Frequency of Hyponatremia in Adults with Acute Bacterial Meningitis.

Bacterial meningitis is a life-threatening disease. Bacterial meningitis patients are prone to develop acute hyponatremia. In the central nervous system infection hyponatremia could be due to the Syndrome of Inappropriate Anti Diuretic Hormone secretion. The frequency of hyponatremia in adults with acute bacterial meningitis patients was seen in this study. This cross-sectional study was conducted in the Internal Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from February 2016 to July 2016. A total of 50 patients were enrolled in this study by purposive sampling. Among 50 acute bacterial meningitis patients, 33 (66%) were diagnosed as hyponatremic state. The mean serum sodium level of 33 hyponatremic bacterial meningitis cases was 130.66±2.95 mmol/L. Most of the cases (78.79%) were mild hyponatremic state (130 mmol/L-135 mmol/L) whereas 18.18% were revealed as moderate hyponatremia (125 mmol/L-129 mmol/L). Only 3.03% of cases were presented as severe cases (≤124 mmol/L). The result revealed that a large number of patients with acute bacterial meningitis were suffering from hyponatremia and in the majority of cases were mildly hyponatremic.

Streptococcus gallolyticus Subspecies (subsp.) pasteurianus Meningitis in a 7-week-old Boy.

Meningitis caused by Streptococcus gallolyticus subspecies (subsp.) pasteurianus is a rare complication with 14 cases reported in literature worldwide between 2003-2023, with the majority of the cases occurring before 4 weeks of life and with preceding symptoms. This is a case report of an infection without any preceding symptoms. A previously healthy 7-week-old boy presented to the hospital with a fever for 1 day. Blood and cerebrospinal fluid cultures ultimately grew Streptococcus gallolyticus subsp. pasteurianus. The magnetic resonance imaging was consistent with meningitis. The boy received 21 days of intravenous antibiotics before discharge. At subsequent visits, the boy had no neurological sequelae, normal hearing tests, and appeared to have met all developmental milestones. The older age of infant should not discount the differential diagnosis for meningitis, which may delay further work up such as a lumbar puncture. Group D streptococcus is an uncommon cause of infantile sepsis that can lead to several complications such as meningitis and bacteremia. In this case, the infant's subsequent post-meningitis clinical course has been unremarkable. The history of meningitis poses increased risk for abnormal neurodevelopmental outcome. This case study highlights the importance of keeping meningitis on the differential diagnosis for an infant with fever. If there is a concern for meningitis, further workup should be performed without delay.

Clinical characteristics and antimicrobial therapy of healthcare-associated carbapenem-non-susceptible gram-negative bacterial meningitis: a 16-year retrospective cohort study.

OBJECTIVE: Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. METHODS: This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. RESULTS: A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan-Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). CONCLUSIONS: Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients' outcome. TRIAL REGISTRATION: This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020).

Streptococcus suis meningitis: An emerging zoonotic disease in Brazil.

Streptococcus suis has been widely reported as a pathogen in animals, especially pigs. In terms of human health implications, it has been characterized as a zoonosis associated with the consumption of pork products and occupational exposure, particularly in Southeast Asian countries. Here, we present a rare case of human S. suis infection in Brazil, diagnosed in an older adult swine farmer, a small rural producer residing in the semi-arid region of Bahia, Brazil.

Shifts in Diagnostic Testing for Headache in the Emergency Department, 2015 to 2021.

Importance: Subarachnoid hemorrhage is typically diagnosed by noncontrast head computed tomography (CT); lumbar puncture is recommended if computed tomography is nondiagnostic, although CT cerebral angiography has been promoted as an alternative to lumbar puncture in this diagnostic pathway. The outcomes of this debate in practice have not been studied. Objective: To determine whether CT cerebral angiography use has increased in lieu of lumbar puncture among emergency department (ED) patients with headache, with an increase in unruptured intracranial aneurysm detection. Design, Setting, and Participants: This retrospective cohort study took place in 21 community EDs of an integrated health care system in Northern California between 2015 and 2021. Participants were adult (aged >17 years) health plan members with a chief concern of headache. Exclusions were prior diagnoses of subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral arteriovenous malformation, or cerebrospinal fluid shunt. Data were analyzed from October to November 2023. Exposures: CT cerebral angiography and/or lumbar puncture during the ED encounter. Main Outcomes and Measures: Primary and secondary outcomes were 14-day and 90-day unruptured intracranial aneurysm detection, respectively. Safety outcomes were missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. The annual incidence of unruptured intracranial aneurysm detection was normalized to the incidence of subarachnoid hemorrhage (UIA:SAH ratio). Average annualized percentage changes were quantified using joinpoint regression analysis. Results: Among 198 109 included ED encounters, the mean (SD) age was 47.5 (18.4) years; 140 001 patients (70.7%) were female; 29 035 (14.7%) were Black or African American, 59 896 (30.2%) were Hispanic or Latino, and 75 602 (38.2%) were White. Per year, CT cerebral angiography use increased (18.8%; 95% CI, 17.7% to 20.3%) and lumbar punctures decreased (-11.1%; 95% CI, -12.0% to -10.4%), with a corresponding increase in the 14-day UIA:SAH ratio (3.5%; 95% CI, 0.9% to 7.4%). Overall, computed tomography cerebral angiography use increased 6-fold relative to lumbar puncture, with a 33% increase in the detection of UIA. Results were similar at 90 days and robust to sensitivity analyses. Subarachnoid hemorrhage (1004 cases) and bacterial meningitis (118 cases) were misdiagnosed in 5% and 18% of cases, respectively, with no annual trends (P = .34; z1003 = .95 and P = .74; z117 = -.34, respectively). Conclusions and Relevance: In this cohort study of ED patients with headache, increases in CT cerebral angiography use were associated with fewer lumbar punctures and higher detection of unruptured intracranial aneurysms, with no significant change in missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. While this shift in diagnostic strategy appeared safe in the short-term, the long-term consequences remain unclear.

A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.

PURPOSE: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice. METHODS: We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function. RESULTS: Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis. CONCLUSIONS: Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is robust and can affect all three scalae. Our results suggest that CCR2 may assist in controlling infection and maintaining cochlear patency, as CCR2 knockout mice experienced more severe disease, more rapid hearing loss, and more advanced cochlear ossification after pneumococcal meningitis. CX3CR1 also may play an important role in the maintenance of cochlear patency.

Post Trauma Acinetobacter Baumanii Meningitis Treatment Approach.

A. baumannii, which is said to be associated with nosocomial infections is considered a significant mortality risk if not adequately addressed. A. baumannii infections typically occur in the aftermath of surgery or trauma. Our patient developed complicated A. baumannii meningitis with lateral ventriculitis and a lumbar abscess post surgery after suffering from a fall. The patient was treated with a 21-day regimen of intrathecally administered colistin and polymyxin B. Following this therapeutic period, the patient's condition improved, ultimately leading to successful recovery and subsequent discharge. This case report serves to highlight the ability of intrathecal administration of antibiotics, that normally have limited potential of crossing the blood-brain-barrier, to lead to improved survival outcomes in multi-drug resistant nosocomial meningitis.

Immunocompromised teenager with meningitis caused by Ureaplasma parvum.

Infection in the immunocompromised patient is often challenging on multiple levels. It can be difficult to distinguish between manifestations of the underlying disease, infection or malignancy. Symptoms may be vague or even absent, deviations in the common inflammatory parameters discrete, imaging findings scarce and the causative microbe may be a true pathogen as well as opportunistic. Here, we report an immunosuppressed female in her late teens with a purulent meningitis due to Ureaplasma parvum-a very rare cause of infection in the central nervous system of adults. We wish to highlight the relevance of intracellular pathogens and the need to actively search for these microbes, especially when response to broad-spectrum antibiotic treatment is absent. Furthermore, we emphasise the need for adequate molecular microbial diagnostics in search of microbes that are difficult to identify by culture and where serology and antigen tests may be absent or unreliable due to immune suppression.

Determine the factors affecting the time to recovery of children with bacterial meningitis at Jigjiga university referral hospital in the Somali Regional State of Ethiopia: using the parametric shared frailty and AFT models.

BACKGROUND: Neisseria meningitides, Streptococcus pneumonia, and hemophilic influenza type B are frequently linked to bacterial meningitis (BM) in children. It's an infectious sickness that kills and severely mobilizes children. For a variety of reasons, bacterial meningitis remains a global public health concern; most cases and deaths are found in Sub-Saharan Africa, particularly in Ethiopia. Even though vaccination has made BM more preventable, children worldwide are still severely harmed by this serious illness. Age, sex, and co-morbidity are among the risk variables for BM that have been found. Therefore, the main objective of this study was to identify the variables influencing the time to recovery for children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia. METHOD: A retrospective cohort of 535 children with bacterial meningitis who received antibiotic treatment was the subject of this study. Parametric Shared Frailty ty and the AFT model were employed with log likelihood, BIC, and AIC methods of model selection. The frailty models all employed the patients' kebele as a clustering factor. RESULTS: The number of cases of BM declined in young children during the duration of the 2 year, 11 month study period, but not in the elderly. Streptococcus pneumonia (50%), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. The time to recovery of patients from bacteria was significantly influenced by the covariates male patients (ϕ = 0.927; 95% CI (0.866, 0.984); p-value = 0.014), patients without a vaccination history (ϕ = 0.898; 95% CI (0.834, 0.965); P value = 0.0037), and patients who were not breastfeeding (ϕ = 0.616; 95% CI (0.404, 0.039); P-value = 0.024). The recovery times for male, non-breastfed children with bacterial patients are 7.9 and 48.4% shorter, respectively. In contrast to children with comorbidity, the recovery time for children without comorbidity increased by 8.7%. CONCLUSION: Age group, sex, vaccination status, co-morbidity, breastfeeding, and medication regimen were the main determinant factors for the time to recovery of patients with bacterial meningitis. Patients with co-morbidities require the doctor at Jigjiga University Referral Hospital to pay close attention to them.

Fulminant coronavirus disease 2019 meningitis in Iranian infants: a case series.

BACKGROUND: Pediatric coronavirus disease 2019 infection usually presents with respiratory and gastrointestinal symptoms. In this report we present fulminant meningitis as the main presentation of coronavirus disease 2019 without major signs and symptoms of other organs' involvement in 3 infants. CASES: The first case was a 4 months Iranian male infant with fulminant meningitis as the main presentation of coronavirus disease 2019 without other organ involvement. He was treated as suspected bacterial meningitis but CSF PCR and CSF culture were negative for common meningeal pathogens. On 3rd day, his coronavirus disease 2019 PCR test became positive, while it was negative on 1st day. The second case was a 13 months Iranian male infant with fever, irritability, and photophobia for 24 h before poorly controlled status epilepticus. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. Seizures were controlled with multiple anti-seizure medications. The third case was a 14 months Iranian female infant with fever and seizure1 hour before admission, leading to poorly controlled status epilepticus despite anti-epileptic therapy 10 h after admission. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. He was controlled with multiple anti-seizure medications. CONCLUSION: Meningitis of coronavirus disease 2019 should be considered in severely ill pediatric cases with poorly controlled seizures and RBC in CSF smear. Also, pediatricians can consider corticosteroids, remdesivir, and IVIG therapy in these cases.

[A Case of Bacterial Meningitis in Which Occurrence of Ataxie Optique Led to Detection of a Small Subdural Abscess and Pialitis].

We report the case of a 69-year-old man with bacterial meningitis who presented with ataxie optique in the peripheral part of the left visual field in both hands. A detailed neurological examination with contrast-enhanced brain MRI in the early stage of the clinical course identified a small subdural abscess and pialitis in the right parietal area. A favorable outcome was obtained with antibiotic therapy alone. In a case with higher brain dysfunction of unknown cause in the clinical course of bacterial meningitis, a detailed neurological examination may be helpful to identify the causative site. (Received September 25, 2023; Accepted October 31, 2023; Published March 1, 2024).

Etiology, Clinical Presentation, and Outcomes of Bacterial Meningitis in Adult Patients: A Retrospective Study in Lithuania (2018-2021).

BACKGROUND Bacterial meningitis is a serious and life-threatening condition that requires prompt diagnosis and treatment. This retrospective study aimed to identify causes, presentation, and predictive factors for outcomes of community-acquired bacterial meningitis in 86 adults in Vilnius, Lithuania between 2018 and 2021. MATERIAL AND METHODS We performed a retrospective study of demographic, clinical, and laboratory records of 86 adult patients admitted to Vilnius University Hospital Santaros Clinics with a diagnosis of acute bacterial meningitis during the period of 2018-2021. RESULTS Of 86 patients, 54 (62.79%) were men. The median (Md) age of patients was 58 (range, 18-83) years and the median duration of hospitalization was 20 (range, 3-92) days. Patients were first hospitalized in the Intensive Care Unit (ICU) in 59.3% of cases. The most prevalent concerns were headache (66.28%), febrile temperature (56.98%), general fatigue (53.49%), and confusion/sleepiness (52.33%). Of 57 (66.28%) etiologically confirmed cases, the most prevalent agent was Listeria monocytogenes (29.82%), followed by Streptococcus pneumoniae (28.07%) and Neisseria meningitidis (28.07%). Patients with meningitis caused by L. monocytogenes were the oldest (P=0.003) and had the longest hospitalization (P<0.001). Fatigue was the prominent symptom in patients with meningococcal meningitis (81.2%, P=0.010). Twelve patients (13.95%) have died. Advanced age and low (<100 cells per µL) white blood cell (WBC) count in cerebrospinal fluid (CSF) were associated with lethal outcome, whereas headache was associated with favorable outcome. CONCLUSIONS Clinical characteristics of community-acquired acute bacterial meningitis differ based on etiological factors. Patient age, CSF WBC count, and headache may be significant predictive factors for outcomes of bacterial meningitis.

Performance of Febrile Infant Decision Tools on Hypothermic Infants Evaluated for Infection.

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

RNA sequencing reveals differential long noncoding RNA expression profiles in bacterial and viral meningitis in children.

BACKGROUND: We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children. METHODS: The peripheral blood of five bacterial meningitis patients, five viral meningitis samples, and five healthy individuals were collected for RNA sequencing. Then, the differentially expressed lncRNA and mRNA were detected in bacterial meningitis vs. controls, viral meningitis vs. healthy samples, and bacterial vs. viral meningitis patients. Besides, co-expression and the competing endogenous RNA (ceRNA) networks were constructed. Receiver operating characteristic curve (ROC) analysis was performed. RESULTS: Compared with the control group, 2 lncRNAs and 32 mRNAs were identified in bacterial meningitis patients, and 115 lncRNAs and 54 mRNAs were detected in viral meningitis. Compared with bacterial meningitis, 165 lncRNAs and 765 mRNAs were identified in viral meningitis. 2 lncRNAs and 31 mRNAs were specific to bacterial meningitis, and 115 lncRNAs and 53 mRNAs were specific to viral meningitis. The function enrichment results indicated that these mRNAs were involved in innate immune response, inflammatory response, and immune system process. A total of 8 and 1401 co-expression relationships were respectively found in bacterial and viral meningitis groups. The ceRNA networks contained 1 lncRNA-mRNA pair and 4 miRNA-mRNA pairs in viral meningitis group. GPR68 and KIF5C, identified in bacterial meningitis co-expression analysis, had an area under the curve (AUC) of 1.00, while the AUC of OR52K2 and CCR5 is 0.883 and 0.698, respectively. CONCLUSIONS: Our research is the first to profile the lncRNAs in bacterial and viral meningitis in children and may provide new insight into understanding meningitis regulatory mechanisms.

Performance of large language models on advocating the management of meningitis: a comparative qualitative study.

OBJECTIVES: We aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in healthcare. METHODS: A simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines. RESULTS: A central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs' text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance. DISCUSSION: Latest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM's unique algorithm rather than output length. CONCLUSIONS: Users must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models' comprehension of complex medical scenarios and their ability to provide reliable information.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy.

OBJECTIVES: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. METHODS: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1ß, CRP and procalcitonin concentrations were measured with Luminex technology. RESULTS: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1ß (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). CONCLUSION: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Interleukin-22 Contributes to Blood-Brain Barrier Disruption via STAT3/VEGFA Activation in Escherichia coli Meningitis.

Escherichia coli continues to be the predominant Gram-negative pathogen causing neonatal meningitis worldwide. Inflammatory mediators have been implicated in the pathogenesis of meningitis and are key therapeutic targets. The role of interleukin-22 (IL-22) in various diseases is diverse, with both protective and pathogenic effects. However, little is understood about the mechanisms underlying the damaging effects of IL-22 on the blood-brain barrier (BBB) in E. coli meningitis. We observed that meningitic E. coli infection induced IL-22 expression in the serum and brain of mice. The tight junction proteins (TJPs) components ZO-1, Occludin, and Claudin-5 were degraded in the mouse brain and human brain microvascular endothelial cells (hBMEC) following IL-22 administration. Moreover, the meningitic E. coli-caused increase in BBB permeability in wild-type mice was restored by knocking out IL-22. Mechanistically, IL-22 activated the STAT3-VEGFA signaling cascade in E. coli meningitis, thus eliciting the degradation of TJPs to induce BBB disruption. Our data indicated that IL-22 is an essential host accomplice during E. coli-caused BBB disruption and could be targeted for the therapy of bacterial meningitis.

Distinguishing community-acquired bacterial and viral meningitis: Microbes and biomarkers.

Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.