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

Mycoplasma pneumoniae, a frequent respiratory pathogen, can cause neurological disease manifestations. We here present a case of M. pneumoniae as cause of meningitis and occurrence of an intracranial abscess as a complication of mastoiditis with septic cerebral venous sinus thrombosis in a patient with multiple sclerosis on anti-CD20 therapy., (© 2024. The Author(s).)

Mixta calida , previously known as Pantoea calida , was initially isolated from powdered infant milk in 2010. It falls within the Erwiniaceae family (class: Enterobacterales). While Mixta calida was traditionally regarded as non-pathogenic, we now present a case of Mixta calida bacteraemia and meningitis in a 5-week-old child, successfully treated with cefotaxime. This case, in contrast to prior reports with potential contamination issues, is the first to offer compelling evidence of Mixta calida' s pathogenicity in humans.

Background: Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis., Methods: This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria., Results: Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis., Conclusion: In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Rationale: Meningitis caused by concurrent infections with Cryptococcus neoformans, Streptococcus equi subsp. equi, and Mycobacterium tuberculosis is extremely rare., Patient Concerns: We present the case of a 63-year-old male patient who presented with headaches, dizziness, nausea, vomiting, and fever for the past 3 weeks., Diagnoses: The patient was diagnosed with concurrent cryptococcal, streptococcal, and tuberculous meningitis., Interventions: The patient received isoniazid, rifampicin, ethambutol, and levofloxacin for 1 month, in addition to liposomal amphotericin B with flucytosine for 2 weeks, followed by fluconazole with flucytosine for additional 2 weeks., Outcomes: The symptoms improved, and outpatient therapy was continued., Lessons: Infectious meningitis requires a combination of microscopy, culture, and rapid molecular diagnostics for early diagnosis and treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We present the case of a young female health worker, resident in a high Andean region of Peru, with recent exposure to farm animals and arthropods, who developed acute febrile undifferentiated syndrome, severe thrombocytopenia and pulmonary and abdominal extravasation. Subsequently, the patient developed meningitis and early onset bilateral neurosensorial hypoacusis and showed reactive serology to acute infection by Rickettsia sp. Epidemiological and clinical considerations in the differential diagnosis for early management are discussed.

Introduction: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB., Clinical Findings: We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision., Diagnosis: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients., Conclusion: NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella., (© 2024. The Author(s).)

Background: Pantoea agglomerans (P. agglomerans) is a gram-negative bacterium that is commonly isolated from plant surfaces, seeds, and the environment. As an opportunistic pathogen, it can cause blood, urinary and soft tissue infections in immunocompromised patients. In central nervous system, P. agglomerans infection has been report in children and immune-compromised patients, however, infection by such bacterium in nontraumatized immune competent adults has not been reported. Here, we report a case of P. agglomerans cerebrospinal meningitis accompanied by positive anti-myeloperoxidase (MPO) antibody in a 49-year-old female who has a history of black fungus planting., Case Presentation: The patient manifested with repeated fever, headache, generalized muscle pain, and neurological defects. Cerebrospinal fluid (CSF) tests revealed a moderately elevated number of polymorphonuclear leukocytes (50-193 × 10 6 /L), low glucose levels (0.54-2.44 mmo1/L), and extremely high protein content (2.42-25.42 g/L). Blood tests showed positive anti-myeloperoxidase antibodies lasting for 1.5 year before turning negative. Spine MRI showed thickening and enhancement of the whole spinal meninges. CSF metagenomic next-generation sequencing (mNGS) revealed 75,189 specific DNA reads of P. agglomerans. The patient underwent spinal laminectomy due to meningeal adhesions. Pathological results revealed fibrous tissue proliferation, inflammatory infiltration with focal necrosis and calcification in the dura mater. The patient was successfully treated with sufficient antibiotics at 1-year follow-up., Conclusions: People should be alert to CNS infections caused by P. agglomerans which presented with relatively mild clinical symptoms at onset, especially for those who contucts relevant agricultural and forestry work. The CSF characterization of P. agglomerans meningitis is elevated multiple nuclei white blood cells, significantly reduced glucose content, and markedly increased protein level which may be related to the secondary spinal membrane adhesions., (© 2024. The Author(s).)

Subacute and chronic meningitis (SCM) presents significant diagnostic challenges, with numerous infectious and non-infectious inflammatory causes. This study examined patients aged 16 and older with SCM admitted to referral centers for neuroinfections and neuroinflammations in Mashhad, Iran, between March 2015 and October 2022. Among 183 episodes, tuberculous meningitis was the most common infectious cause (46.5%), followed by Brucella meningitis (24.6%). The cause of SCM was definitively proven in 40.4%, presumptive in 35.0%, and unknown in 24.6% of cases. In-hospital mortality was 14.4%, and 30.5% of survivors experienced unfavorable outcomes (Glasgow Outcome Scale 2-4). Patients with unknown causes had a significantly higher risk of death compared to those with presumptive or proven diagnoses (risk ratio 4.18). This study emphasizes the diagnostic difficulties of SCM, with one-quarter of cases remaining undiagnosed and over one-third having only a presumptive diagnosis. Improving diagnostic methods could potentially enhance prognosis and reduce mortality.

We present a case of Streptococcus iniae causing leptomeningitis, pyocephalus, and subdural empyema in an elderly male from India. There have been only a handful of cases of S. iniae infection reported worldwide, and none of them have been from India. In this case, an elderly diabetic patient presenting with backache, headache, and fever with severe neurological worsening was diagnosed with severe invasive S. iniae infection. He had hydrocephalus that needed ventriculoperitoneal shunting. The patient was treated with a prolonged course of intravenous ampicillin and vancomycin., (© Journal of the Association of Physicians of India 2024.)

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

Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Purpose: To evaluate the diagnosis and management of bacterial meningitis in adult Sudanese patients in accordance with the Infectious Diseases Society of America (IDSA) guidelines for bacterial meningitis management., Patients and Methods: A cross-sectional, retrospective study design was used to recruit all patients aged > 18 years who were diagnosed with or suspected of having bacterial meningitis and admitted to Wad Medani Teaching Hospital, Gezira State, Sudan, between January 2017 and October 2022., Results: In total, 201 patients were included in the analysis. The mean age of the participants was 44.1 ± 21.4 years, and 107 (53.2%) were male. Community-acquired bacterial meningitis accounted for 193 (96%) of the studied patients, and only 8 (4%) of the patients had healthcare-associated meningitis. Neuroimaging was utilized appropriately in 148 (73.6%) patients, blood cultures were not performed entirely, and lumbar puncture was seldom performed in 1 (0.5%) patient. Corticosteroids were appropriately administered to 65 (32.3%) patients, and antibiotics were administered appropriately to only 5 (2.5%) patients. Ceftriaxone 185 (76.1%) was the most frequently utilized antibiotic, followed by vancomycin 23 (9.5%). In terms of overall adherence, this study demonstrated that the IDSA guidelines were not followed at all in the treatment of patients with suspected bacterial meningitis., Conclusion: The results of this study contradict the IDSA guidelines for the standard of care for bacterial meningitis. Antibiotic regimens are often incorrect, corticosteroids are administered appropriately in approximately one-third of patients, and neuroimaging is reasonably utilized. This study raises attention to several important issues regarding the diagnosis of bacterial meningitis, including the lack of confirming microbiological tests and the reliance of the diagnosis primarily on CT and clinical examination., (© 2024. The Author(s).)

BACKGROUND Except for neonates, streptococci other than Streptococcus pneumoniae are a rare cause of acute bacterial meningitis. Streptococcus constellatus is a member of the Streptococcus anginosus group of gram-positive streptococci. It is a commensal microbe of the mucosae of the oral cavity, gastrointestinal tract, and urogenital tract. Rarely, it becomes pathogenic and causes contiguous or distant infections after mucosal damage. This report describes a 19-year-old immunocompetent man who developed bacterial meningitis, lung abscess, and brainstem infarct secondary to Streptococcus constellatus. CASE REPORT A 19-year-old immunocompetent man presented to the Emergency Department with a 4-week history of headache and neck pain. He was febrile on arrival. Physical examination revealed ataxia, upper-limb discoordination, and a positive Brudzinski sign. Cerebrospinal fluid and blood cultures were positive for Streptococcus constellatus, identified by matrix-assisted laser desorption ionization - time of flight mass spectrometry. Computed tomography of the chest demonstrated a lung abscess measuring 7×3.5×3 cm. A magnetic resonance imaging scan of the head revealed a 1.8×0.7 cm acute infarct in the right pons. The patient was treated initially with intravenous ceftriaxone and vancomycin before culture and sensitivity results, in addition to intravenous dexamethasone. After culture and sensitivities resulted, antibiotics were transitioned to a 4-week course of intravenous penicillin. The patient survived with no neurological consequences upon discharge. CONCLUSIONS Streptococcus constellatus should be suspected as an etiological agent for bacterial meningitis and other rare complications such as brainstem infarction and lung abscess, even in immunocompetent patients.

Objectives: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation., Methods: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection., Primary and Secondary Outcome Measures: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM., Results: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates., Conclusions: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing., Competing Interests: Competing interests: We do not have any association with commercial entities that provided support for the work reported in the submitted manuscript. We do not have any association with commercial entities that could be viewed as having an interest in the general area of the submitted manuscript. We do not have any association involving spouses or children under 18 years of age., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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

Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Updating the vaccination recommendations against meningococci and pneumococci, in particular the introduction of the B vaccine as the standard vaccination for infants from January 2024 and the adaptation of the pneumococcal vaccination strategy for infants and adults aged 60 and over with the latest conjugate vaccines (PCV13, PCV15, PCV20).Emphasis on the need for rapid diagnostic lumbar puncture and simultaneous serum and cerebrospinal fluid analysis to increase diagnostic precision. The introduction of procalcitonin (PCT) in serum as an additional biomarker to differentiate between bacterial and viral meningitis.The use of multiplex PCR as a supplement, not a replacement, for standard diagnostics to speed up pathogen identification.Adaptation of antibiotic recommendations based on the current resistance situation, in particular for meningococcal meningitis, consideration of penicillin G only after resistance testing.Clarification of the areas and duration of use of dexamethasone in bacterial meningitis, particularly in pneumococcal meningitis and the controversial data situation in Listeria meningitis.New findings on the safe use of heparin in septic sinus thrombosis without increased risk of hemorrhage., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days., Methods: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.4 F who underwent an ED evaluation with blood and urine cultures. Models to predict IBI were developed and validated respectively using a random 80/20 dataset split, including 10-fold cross-validation. We used precision recall curves as the classification metric., Results: Of 4411 eligible infants with a mean age of 37 days, 29% had characteristics that would likely have excluded them from existing risk stratification protocols. There were 196 patients with IBI (4.4%), including 43 (1.0%) with bacterial meningitis. Analytic approaches varied in performance characteristics (precision recall range 0.04-0.29, area under the curve range 0.5-0.84), with the XGBoost model demonstrating the best performance (0.29, 0.84). The five most important variables were serum white blood count, maximum temperature, absolute neutrophil count, absolute band count, and age in days., Conclusion: A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms., Impact: Several models for the risk stratification of febrile infants have been developed. There is a need for a preferred comprehensive model free from limitations and algorithm exclusions that accurately predicts IBIs. This is the first study to derive an all-inclusive predictive model for febrile infants aged 7-60 days in a community ED sample with IBI as a primary outcome. This machine learning model demonstrates potential for clinical utility in predicting IBI., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Meningitis caused by Moraxella osloensis is rare and easily misdiagnosed clinically. Here, we report the first case of meningitis caused by M. osloensis in China by taking advantage of the metagenomic next-generation sequencing technology in cerebrospinal fluid for pathogen screening. In addition, we extend the neurological signs, clinical symptoms, diagnostic methods, and treatment of this rare disease., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Sensorineural hearing loss is a well-known complication of Streptococcus pneumoniae meningitis. Given the propensity for fibrosis and ossification of the cochlea in bacterial meningitis, implantation must be performed in a timely fashion because a delayed attempt at implantation can frustrate obtaining an optimal technical result or lead to an inability to implant. Obtaining optimal audiometric outcomes is reliant on early hearing screening in patients with streptococcal meningitis. In the absence of standardized protocols, audiometric testing is often overlooked or delayed in the workup and management of meningitis. Our institution implemented a meningitis protocol with a particular focus on timing of audiometric testing in patients with meningitis. We present a patient diagnosed with streptococcal meningitis in the first week of life. Early hearing screening allowed the diagnosis of profound unilateral sensorineural hearing loss and subsequent cochlear implantation at 10 weeks of age, the youngest described in the medical literature. Despite early implantation, there was cochlear fibrosis at the time of implantation. Fortunately, the majority of electrodes were implanted to achieve a serviceable hearing outcome. Serial magnetic resonance imaging scans were obtained because of her contralateral ventriculoperitoneal shunt that allowed unique visualization of the progression of cochlear fibrosis over time. This case demonstrates the importance of including audiometric testing in a standardized meningitis protocol to diagnose hearing loss in a timely and accurate way and to achieve optimal long-term hearing outcomes., (Copyright © 2024 by the American Academy of Pediatrics.)

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

Purpose: Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes., Methods: We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands. Both studies included patients ≥ 16 years, suspected of a central nervous system (CNS) infection, who underwent a diagnostic lumbar puncture. All episodes with elevated CSF leukocytes (≥ 5 cells per mm 3 ) were selected and categorized by clinical diagnosis (reference standard)., Results: Of 1261 episodes, 625 (50%) had elevated CSF leukocytes and 541 (87%) were included. 117 of 541 (22%) were diagnosed with bacterial meningitis, 144 (27%) with viral meningoencephalitis, 49 (9%) with other CNS infections, 76 (14%) with CNS autoimmune disorders, 93 (17%) with other neurological diseases and 62 (11%) with systemic diseases. The area under the curve to discriminate bacterial meningitis from other diagnoses was 0.97 (95% confidence interval [CI] 0.95-0.98) for CSF granulocyte count and 0.93 (95% CI 0.91-0.96) for CSF granulocyte percentage. CSF granulocyte predominance occurred in all diagnostic categories. A cutoff at 50% CSF granulocytes gave a sensitivity of 94% (95% CI 90-98), specificity of 80% (95% CI 76-84), negative predictive value of 98% (95% CI 97-99) and positive predictive value of 57% (95% CI 52-62)., Conclusion: CSF granulocytes have a high diagnostic accuracy for bacterial meningitis in patients suspected of a CNS infection. CSF granulocyte predominance occurred in all diagnostic categories, limiting its value in clinical practice., (© 2024. The Author(s).)

Introduction: This study aimed to determine the diagnostic value of interleukin (IL)-6, IL-8, IL-17, tumour necrosis factor-alpha (TNF-α) and D-lactate levels in the cerebrospinal fluid (CSF) of nosocomial meningitis patients., Methods: The CSF levels of cytokines and D-lactate were compared across 29 episodes of nosocomial meningitis, 38 episodes of pleocytosis (without meningitis) and 54 control subjects., Results: The CSF levels of IL-6, IL-8, and D-lactate were higher in the group with nosocomial meningitis compared to the control group and the group with pleocytosis without meningitis ( P < 0.05). For IL-6 levels (threshold: >440 pg/mL), the sensitivity and specificity were 55.17% and 94.74%, respectively. For IL-8 levels (threshold: >1,249 pg/mL), the sensitivity and specificity were 44.83% and 84.21%, respectively. In patients with nosocomial meningitis, when the threshold of D-lactate levels was >1.05 μmol/mL, the sensitivity and specificity were 75.86% and 63.16%, respectively. In pleocytosis (without meningitis) CSF samples and in nosocomial meningitis CSF samples, the highest area under the receiver operating characteristic curve (AUC) was calculated for triple combination model of IL-6, IL-8 and D-lactate levels (AUC 0.801, P < 0.001) and double combination model of IL-6 and IL-8 (AUC 0.790, P < 0.001)., Conclusion: Our study findings suggest that IL-6, IL-8 and D-lactate levels could be diagnostic markers for nosocomial meningitis., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

The rapid and accurate diagnosis of meningitis is critical for preventing severe complications and fatalities. This study addresses the need for accessible diagnostics in the absence of specialized equipment by developing a novel diagnostic assay. The assay utilizes dual-priming isothermal amplification (DAMP) with unique internal primers to significantly reduce non-specificity. For fluorescence detection, the dye was selected among Brilliant Green, Thioflavin T, and dsGreen. Brilliant Green is preferred for this assay due to its availability, high fluorescence level, and optimal sample-to-background (S/B) ratio. The assay was developed for the detection of the primary causative agents of meningitis ( Haemophilus influenzae , Neisseria meningitidis , and Streptococcus pneumoniae ), and tested on clinical samples. The developed method demonstrated high specificity, no false positives, sensitivity comparable to that of loop-mediated isothermal amplification (LAMP), and a high S/B ratio. This versatile assay can be utilized as a standalone test or an integrated assay into point-of-care systems for rapid and reliable pathogen detection.

A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.

Background: Meningitis can be caused by a variety of pathogenic microorganisms, which can lead to higher mortality and disability rates. However, the clinical manifestations of suppurative meningitis are often atypical in infants and young children, which makes early clinical diagnosis difficult.PAR and LAR are considered as a novel inflammatory biomarker and have been applied in tumors, IgA nephropathy, sepsis., Objective: To investigate the application of platelet/albumin (PAR) and lactate dehydrogenase/albumin (LAR) in refractory suppurative meningitis in infants., Methods: The relevant clinical data of 107 children with suppurative meningitis were retrospectively analyzed, and were divided into common group (82 cases) and refractory group (25 cases) according to the severity of the disease according to the relevant clinical consensus. The relevant clinical data and laboratory examination of the children in the two groups were compared. The diagnostic value of PAR and LAR in children with refractory suppurative meningitis was analyzed and multivariate Logistic regression analysis was performed., Result: The PAR of children with suppurative meningitis in refractory group was lower than that in common group (P < 0.05), while LAR was higher than that in common group (P < 0.05). Meanwhile, multivariate Logistic regression analysis showed that LAR and cerebrospinal fluid glucose ≤ 1.5mmo/L were risk factors for poor prognosis (OR > 1, P < 0.05). PAR was a protective factor (OR < 1, P < 0.05)., Conclusion: PAR and LAR can be used for early diagnosis of refractory suppurative meningitis in children as protective and risk factors, respectively., (© 2024. The Author(s).)

Acute pyogenic meningitis is a medical emergency. Bacteria are the major causative agents of pyogenic meningitis with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis being the most common. Here, we describe a case of bacterial meningoencephalitis caused by Streptococcus porcinus. To our knowledge this is the first case described in literature. The patient was treated with ceftriaxone and supportive treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Bacterial meningitis is an acute infection which requires rapid diagnosis and treatment due to the high mortality and serious consequences of the disease. The purpose of this study was to design a homemade multiplex PCR and a novel fluorescence biosensor on chip (FBC) to detect three important agents of meningitis including Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and Haemophilus influenzae (H. influenzae). The homemade multiplex PCR can diagnose three bacterial species simultaneously. Fabrication of FBC was carried out based on the deposition of lead nanoparticles on a quartz slide using the thermal evaporation method. Then, the SH-Cap Probe/Target ssDNA /FAM-Rep probe was loaded on lead film. The evaluation of the fluorescence reaction when the probes bind to the target ssDNA was assessed by a Cytation 5 Cell Imaging Multimode Reader Bio-Tek. The limit of detections (LOD) in homemade PCR and FBC to identify S. pneumoniae were 119 × 10 2  CFU/mL (0.27 ng/μL) and 380 CFU/mL (9 pg/μL), respectively. The LODs of homemade PCR and FBC for detection of N. meningitidis were 4.49 CFU/mL (1.1 pg/μL) and 13 × 10 3  CFU/mL (30 pg/μL), respectively. Our results confirmed the LODs of homemade PCR and FBC in detection of H. influenzae were 15.1 CFU/mL (30 fg/μL) and 41 × 10 2  CFU/mL (90 pg/ μL), respectively. Both techniques had appropriate sensitivity and specificity in detection of S. pneumoniae, N. meningitidis and H. influenzae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2-6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon., Patient Concerns: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation., Diagnoses: The patient was diagnosed with a central nervous system infection., Interventions: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders., Outcomes: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided., Conclusions: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective., Lession: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy., Methods: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL)., Results: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM., Conclusions: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM., (© 2024. The Author(s).)

Although the frequency of community-acquired infections caused by Klebsiella pneumoniae subsp. ozaenae (K. ozaenae) is low, they are often detected in sputum specimens. In addition, lung abscesses, necrotizing pneumonia, and urinary tract infections caused by K. ozaenae have also been reported. We herein report the first detection of K. ozaenae as an etiological agent of bacterial meningitis in Japan. Cases of K. ozaenae meningitis complicated by diabetes mellitus and sinusitis have been reported elsewhere. When Klebsiella pneumoniae is detected in such cases, it is important to use other detection methods in addition to mass spectrometry for correct identification.

Background: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations., Methods: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier)., Results: The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid., Conclusions: Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy., Competing Interests: Potential conflicts of interest . J. S. B. is supported by an NICHD grant (1 R01 HD095547-01). J. B. B. is supported by NIAID grants (R01 AI130185 and R01 AI136803). K. H., C. I., E. H., and P. Y. are career officers with the CDC. J. B. reports consulting fees from MicuRx Pharmaceuticals Inc, Aerovate Therapeutics, and Lupin and honorarium for a lecture under T32 (William Shafer, Emory) on antimicrobial pharmacology. A. W. K. reports stock from Pfizer, Johnson & Johnson, and AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

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

Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections., (© American Academy of Pediatrics, 2024. All rights reserved.)

Background and Objectives: Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies., Methods: This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA., Results: We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis., Conclusion: The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition., (© 2024. The Author(s).)

Introduction: Streptococcus suis is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with S. suis can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as Meningococcus , Streptococcus pneumoniae , and Haemophilus influenzae , S. suis infections in humans have been reported only rarely., Methods: This case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. S. suis was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was S. suis meningitis and sepsis., Results: The patient survived with hearing loss in both ears and dizziness at the 60-day follow-up., Discussion: We reported a case of S. suis infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human S. suis meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human S. suis meningitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Liu and Jia.)

A case of neonatal sepsis caused by Edwardsiella tarda , an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda , while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cerebrospinal fluid (CSF) white blood cell (WBC) count, protein, and glucose (cytochemistry) are performed to aid in the diagnosis of meningitis in young infants. However, studies have reported varying diagnostic accuracies. We assessed the diagnostic accuracy of CSF cytochemistry in infants below 90 days and determined the certainty of evidence., Study Design: We searched PubMed, Embase, Cochrane Library, Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases in August 2021. We included studies that evaluated the diagnostic accuracy of CSF cytochemistry compared with CSF culture, Gram stain, or polymerase chain reaction in neonates and young infants <90 days with suspected meningitis. We pooled data using the hierarchical summary receiver operator characteristic (ROC) model., Results: Of the 10,720 unique records, 16 studies were eligible for meta-analysis, with a cumulative sample size of 31,695 (15 studies) for WBC, 12,936 (11 studies) for protein, and 1,120 (4 studies) for glucose. The median (Q 1 , Q 3 ) specificities of WBC, protein, and glucose were 87 (82, 91), 89 (81, 94), and 91% (76, 99), respectively. The pooled sensitivities (95% confidence interval [CI]) at median specificity of WBC count, protein, and glucose were 90 (88, 92), 92 (89, 94), and 71% (54, 85), respectively. The area (95% CI) under ROC curves were 0.89 (0.87, 0.90), 0.87 (0.85, 0.88), and 0.81 (0.74, 0.88) for WBC, protein, and glucose, respectively. There was an unclear/high risk of bias and applicability concern in most studies. Overall certainty of the evidence was moderate. A bivariate model-based analysis to estimate the diagnostic accuracy at specific thresholds could not be conducted due to a paucity of data., Conclusion: CSF WBC and protein have good diagnostic accuracy for the diagnosis of meningitis in infants below 90 days of age. CSF glucose has good specificity but poor sensitivity. However, we could not identify enough studies to define an optimal threshold for the positivity of these tests., Key Points: · Median specificity of CSF leucocyte count, protein and glucose are similar in young infants.. · At median specificity, CSF leukocyte count and protein are more sensitive than glucose.. · Owing to inadequate data, bivariate modelling to suggest optimal diagnostic thresholds is not possible.., Competing Interests: None declared., (Thieme. All rights reserved.)

Streptococcus agalactiae is a rare cause of meningitis in healthy adults. We herein report a case of culture-negative Streptococcus agalactiae meningitis in a healthy adult which was diagnosed using the FilmArray Meningitis and Encephalitis Panel. A healthy 22-year-old man presented with a fever, headache, and neck stiffness. Despite negative results from blood and cerebrospinal fluid cultures, the diagnosis was confirmed using the FilmArray Meningitis and Encephalitis Panel. The patient was treated with dexamethasone, vancomycin, and ceftriaxone, and thereafter recovered completely. This report highlights the importance of being aware that Streptococcus agalactiae meningitis can occur in healthy individuals, and summarizes these features.