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Listeria monocytogenes is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which L. monocytogenes and other pathogens traffic to the brain have been studied, a quantitative understanding of the underlying dynamics of colonization and replication within the brain is still lacking. In this study, we used barcoded L. monocytogenes to quantify the bottlenecks and dissemination patterns that lead to cerebral infection. Following intravenous (IV) inoculation, multiple independent invasion events seeded all parts of the CNS from the blood, however, only one clone usually became dominant in the brain. Sequential IV inoculations and intracranial inoculations suggested that clones that had a temporal advantage (i.e., seeded the CNS first), rather than a spatial advantage (i.e., invaded a particular brain region), were the main drivers of clonal dominance. In a foodborne model of cerebral infection with immunocompromised mice, rare invasion events instead led to a highly infected yet monoclonal CNS. This restrictive bottleneck likely arose from pathogen transit into the blood, rather than directly from the blood to the brain. Collectively, our findings provide a detailed quantitative understanding of the L. monocytogenes population dynamics that lead to CNS infection and a framework for studying the dynamics of other cerebral infections.

Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans, the severity of which depends on multiple factors, including intrinsic characteristics of the affected individuals and the pathogen itself. Additionally, emerging evidence suggests that epigenetic modifications may also modulate host susceptibility to infection. Therefore, different clinical outcomes can be expected, ranging from self-limiting gastroenteritis to severe central nervous system and maternal-neonatal infections, and bacteremia. Furthermore, L. monocytogenes is a genetically and phenotypically diverse species, resulting in a large variation in virulence potential between strains. Multilocus sequence typing (MLST) has been widely used to categorize the clonal structure of bacterial species and to define clonal complexes (CCs) of genetically related isolates. The combination of MLST and epidemiological data allows to distinguish hypervirulent CCs, which are notably more prevalent in clinical cases and typically associated with severe forms of the disease. Conversely, other CCs, termed hypovirulent, are predominantly isolated from food and food processing environments and are associated with the occurrence of listeriosis in immunosuppressed individuals. Reports of genetic traits associated with this diversity have been described. The Food and Agriculture Organization (FAO) is encouraging the search for virulence biomarkers to rapidly identify the main strains of concern to reduce food waste and economical losses. The aim of this review is to comprehensively collect, describe and discuss the methodologies used to discriminate the virulence potential of L. monocytogenes CCs. From the exploration of in vitro and in vivo models to the study of expression of virulence genes, each approach is critically explored to better understand its applicability and efficiency in distinguishing the virulence potential of the pathogen. [ABSTRACT FROM AUTHOR]

Background: Lyme borreliosis is by far the most common vector-borne infection in Western Europe. The most severe manifestation of Lyme borreliosis is Lyme neuroborreliosis (LNB). In LNB symptoms vary from mild to severe and may include late complications that involve both physical and/or neurocognitive constraints. An estimated 25–28% of the LNB population suffers from late complications. This study investigates patient and relative perspectives on everyday life with LNB symptoms, diagnosis, and treatment to identify areas for improvement of healthcare. Methods: A focus group was conducted at Odense University Hospital, Denmark. The focus group comprised 16 participants, nine patients diagnosed with LNB who had been treated at the Clinical Center for Emerging and Vector-borne Infections, and seven relatives of the patients' choice. The focus group lasted 2 ½ hours and was audio recorded as well as documented in field notes. Results: Data analysis was grounded in the conceptual framework of critical psychology and resulted in three main themes: (1) Burden of LNB symptoms in everyday life, (2) A break in the conduct of everyday life caused by LNB and (3) Need for transparent pathways to specialist knowledge. Conclusions: Before diagnosis and treatment, each patient reported varying degrees of non-treatable pain, and cognitive and/or musculoskeletal symptoms. Visible physical symptoms were rare. All patients had experienced that their bodily symptoms remained unaddressed throughout numerous encounters with the healthcare system. The course of LNB comes with a break in patients' everyday lives and self-understandings affecting their ability to work and manage everyday activities. Patients and relatives strongly recommend a specialised LNB clinic. [ABSTRACT FROM AUTHOR]

Neonates admitted to the intensive care unit are at risk of brain injury. Importantly, infants with signs of neurological impairment need prompt diagnosis to guide intervention. Cranial ultrasound (CUS) is the first‐line imaging tool for infants born preterm. New developments in this technology, which now incorporates high‐resolution equipment, have notably improved the performance of CUS in infants born at term and near‐term. On the other hand, the potential of CUS as a diagnostic tool in older infants is less established. The lack of studies focusing on this topic, local protocol variability among clinical sites, and divergent opinions on CUS patterns of disease entities are the main constraints. This review provides an overview of state‐of‐the‐art CUS as a decision‐making tool under different clinical scenarios, such as neonatal encephalopathy, seizures, and suspected central nervous system infection. The CUS features that characterize several patterns supporting a diagnosis are detailed, focusing on haemorrhage and infection. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders. Methods: CSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals. Results: Twenty-seven healthy cattle and 86 sick cattle with either CNS infectiousinflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1-2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively. Discussion: This is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Background: Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability. Methods: A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods. Results: Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate. Conclusions: This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities. Key points: Ependymal cells play an important role in the maintenance of CSF homeostasis and CNS health by forming physical and immune barriers against pathogen invasion. PPRs signaling pathways, cilia and intercellular junctions, cytokine secretion or senescence of ependymal cells can lead to dysfunction, which in turn is involved in the onset and progression of CNS infection. We propose potential therapeutic applications including gene transfer and novel biomarkers. Studies of ependymal cells have provided new ideas for pathophysiology and treatment, but further research is needed to fully understand their role in CNS infection and evaluate therapeutic effect. [ABSTRACT FROM AUTHOR]

The treatment of brain abscess induced by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a clinical challenge around the world. Apart from novel blactam/ b-lactamase inhibitors and polymyxins, there are few sufficiently powerful antibiotics that are effective against CRPA-induced infections. Considering the blood-brain barrier factor, there are even fewer drugs that can be used to treat intracranial CRPA-induced infections. In this article, we reported a case of CRPA-induced brain abscess that was successfully treated with intravenous ceftazidime/avibactam and intrathecal colistimethate sodium in a child after intracranial tumor resection. [ABSTRACT FROM AUTHOR]

Introduction: Invasive fungal infections affecting the central nervous system (CNS) are a major health concern worldwide associated with high mortality rates. Their increased incidence is largely due to an increase in the vulnerable immunocompromised population, changing environmental factors, and development of more accurate diagnostic methods. The aim of this article is to identify fungal causes of CNS infections that are recently emerging or have the potential to become emerging pathogens in the near future, as well as their clinical characteristics, including: Candida auris, Trichosporon spp., Blastomyces spp., Sporothrix spp., Talaromyces marneffei, Lomentospora prolificans, and Scedosporium spp. Methods: A review of the literature in PubMed in the last ten years was conducted to identify central nervous system infections caused by each of these fungi. Results: The review identified 10 cases caused by C. auris, 5 cases by Trichosporon spp., 82 cases by Blastomyces spp., 36 cases by Sporothrix spp., 21 cases by T. marneffei, 22 cases by Lomentospora prolificans, and 42 cases by Scedosporium spp. Discussion: The exact burden of these diseases remains difficult to ascertain, but their apparent rise underscores the urgent need for improved diagnostic, treatment, and management strategies against CNS fungal pathogens to improve outcomes against these life-threatening infections. [ABSTRACT FROM AUTHOR]

(1) Background: Central nervous system (CNS) infections, including meningitis and encephalitis, are serious conditions which are associated with high morbidity and mortality. This study aims to identify the clinical manifestations, etiologies, and outcomes of meningitis and encephalitis in adult patients in Saudi Arabia, addressing the current gap in understanding these conditions within this population. (2) Methods: This is a single-center retrospective study which included all adult patients diagnosed with meningitis and encephalitis from March 2016 to May 2022. (3) Results: This study found that most cases of meningitis and encephalitis occurred due to unknown pathogens. Pretreatment with antibiotics prior to lumbar puncture (LP) was found in 71.2% of patients with meningitis. Altered mental status and seizures were common presenting symptoms among patients with encephalitis while altered mental status and fever were common among patients with meningitis. (4) Conclusions: Adherence to guidelines in treating meningitis and encephalitis and performing LPs in a timely manner are important. Establishing national biobanks with biological samples from patients suspected of having meningitis or encephalitis will significantly enhance our understanding of these conditions in Saudi Arabia. [ABSTRACT FROM AUTHOR]

Background Neuroinfections in children are a socially significant problem of our time, as they can lead to disability and death of the patient, which actualizes the need for their early clinical diagnosis. The purpose of the study: to identify patterns of clinical manifestations of central nervous system lesions in children with neuroinfections. Materials and methods The cases of neuroinfections in 101 children treated at the "City Clinical Infectious Diseases Hospital" (Shymkent) in the period from 2018 to 2022 were analyzed, of which 37 patients with viral neuroinfections, 64 with bacterial ones. Results The predominance of bacterial neuroinfections over viral ones was revealed, with a predominance among young boys. Headache or its equivalents (in children under one year old) were observed in 72.5%; most often in children with viral infections of the nervous system (81.2%), less often in patients with bacterial infections (65.4%), p 0.01. In most cases, the disease manifested with the phenomena of fever and vomiting. When assessing the neurological status, the duration of preservation of two frequently occurring meningeal signs (rigidity of the occipital muscles, Kernig's symptom) was taken into account, which was 6 ± 1.3 days and 5 ± 1.1 days in the group with bacterial neuroinfections, and 4 ± 1.8 and 5 ± 1.7 days, respectively, in the group with viral neuroinfections (p 0.05). With pneumococcal etiology, the most severe and protracted cases of the course of neuroinfections are recorded. Frequent emergency conditions in infectious lesions of the central nervous system in the form of cerebral edema, septic shock, which occur more often in bacterial neuroinfections, have been identified. Conclusion Neuroinfections are characterized by a symptom complex of clinical manifestations, which should be interpreted by doctors in a timely and correct manner in order to diagnose early and minimize adverse outcomes of the disease. [ABSTRACT FROM AUTHOR]

Nocardia farcinica is the most pathogenic Nocardia, which is easy to disseminate. It can be caused by trauma, and even lead to severe lung or central nervous system infection. This report covers a case of Nocardia brain abscess in an HIV patient, who underwent resection of the brain abscess, followed by anti-infective therapy with sulfamethoxazole and meropenem, and eventually made a good recovery. The mortality rate of Nocardia farcinica brain abscess has been attributed to the severity of the underlying disease, the difficulty in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of treatment. Medication should follow the principle of sufficient dosage and sufficient course of treatment. [ABSTRACT FROM AUTHOR]

Background and Aims: Idiopathic intracranial hypertension (IIH) is a rare neurological disorder in the pediatric population which is defined as an increase in intracranial pressure (ICP) without the presence of brain parenchymal lesions, hydrocephalus, or central nervous system infection. In this study, we have determined the magnetic resonance imaging (MRI) findings in IIH patients. Methods: A comprehensive literature search was conducted using the electronic databases including Web of Sciences, Scopus, and Pubmed to identify suitable and relevant articles using keyword search methods. The search included keywords such as "idiopathic intracranial hypertension," "pseudotumor cerebri," "MRI," and "pediatrics." The search was limited to the available publications up to January 2024. Results: MRI plays a crucial role in diagnosing IIH by excluding secondary causes and revealing neuroimaging findings associated with elevated ICP. Despite fewer studies in children compared to adults, MRI serves as a cornerstone in identifying traditional neuroradiological markers such as empty sella turcica, posterior globe flattening, optic nerve tortuosity, optic nerve sheath distension, and transverse venous sinus stenosis. Additional subtle markers include increased Meckel's cave length, cerebellar tonsillar herniation, and slit‐like ventricles, although these are less reliable. Diffusion‐weighted imaging does not typically show cerebral ADC value changes indicative of cerebral edema in pediatric IIH. Conclusion: MRI findings provide valuable non‐invasive diagnostic indicators that facilitate early detection, clinical management, and potential surgical intervention in pediatric IIH. The reliability of these MRI markers underscores their importance in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. Results: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57–73% response rate). Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease in humans, characterized by tense blisters, erosions, urticarial lesions, and itching on normal or erythematous skin. Many autoimmune diseases are considered comorbidities of BP, but clinical case reports of BP complicated by Sjögren's syndrome are very scarce. Furthermore, cases of central nervous system infection secondary to both autoimmune diseases are even rarer. Case presentation: We report a 74-year-old woman diagnosed with bullous pemphigoid, who showed relief of active lesions after treatment with methylprednisolone and dupilumab injections. However, she was admitted for pulmonary infection during which she was diagnosed with Sjögren's syndrome (SS). Subsequently, the patient developed altered consciousness, indicating a central nervous system infection. Adjustment of steroid dosage and aggressive antimicrobial therapy led to alleviation of symptoms. Conclusion: The coexistence of autoimmune subepidermal blistering diseases and SS is rare. The role of SS in the pathogenesis of skin lesions is unclear, and the relationship between these blistering diseases and SS remains elusive. Further research is needed to determine whether there are common pathological mechanisms between the two conditions. [ABSTRACT FROM AUTHOR]

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22–71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Nocardia farcinica is an opportunistic bacterium that causes bovine mastitis and pulmonary, cutaneous, and central nervous system infections in humans. Bovine abortion caused by N. farcinica has been sporadically reported. The purpose of this study was to analyze the pathological findings of bovine abortions caused by N. farcinica in the Republic of Korea and determine the antimicrobial resistance and genotypical characteristics of N. farcinica isolates. Case presentation: Three cases of bovine abortions were submitted to the Animal and Plant Quarantine Agency for differential diagnosis. Grossly, one fetus showed severe lung consolidation following palpation of the entire lobes. Histologically, necrotizing granulomatous interstitial pneumonia was observed in all fetuses; a fetus with a gross lesion demonstrated necrotizing lymphadenitis in the mesenteric lymph nodes and necrotizing dermatitis in the ear. N. farcinica isolates were isolated from the abomasal contents and lungs of all fetuses. Finally, two cases were diagnosed as abortions due to N. farcinica, and one was diagnosed as an N. farcinica abortion coinfected with bovine viral diarrhea virus. According to the multilocus sequence analysis, all isolates were identified as N. farcinica and were determined to be genetically related to isolates from humans. Two N. farcinica isolates were resistant to trimethoprimsulfamethoxazole, which is recommended as the first treatment for human nocardial infections. Conclusion: This is the first pathological report of bovine abortion caused by N. farcinica in the Republic of Korea. Further studies are needed to phenotypically and genotypically characterize N. farcinica isolates with various sources and continuously monitor antimicrobial resistance patterns. [ABSTRACT FROM AUTHOR]

Introduction Central nervous system (CNS) infection due to the varicella zoster virus (VZV) can complicate the primary infection or the reactivation, leading to significant mortality and morbidity. This study aimed to describe the clinical, laboratory, and radiological characteristics of patients with confirmed VZV CNS infection in a tertiary hospital in Greece. Methods Data about patients hospitalized from January 2018 to September 2023 with CNS infection by VZV, confirmed by a syndromic polymerase chain reaction in the cerebrospinal fluid (CSF), were retrospectively collected and evaluated. Results In total, 14 patients were recorded. The median age was 49 years, and 35.7% were male. Headache was present in 71.4%, a rash in 57.1%, and fevers, nausea or vomiting, and disorientation in 35.7%. The CSF showed lymphocytic pleocytosis in all patients. Brain magnetic resonance imaging was performed in 53.8%. Empirical antivirals were given in 69.2%, and intravenous acyclovir was given to all patients after identification of VZV in the CSF. Only 7.1% (1 patient) required intensive care unit admission, and 7.1% (1 patient) died. Patients presenting without a rash may be slightly younger, have a slightly lower Charlson comorbidity index, be more likely to present with photophobia or phonophobia, and have lower serum CRP. Conclusions Patients presenting with VZV CNS infection have lymphocytic pleocytosis in the CSF and usually have a favorable outcome with antiviral treatment. Those presenting without a rash may have a different overall clinical phenotype from those with a rash; however, this must be evaluated in larger studies in the future. [ABSTRACT FROM AUTHOR]

Introduction Central nervous system infections pose significant health challenges, particularly in low- and middle-income countries, because of high morbidity and mortality rates. Rapid and accurate diagnosis is essential for effective treatment to prevent adverse outcomes. Traditional culture-based diagnostics are often slow and lack specificity. This study evaluates the BioFire FilmArray Meningitis/Encephalitis (FAME) Panel against standard diagnostics in Vietnam to assess its clinical impact and suitability for local epidemiology. Methods We conducted a prospective study involving 330 patients with suspected central nervous system infections at 4 hospitals in northern Vietnam from July 2022 to April 2023. Cerebrospinal fluid samples were analyzed using routine culture methods and FAME. We compared pathogen detection rates and assessed the potential clinical impact of FAME results on patient management. Results Of the 330 cerebrospinal fluid specimens, 64 (19%) were positive by either conventional diagnostics (n = 48) and/or FAME (n = 33). The agreement between FAME and conventional diagnostics was 87%. Key pathogens Mycobacterium tuberculosis (n = 7), Klebsiella pneumoniae (n = 5), Streptococcus suis (n = 5), Epstein-Barr virus (n = 3), Acinetobacter baumannii (n = 1), and Trichosporon asahii (n = 1) were not detected by FAME. Classical meningitis parameter clinical symptoms, altered glucose, protein, and pleocytosis were good predictors of FAME positivity, indicating their utility in optimizing local diagnostic algorithms. Conclusions FAME complements traditional diagnostics by offering rapid and broad pathogen detection, crucial for timely and appropriate therapy. However, its effectiveness varies with local epidemiology, and it should not replace conventional methods entirely. Tailoring diagnostic panels to regional pathogen prevalence is recommended to enhance diagnostic accuracy and clinical outcomes in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Soil is an environment for huge diversity of fungi, which fulfill various tasks and support the maintaining of soil health. At the same time, varieties of soil fungal species, which produce numerous airborne spores and a range of mycotoxins, are known to be pathogenic for human health. The present review aims to summarize the current knowledge on soil fungi causing public health problems, including dermatoses, allergies, pulmonary diseases, wound infections, infections of the central nervous system, etc. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central nervous system (CNS) in the period between May 2021 and December 2023 were included, with 85 TBE cases identified. The VirClia IgM assay was positive in the initial serum sample in 75/85 cases, giving a sensitivity of 88.2% (95% CI, 79.4–94.2). The ReaScan TBE IgM rapid test was positive in 80/85 cases, with an estimated sensitivity of 94.1% (95% CI, 86.8–98.1). Vaccine breakthrough infections were the predominant cause of non-reactive IgM cases. The calculated specificity for the VirClia IgM was 95.8% (95% CI, 92.5–98.0). In conclusion, the sensitivity of the VirClia IgM was non-inferior to the ReaScan TBE IgM rapid test. However, isolated IgM reactive results must be interpreted with caution, since false-reactive results occur. [ABSTRACT FROM AUTHOR]

Key Clinical Message: N meningiditis remains an important cause of central nervous system infection. A high index of suspicion is required especially in infants. While empirical antibiotics may be initiated, diagnostic measures must be adopted for guided therapy. Notification of such cases contributes to surveillance data and deciding on providing vaccines to the population. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) presents a formidable challenge to public health and clinical medicine. This dual phenotype of hypervirulence and multi-drug resistance often complicates treatment options, leaving patients with limited antimicrobial regimens. Consequently, adverse clinical outcomes and high mortality rates are common. Ceftazidime-avibactam (CAZ-AVI) is recognized globally as a critical option for treating infections caused by resistant gram-negative bacteria. Case Report: We present a case of invasive Klebsiella pneumoniae liver abscess syndrome caused by a CR-hvKP infection. The patient exhibited a bloodstream infection, lung and liver abscesses, and suppurative meningitis, eventually developing a brain abscess. Treatment with a combination of meropenem and CAZ-AVI led to a favorable clinical outcome. Conclusion: This case report indicates that combining CAZ-AVI with an antimicrobial agent that is in vitro non-susceptible (carbapenems in this case) is safe and effective for treating severe, multi-site infections caused by CR-hvKP, including central nervous system infections. This case serves as a clinical reference for managing similar patients in practice. [ABSTRACT FROM AUTHOR]

Zhen Zhang,1 Lei Tian2 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Lei Tian, Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Email iso15189@126.comPurpose: The optimal strategy for detecting central nervous system infections (CNSI) in cerebrospinal fluid (CSF) samples remains unclear.Methods: In a one-year, multicenter retrospective study, we examined the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional pathogen diagnostic techniques for CSF in diagnosing CNSI. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index for each diagnostic approach. Additionally, receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was determined to assess the diagnostic performance of each method.Results: The study included 68 patients, comprising both adults and children, who were suspected of having CNSI. Through the application of comprehensive clinical interpretation (CCI), the sensitivity and specificity of mNGS were found to be 67.6% (95% confidence interval [CI]: 50.85– 80.87%) and 45.8% (95% CI: 27.89– 64.92%), respectively. In comparison, traditional pathogenic diagnostic methods indicated that the culture method demonstrated a sensitivity of 10.6% (95% CI: 4.63– 22.6%) and a specificity of 100% (95% CI: 84.54– 100%). Furthermore, the sensitivity and specificity of the peripheral blood nucleated cell count were determined to be 34.0% (95% confidence interval: 22.17– 48.33%) and 57.1% (95% confidence interval: 36.54– 75.53%), respectively. CSF nucleated cell count demonstrated a sensitivity of 66.0% (95% confidence interval [CI]: 51.67– 77.83%) and a specificity of 61.9% (95% CI: 40.87– 79.25%). In comparison, the CSF protein content exhibited a sensitivity of 63.8% (95% CI: 49.54– 76.03%) and a specificity of 57.1% (95% CI: 36.54– 75.53%). When combining mNGS with traditional methodologies, the overall sensitivity increased to 91.3% (95% CI: 79.67– 96.56%), although the specificity was reduced to 18.2% (95% CI: 7.31– 38.51%). The area under the ROC curve for culture, peripheral blood nucleated cell count, mNGS, CSF nucleated cell count, and CSF protein content were 0.8088, 0.6038, 0.6103, 0.5588, and 0.5588, respectively. The variation in CSF nucleated cell count did not significantly affect the diagnostic efficacy of mNGS.Conclusion: Currently, both mNGS and traditional diagnostic methods encounter substantial challenges in diagnosing CNSI.Keywords: mNGS, CSF, central nervous system infections, ROC

Abstract Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities.

Background: Tuberculous meningitis (TBM) is a challenging condition to diagnose, and current laboratory methods have limitations, especially in developing countries. This study evaluated the diagnostic utility of the Lancet consensus scoring (LCS) system in suspected TBM cases at a tertiary care center in India. Methods: The clinical manifestations of 75 patients with suspected TBM were prospectively evaluated using the LCS system, which categorizes cases as “definite” (laboratory confirmed), “probable” (>10 points without imaging or > 12 points with imaging), and “possible” (6–9 points without imaging or 6–11 points with imaging). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the LCS system were compared to GeneXpert and mycobacterial growth indicator tube (MGIT) liquid culture, which are considered the gold standard tests. Results: Out of 75 recruited cases, 11 were confirmed as definite TBM cases. The LCS system correctly identified 8 of these as “probable” and 3 as “possible” cases. Compared to GeneXpert, the LCS system had a specificity of 100%, sensitivity of 54.55%, NPV of 92.7%, and PPV of 100%. Compared to MGIT liquid culture, the LCS system had a specificity of 100%, sensitivity of 81.82%, NPV of 96.97%, and PPV of 100%. The diagnostic accuracy was higher for MGIT liquid culture (97.33%) than GeneXpert (93.33%). Conclusion: The LCS system is a practical and easily applicable tool that can aid the diagnosis of suspected TBM cases, particularly in resource-limited settings. Despite some limitations, the LCS system demonstrated good diagnostic performance, suggesting its potential utility in improving TBM diagnosis and management.

Liying Zhan,1,&ast; Zhihua Lv,2,&ast; Yunjing Zhang,3,&ast; Jingdi Chen,4 Lu Wang,1 Raojuan Huang,5 Yaqi Sun,5 Wei Wu1 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Institute of Translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Orthopedics, the Airborne Military Hospital, Wuhan, Hubei, People’s Republic of China; 5First Clinical College of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, Email weiwu2012@whu.edu.cnPurpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.Methods: 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.Results: 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).Conclusion: 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.Keywords: metagenomic next-generation sequencing, cerebrospinal fluid, central nervous system infections, diagnosis

Abstract Introduction Anesthesiologists play an important role in the management of labor and delivery during acute malaria infection. The peripartum anesthesia considerations for such cases remain unclear. Findings Important peripartum considerations include the severity of thrombocytopenia and coagulopathy, hemodynamic status and cardiac disease, and the likelihood of central nervous system (CNS) involvement. Several antimalarial drugs may interact with perioperative medications, causing hypoglycemia, methemoglobinemia, or QT prolongation. Labor should usually not be induced. Patient volume status should be optimized pre-induction, but fluids should be administered with caution given the risk of cerebral edema. In case of CNS involvement intracranial pressure should be maintained. Case reports describe the successful use of neuraxial anesthesia but this approach requires further confirmation of safety. Despite the risks accompanying airway management in pregnancy, in some cases, general anesthesia was preferred due to the chance of CNS infection and disease complications. Tight postoperative assessments of neurological and bleeding status are indicated regardless of the mode of delivery. Conclusions Despite the prevalence of malaria, the perioperative risk and preferred mode of anesthesia for pregnant patients with acute malaria remain under-researched and outcome data are limited.

Objective To investigate the effect of cerebrospinal fluid (CSF) metagenomic next - generation sequencing (mNGS) in diagnosis and treatment of intracranial infection. Methods A retrospective analysis of 117 patients with intracranial infection were admitted to Shenzhen Second People's Hospital from January 2020 to December 2022. Before initiating empirical broad - spectrum antibiotic treatment, CSF samples were collected for microbial culture (conventional culture group, n = 58) and/or mNGS (mNGS group, n = 59). The results were used to adjust the antibiotic treatment plan, and the study compared the pathogen detection rates and result reporting times of the two testing methods, as well as the antibiotic intensity grading, the intensive care unit (ICU) stay, total hospital stay, and mortality rate. Results A total of 65 pathogens were detected from the CSF samples of all the patients through microbial culture and/or mNGS, with viruses being the most prevalent, accounting for 49.23% (32/65), followed by Gram-negative bacteria (24.62%, 16/65), Gram-positive bacteria (18.46%, 12/65) and fungi (7.69%, 5/65). The pathogen detection rate of CSF mNGS was higher than that of CSF microbial culture (χ2 = 22.781, P = 0.000), and the results were reported earlier (t = - 32.588, P = 0.000). Based on the results, 20 cases (33.90%) in the mNGS group adjusted antibiotic treatment plan, with 5 cases downgrading and 15 cases upgrading the intensity of antibiotic application. In the conventional culture group, 30 cases (51.72%) adjusted their antibiotic treatment plan, with 17 cases downgrading and 13 cases upgrading the intensity of antibiotic application. There was no significant difference between the 2 groups (Z = - 1.917, P = 0.055). And there was no statistically significant difference in ICU stay (Z = - 0.716, P = 0.474）, total hospital stay (Z = - 0.933, P = 0.351) and mortality rate (Fisher's exact probability: P = 0.496) between the 2 groups. Conclusions The application of mNGS can effectively improve the detection rate of intracranial infection pathogens, which may shorten the duration of antibiotic use and reduce the intensity of broad - spectrum antibiotics, so as to help clinical effective judgment and treatment decision.

Objective To investigate the efficacy of cluster therapy in the treatment of severe intracranial infection. Methods The clinical data of 43 patients with severe intracranial infection in Shenzhen University General Hospital and Shenzhen Second People's Hospital from July 2020 to June 2023 were retrospectively analyzed. Patients with intracranial infection were treated with cluster therapy: systemic broad-spectrum antibiotics were used at first; cerebrospinal fluid was obtained by multiple drainage routes for routine and biochemical testing, and then cultured and undertook next - generation sequencing (NGS); head/chest CT and brain MRI plain and enhanced scan were performed; after the NGS results were reported, precisely adjust the drug treatment according to the infection pathogen; sequentially use different drainage protocols of infected cerebrospinal fluid. Patients with severe intraventricular inflammation were treated with ventriculoscope (flexible endoscope) irrigation and fistula; cerebrospinal fluid, microbial culture and whole blood test for infection indicators were regularly extracted for laboratory test, and the type and dosage of antibiotics were adjusted one week after the indicators returned to normal, and the treatment effect of patients was judged comprehensively according to blood, cerebrospinal fluid, imaging results and clinical signs of infection. Results Sixteen patients were administered a broad - spectrum antibiotic regimen consisting of meropenem and vancomycin. Cerebrospinal fluid analysis revealed that 12 cases (27.91%) were culture-positive for microbial organisms (bacteria, fungi, viruses), while 35 cases (81.40%) yielded positive results in NGS. Upon identification of the pathogen via NGS, 15 cases were switched to targeted, sensitive antibiotics, with 12 cases exhibiting notable improvements in symptoms, and 3 cases demonstrating no significant changes. A total of 27 patients (62.79%) underwent surgical intervention, including 7 patients (16.28%) who underwent abscess puncture drainage, 6 patients (13.95%) who received Ommaya sac implantation, 11 patients (25.58%) who underwent external ventricular drainage (8 of whom also underwent ventriculoscopic irrigation and ventriculostomy), and 3 patients (6.98%) who were treated with lumbocisterna drainage. The length of hospitalization was 30 (19, 57) d. The 37 cases (86.05%) were successfully cured, while 6 cases (13.95%) died. Conclusions The cure rate of patients with severe intracranial infection was significantly improved after cluster therapy, and early initiation of cluster therapy can significantly improve the prognosis of patients, which is worthy of clinical application.

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder caused by a variety of factors, including age, genetic susceptibility, cardiovascular disease, traumatic brain injury, and environmental factors. The pathogenesis of AD is largely associated with the overproduction and accumulation of amyloid-β peptides and the hyperphosphorylation of tau protein in the brain. Recent studies have identified the presence of diverse pathogens, including viruses, bacteria, and parasites, in the tissues of AD patients, underscoring the critical role of central nervous system infections in inducing pathological changes associated with AD. Nevertheless, it remains unestablished about the specific mechanism by which infections lead to the occurrence of AD. As an important post-transcriptional RNA modification, RNA 5-methylcytosine (m5C) methylation regulates a wide range of biological processes, including RNA splicing, nuclear export, stability, and translation, therefore affecting cellular function. Moreover, it has been recently demonstrated that multiple pathogenic microbial infections are associated with the m5C methylation of the host. However, the role of m5C methylation in infectious AD is still uncertain. Therefore, this review discusses the mechanisms of pathogen-induced AD and summarizes research on the molecular mechanisms of m5C methylation in infectious AD, thereby providing new insight into exploring the mechanism underlying infectious AD. [ABSTRACT FROM AUTHOR]

This document explores the use of metagenomic next-generation sequencing (mNGS) as a diagnostic tool for infectious diseases. It highlights the limitations of traditional diagnostic methods and the potential of mNGS in identifying a wide range of pathogens. The document provides case studies that demonstrate the effectiveness of mNGS in diagnosing and treating infectious diseases. It also discusses the challenges of interpreting mNGS data and the need for standard protocols in its clinical use. Overall, the document emphasizes the potential of mNGS in improving patient outcomes and calls for ongoing innovation in the field. [Extracted from the article]

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and an immune response, which is associated with the development of neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). The activation of both innate and adaptive immune responses, involving microglia, macrophages, and T and B cells, while required for efficient viral control within the CNS, is also associated with neuropathology. Under pathological events, such as CNS viral infection, microglia/macrophage undergo a reactive response, leading to the infiltration of immune cells from the periphery into the brain, disrupting CNS homeostasis and contributing to the pathogenesis of disease. The Theiler's murine encephalomyelitis virus (TMEV)- induced demyelination disease (TMEV-IDD), which serves as a mouse model of MS. This murine model made significant contributions to our understanding of the pathophysiology of MS following subsequent to infection. Microglia/macrophages could be activated into two different states, classic activated state (M1 state) and alternative activated state (M2 state) during TMEV infection. M1 possesses the capacity to initiate inflammatory response and secretes pro-inflammatory cytokines, and M2-liked microglia/macrophages are antiinflammatory characterized by the secretion of anti-inflammatory cytokines. This review aims to discuss the roles of microglia/macrophages M1/M2-liked polarization during TMEV infection, and explore the potential therapeutic effect of balancing M1/M2-liked polarization of microglia/macrophages on MS. [ABSTRACT FROM AUTHOR]

Background: Febrile seizures are the most common type of childhood seizures occurring between 6months to 60 months of age in a febrile child without the evidence of infection of central nervous system, trauma or metabolic disturbances. They are benign conditions with good prognosis and around 1/3rd of the cases will have recurrences. There are certain risk factors contributing to the recurrence of febrile seizures. Objective: The aim of the present study was to find the risk factors associated with recurrence of febrile convulsions. Methods: This prospective observational study was done on 121 children from December 2018 to October 2019, admitted to Karnataka institute of medical sciences, Hubballi with febrile seizures and were followed up over 1 year period. Of these 32 children were diagnosed to have recurrence of febrile seizures. History regarding the risk factors was taken in each case along with examination and necessary investigations and data was analysed using mean + standard deviation (x + sd), chi square test and regression analysis and SPSS 21 Results: Among 121 children, 32 children (26.4%) had experienced recurrent febrile seizure. Mean age of recurrent febrile convulsion was 17 +/- 2.8 months. 31.2% of the children had their first episode of febrile seizure before 1 year of life. Male children (78.1%) are more commonly affected with recurrence. 31.2% of the children with recurrence had significant family history of febrile seizure as compared to 10.1% in those without recurrence. Conclusions: These findings revealed that age less than 1 year, male gender, duration of fever less than 1 hour prior to seizure, family history of febrile seizure, complex febrile seizures, prolonged seizure duration ( > 15 minutes), are risk factors for recurrence of febrile seizure. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of meningitis caused by Moraxella osloensis, a bacterium that is difficult to identify due to its similarities to other species. The patient initially presented with symptoms of headache, fever, and cranial nerve injury, leading to a diagnosis of viral meningitis. However, antiviral therapy did not improve the patient's condition, and conventional diagnostic methods were inconclusive. The use of metagenomic next-generation sequencing (mNGS) allowed for the accurate identification of the pathogen and guided appropriate antibiotic treatment. The patient ultimately recovered. The article emphasizes the importance of mNGS in cases where traditional diagnostic methods are ineffective and highlights the need for further research on susceptible groups for M. osloensis infection. [Extracted from the article]

Background: Central Nervous System (CNS) infections caused by Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a major clinical challenge and are associated with high mortality rates. Polymyxin is used as a salvage treatment for CRKP CNS infection; however, heteroresistance to polymyxin may impact clinical outcomes. In this study, we report a rare case of polymyxin-resistant Klebsiella intracranial infection, which was successfully treated with intravenous and intraventricular antibiotic injections. Case Presentation: A 46-year-old woman with a 1-day history of post-traumatic disturbance of consciousness and cerebrospinal fluid (CSF) rhinorrhea was referred to our hospital. She underwent external ventricular drainage and decompressive craniectomy, and had a persistent fever. A CSF test confirmed intracranial infection. The minimum inhibitory concentration of polymyxin in this patient was 16 μg/mL. She was diagnosed with polymyxin-resistant pan drug-resistant (PDR) Klebsiella pneumoniae (PDR-Kp) intracranial infection. We successfully treated the infection using intravenous ceftazidime/avibactam (CAZ/AVI) and polymyxin B, combined with an intraventricular injection of polymyxin B according to the CSF microbiological culture results. Conclusion: CAZ/AVI combined with polymyxin B may be an effective salvage treatment for CNS infections caused by polymyxin-resistant PDR-KP. [ABSTRACT FROM AUTHOR]

Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p < 0.05 as statistically significant threshold. Of the 111 enrolled cases, 57.7% (64/111) were diagnosed with central nervous system infections. From these cases, mNGS identified 39.6% (44/111) true-positive cases, 7.2% (8/111) false-positive case, 35.1% (39/111) true-negative cases, and 18.0% (20/111) false-negative cases. The sensitivity and specificity of mNGS were 68.7% (44/64) and 82.9% (39/47), respectively. Compared with culture, mNGS provided a higher pathogen detection rate in CNSIs patients (68.7% (44/64) vs. 26.5% (17/64), p < 0.0001). Compared to conventional methods, positive percent agreement and negative percent agreement was 84.60% (44/52) and 66.1% (39/59) separately. At a species-specific read number (SSRN) ≥ 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] 0.758, 95% confidence interval [CI] 0.663–0.854). In bacterial CNSIs patients with significant CSF abnormalities (CSF WBC > 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p < 0.0001). [ABSTRACT FROM AUTHOR]

Introduction: Anesthesiologists play an important role in the management of labor and delivery during acute malaria infection. The peripartum anesthesia considerations for such cases remain unclear. Findings: Important peripartum considerations include the severity of thrombocytopenia and coagulopathy, hemodynamic status and cardiac disease, and the likelihood of central nervous system (CNS) involvement. Several antimalarial drugs may interact with perioperative medications, causing hypoglycemia, methemoglobinemia, or QT prolongation. Labor should usually not be induced. Patient volume status should be optimized pre-induction, but fluids should be administered with caution given the risk of cerebral edema. In case of CNS involvement intracranial pressure should be maintained. Case reports describe the successful use of neuraxial anesthesia but this approach requires further confirmation of safety. Despite the risks accompanying airway management in pregnancy, in some cases, general anesthesia was preferred due to the chance of CNS infection and disease complications. Tight postoperative assessments of neurological and bleeding status are indicated regardless of the mode of delivery. Conclusions: Despite the prevalence of malaria, the perioperative risk and preferred mode of anesthesia for pregnant patients with acute malaria remain under-researched and outcome data are limited. [ABSTRACT FROM AUTHOR]