of approximately 3 months. Remarkable alterations were evident in both pediatric and adult CSF isolate profiles. In children, the predominant pathogens included coagulase-negative Staphylococcus (CoNS), Streptococcus pneumonia, and Escherichia coli. Notably. After COVID-19, there was a significant decrease in the proportion of CoNS (p = 0.0039) and a notable increase in E. coli (p = 0.0067). In adults, the top three pathogens were CoNS, Acinetobacter baumannii, and Klebsiella pneumoniae. After the pandemic, we observed a significant reduction in the prevalence of A. baumannii (p = 0.0059), while the proportions of K. pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis increased significantly (p < 0.05). Additionally, among multidrug-resistant bacteria, the detection rate of carbapenem-resistant E. coli escalated (p = 0.0375). Antimicrobial susceptibility analysis indicated a declining trend in resistance rates for CoNS and A. baumannii to certain antibiotics following the pandemic. Conversely, resistance to imipenem in A. baumannii increased. In conclusion, the COVID-19 pandemic has significantly influenced the composition, antimicrobial resistance patterns, and epidemiological dynamics of CSF-isolated bacteria in Shandong province. To effectively address these changes, ongoing and dynamic surveillance of pathogen trends and antimicrobial resistance rate is essential.

Cerebrospinal fluid (CSF) analysis is the gold standard for meningitis diagnosis. It is invasive, time-consuming, and can inoculate infection. CSF analysis is not appropriate for many children without significant clinical suspicion, and delaying decision-making can have negative consequences. Therefore, medical research has long focused on speedy, non-invasive meningitis diagnosis. This study aimed to examine the positive predictive value (PPV) of contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (CE-FLAIR MRI) in meningitis diagnosis.

It was a cross-sectional study that was conducted in the Department of Radiology, The Children's Hospital in Lahore, from December 29, 2017, to June 28, 2018. The 198 patients were included of either gender with an age of 1 to 15 years and underwent CE-FLAIR MRI due to suspicion of meningitis. The gold standard for meningitis diagnosis was cerebrospinal fluid analysis, while CE-FLAIR MRI results were graded as true positives and false positives. The chi-square test was used. The p-value less than 0.05 was taken as statistically significant.

The mean age of the patients was 4.18±2.48 years. The majority, 116 (58.6%), of the patients were aged below 5 years. There were 125 (63.1%) male and 73 (36.9%) female patients with a male-to-female ratio of 1.7:1. The diagnosis of meningitis using CE-FLAIR MRI was made in 187 (94.4%) patients with a PPV of 94.4%, which was further confirmed on CSF analysis. The PPV of CE-FLAIR-MRI across various subgroups based on the patient's age and gender were statistically insignificant, which showed consistency across all included age and gender groups (p > 0.05).

The contrast-enhanced FLAIR magnetic resonance imaging was found to have a high positive predictive value of 94.4% in the diagnosis of meningitis, taking cerebrospinal fluid analysis as the gold standard. CE-FLAIR MRI's noninvasive and ionizing radiation-free characteristics advocate its preferred use in future clinical practice.

Streptococcus species represent a significant global cause of meningitis, leading to brain damage through bacterial virulence factors and the host inflammatory response. Upon entering the central nervous system (CNS), excessive inflammation leads to various neurological and psychological complications. This review explores the pathophysiological mechanisms and associated outcomes of streptococcal meningitis, particularly its short- and long-term neurological sequelae. Neurological symptoms, such as cognitive impairment, motor deficits, and sensory loss, are shown to vary in severity, with children being particularly susceptible to lasting complications. Among survivors, hearing loss, cognitive decline, and cranial nerve palsies emerge as the most frequently reported complications. The findings highlight the need for timely intervention, including neurorehabilitation strategies that focus on optimizing recovery and mitigating long-term disabilities. Future recommendations emphasize improving early diagnosis, expanding vaccine access, and personalizing rehabilitation protocols to enhance patient outcomes. As a novel contribution, this review proposes the term "post-meningitic syndrome" to showcase the broad spectrum of CNS complications that persist following streptococcal meningitis, providing a framework for a future clinical and research focus.

Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls.

A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2-3, 5-7, and 10-15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t-tests, Chi-square tests, and generalized mixed models.

We included 110 patients-43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH-interventional (p = 0.003) and versus the control (p = 0.004), as well as at timepoint 2 for ICH versus SAH-interventional (p = 0.002) and versus SAH-surgical (p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine.

In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase.

Meningococcal meningitis is still a severe disease causing high mortality and morbidity rates. Early diagnosis is crucial to ensure prompt antibiotic therapy. However, identification of the pathogen can be challenging.

A 32-year-old male patient with systemic lupus erythematosus (SLE) presented to the emergency room with fever, nausea, vomiting, headache and lower back pain as well as multiple petechial bleedings. On suspicion of meningococcal infection, the emergency doctor had already administered one dose of ceftriaxone before arrival to the clinic. Blood works showed massive inflammation due to bacterial infection. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and glucose levels but PCR was positive for Neisseria meningitis and IL-6 as well as IL-8 were elevated. On antibiotic therapy with ceftriaxone, the patient's condition improved quickly.

We present a rare case of meningococcal infection of the CSF in a SLE patient without further CSF abnormalities. We discuss the involvement of early antibiotic treatment and the role of the patient's immune status in the normal CSF findings of this case. Moreover, this case demonstrates the importance of early antibiotic therapy in bacterial meningitis for the clinical outcome.

We present a case of a 60-year-old woman who developed invasive group A streptococcal (GAS) meningitis following a COVID-19 infection, complicated by multisystem inflammatory syndrome (MIS). Initially diagnosed with COVID-19 based on fever, nasal obstruction, cough, and sore throat, her symptoms improved with symptomatic treatment, except for a persistent sore throat. She later presented with hematemesis and was found to have bacterial pneumonia and dehydration. Despite treatment with ceftriaxone, her condition worsened with the development of a headache, shivering, and worsening respiratory and circulatory symptoms. Cerebrospinal fluid analysis confirmed bacterial meningitis, and treatment was escalated to include ceftriaxone, ampicillin, and vancomycin. An MRI revealed a parapharyngeal space abscess, and subsequent blood cultures identified GAS as the causative organism. The patient was treated with ampicillin for 14 days, followed by oral amoxicillin. Her condition improved, and she was discharged with no neurological deficits. This case underscores the need for vigilance in detecting secondary bacterial infections in post-COVID-19 patients, especially in MIS, where atypical presentations can delay diagnosis. Early recognition and aggressive treatment are vital to preventing complications and ensuring favorable outcomes.

Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy.

Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI.

By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections.

Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts.

Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood-brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P < 0.001). NF-κB signaling was found to contribute to the production of chemokines such as TNF-1α, IL-β, and IL-6. Additionally, transmission electron microscopy revealed that paracellular migration might be the strategy employed by P. multocida to cross the BBB. This study provides the first evidence of the migration strategy used by P. multocida to traverse the mammalian BBB. The data presented herein will contribute to a better understanding of the pathogenesis of the zoonotic pathogen P. multocida.

Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.

We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.

The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p<0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).

Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.

The primary obstacles in the management of Enterococcus and Streptococcal infections are drug resistance and biofilm formation. Our study revealed that loratadine at a concentration of ≥25 μM exhibited significant inhibitory effects on biofilm formation in 167 clinical strains of Enterococcus faecalis and 15 clinical isolates of Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus pneumoniae. Additionally, the antibiofilm activity against E. faecalis and Streptococcal was demonstrated by several loratadine derivatives with altered side-chain carbamate moieties. This study investigated the antibacterial activity of the loratadine derivative Lo-7 against clinical strains of S. agalactiae and S. pyogenes, with minimum inhibitory concentrations ranging from 12.5 to 25 μM. The findings revealed that a low concentration of loratadine derivative Lo-7 (3.125 μM) significantly augmented the bactericidal efficacy of vancomycin against multidrug-resistant (MDR) S. agalactiae, both in vitro and in vivo. The loratadine derivative Lo-7, even at low concentrations, demonstrated significant efficacy in eliminating intracellular MDR S. agalactiae within macrophages, potentially indicating a unique advantage over vancomycin, linezolid, and loratadine. Mechanistically, exposure to the loratadine derivative Lo-7 resulted in membrane depolarization without affecting membrane permeability in S. agalactiae. The potential targeting of the SecG subunit of the SecYEG membrane-embedded channel by the loratadine derivative Lo-7 in S. agalactiae was identified through quantitative proteomics, a drug affinity responsive target stability assay, and molecular docking.

There is compelling evidence that a dysregulated immune inflammatory response in neuroinfectious diseases results in modifications in metabolic processes and altered metabolites, directly or indirectly influencing lipid metabolism within the central nervous system (CNS). The challenges in differential diagnosis and the provision of effective treatment in many neuroinfectious diseases are, in part, due to limited understanding of the pathophysiology underlying the disease. Although there are numerous metabolomics studies, there remains a deficit in neurolipidomics research to provide a comprehensive understanding of the connection between altered metabolites and changes in lipid metabolism. The brain is an inherently high-lipid organ; hence, understanding neurolipidomics is the key to future breakthroughs. This review aims to provide an integrative summary of altered cerebrospinal fluid (CSF) metabolites associated with neurolipid metabolism in bacterial and viral CNS infections, with a particular focus on studies that used liquid chromatography-mass spectrometry (LC-MS). Lipid components (phospholipids) and metabolites (carnitine and tryptophan) appear to be the most significant indicators in both bacterial and viral infections. On the basis of our analysis of the literature, we recommend employing neurolipidomics in conjunction with existing neurometabolomics data as a prospective method to enhance our understanding of the cross link between dysregulated metabolites and lipid metabolism in neuroinfectious diseases.

Listeria monocytogenes (LM) is an important foodborne bacterium, and LM meningoencephalitis is rare in clinical practice, with poor prognosis in severe patients. It is prone to misdiagnosis in clinical practice. We first reported a case of severe LM meningoencephalitis with muscle lesions and evaluated the comprehensive condition.

A 48-year-old man had a fever and was admitted to the neurology department due to dizziness, nausea, and vomiting for 20 days.

LM meningoencephalitis complicated with muscle lesions.

We used moxifloxacin 0.4 g, qd, meropenem 2 g, q8h, and dexamethasone 10 mg, qd to reduce exudation and adhesion. Then due to consideration of side effects, we increased the dose of ampicillin by 2 g, q4h, stopped using meropenem and moxifloxacin, and turned to maintenance treatment with dexamethasone and ampicillin. We comprehensively managed his vital signs and physical organ functions, we also controlled some comorbidities. During the hospitalization period thereafter, we used intravenous anti-infection treatment with moxifloxacin 0.4 g, qd, ampicillin 0.5 g, q4h.

Half a year later, the reexamination showed only protein elevation in cerebrospinal fluid and hydrocephalus in MRI. Afterward, the symptoms did not recur again. The patient recovered well after discharge.

LM meningoencephalitis complicated with lower limb muscle lesions is clinically rare. This report focuses on relevant treatment plans, which provide value for the examination and comprehensive management of patients with LM infection in the future.

Central nervous system infections are due to different microorganisms such as viruses, bacteria, mycobacteria, fungi, amoebas, and other parasites. The etiology depends on multiple risk factors, and it defines the infection location because some microorganisms prefer meninges, brain tissue, cerebellum, brain stem or spinal cord. The microorganisms induce diseases in the nervous system through direct invasion, neurotoxin production, and the triggered immune response. To determine the infection etiology, there are several diagnostic tests which may be conducted with cerebrospinal fluid, blood, respiratory and stool samples. These tests include but are not limited to direct microscopic examination of the sample, stains, cultures, antigenic tests, nucleic acid amplification tests, metagenomic next-generation sequencing, immunologic biomarker and neuroimaging, especially contrast-enhanced magnetic resonance imaging. The treatment may consist of specific antimicrobial treatment and supportive standard care. Since viruses have no specific antiviral treatment, antimicrobial treatment is mainly targeted at non-viral infections. This article will focus on diagnosis and treatment of acute acquired infections of the central nervous system beyond the neonatal period. The discussion defines the disease, provides the clinical presentation, explains the etiology and risk factors, and briefly mentions potential complications. This updated review aims to provide the reader with all the elements needed to adequately approach a patient with a central nervous system infection. Mycobacterium tuberculosis infection, Cryptococcus spp. infection and vaccines are not within the scope of this article.

Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear.

The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV).

The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences.

A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2 years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant.

AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2 years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.

A first psychotic episode may be related to neurological diseases, especially encephalitis of infectious or autoimmune origin. It is remarkable that an immune-mediated encephalitis triggered by a confirmed subacute bacterial meningitis is documented, and this is the case we will present.

A 22-year-old woman with no previous medical history, immunocompetent, with three months of behavioral, affective and cognitive symptoms with subsequent compromise of sensory perception and psychosis. Examination of cerebrospinal fluid showed inflammatory signs with positive FilmArray© for Streptococcus pneumoniae. She received anti-psychotic and antibiotic treatment for 2 weeks without clinical improvement. Postencephalitic syndrome with immune-mediated psychosis was considered as a diagnosis, and immunosuppressive management with corticosteroid and plasmapheresis was initiated with complete resolution of symptoms. After one year of follow-up no neurological relapse has been identified.

Encephalitis is a neurological syndrome due to brain parenchymal damage that can result in psychiatric symptoms including psychosis and behavioral changes. Its causes are usually infectious (usually viral) or autoimmune (Anti NMDA, AMPA, LGI1 or others). A psychiatric condition in bacterial meningitis without improvement with antibiotic treatment is remarkable, its presence should suggest an immune-mediated post-infectious syndrome that may respond to the use of immunomodulators even in the absence of identification of autoimmune encephalitis-associated antibodies. No similar cases have been reported in the literature.

Immune-mediated psychosis may be a manifestation of post-encephalitic syndrome associated with bacterial meningitis and its treatment with immunosuppressants may offer benefit in cases where the use of antipsychotics and antibiotics shows no improvement.