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Bacterial meningitis

Infectious Disease MONDO:0006670 Meningitis Bacterial Infection

Bacterial meningitis is a severe infection of the meninges caused by invasive bacteria that overcome neurovascular barriers and replicate in the cerebrospinal fluid. The disease is characterized by robust neuroinflammation that damages brain tissue and raises intracranial pressure. Major causative bacteria include Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and Listeria monocytogenes. Pathogenesis involves bacterial entry through the blood-brain barrier or blood-CSF barrier via receptor-mediated transcytosis or paracellular disruption, followed by activation of pattern recognition receptors (TLR2/TLR4), inflammasome activation, and breakdown of tight junctions. Clinical manifestations include headache, fever, neck stiffness, altered mental status, and in severe cases, seizures and focal neurological deficits. Without prompt antibiotic treatment, the case fatality rate approaches 70-100%.

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Mappings
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Definitions
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Inheritance
6
Pathophysiology
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Histopathology
10
Phenotypes
0
Genes
5
Treatments
0
Subtypes
3
Differentials
0
Datasets
2
Trials
⚙

Pathophysiology

6
Bacterial Invasion
Bacteria enter the bloodstream and cross the blood-brain barrier to infect the meninges.
brain microvascular endothelial cell link choroid plexus epithelial cell link
blood-brain barrier link meninges link cerebrospinal fluid link
Show evidence (4 references)
PMID:26804733 SUPPORT
"Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis. The mechanisms by which pneumococci from the bloodstream penetrate the blood-brain barrier to reach the brain are not fully understood."
The reference discusses how Streptococcus pneumoniae can penetrate the blood-brain barrier from the bloodstream, which supports the statement about bacterial meningitis involving bacteria entering the bloodstream and crossing the blood-brain barrier.
PMID:31805229 SUPPORT
"Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules."
This reference explicitly states that microbial penetration of the blood-brain barrier is necessary for the development of bacterial meningitis, supporting the statement.
PMID:27367319 SUPPORT
"If the infection is not controlled at the stage in which the bacterium is in the liver, for instance, due to a severe immunodepression, a secondary bacteraemia can be developed and L. monocytogenes reaches the preferred sites transgressing the blood-brain barrier or the placental barrier."
The reference mentions that Listeria monocytogenes can cross the blood-brain barrier after entering the bloodstream, which supports the statement about the process of bacterial invasion in meningitis.
+ 1 more reference
Inflammation
Bacterial components trigger a strong inflammatory response in the subarachnoid space.
microglial cell link astrocyte link neutrophil link
inflammatory response link innate immune response link
subarachnoid space link
Show evidence (3 references)
PMID:39116800 SUPPORT
"Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization..."
The reference describes how bacterial meningitis triggers several inflammatory pathways leading to the release of cytokines and chemokines, supporting the statement that bacterial components trigger a strong inflammatory response in the subarachnoid space.
PMID:37544134 SUPPORT
"The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections."
The reference explicitly states that cytokines modulate the inflammatory response in the subarachnoid space during bacterial meningitis, supporting the statement.
PMID:24412248 SUPPORT
"Complement factors C1q and MBL as well as common complement pathway factors C3a, iC3b, C5a, sC5b-9 and complement regulator CFH were all elevated in patients with bacterial meningitis as compared to the controls."
The reference mentions the elevation of complement factors, which are part of the immune response, supporting the idea that bacterial components trigger a strong inflammatory response in the subarachnoid space.
Increased Intracranial Pressure
Inflammation and accumulation of purulent exudate lead to increased intracranial pressure.
brain link cerebrospinal fluid link
Show evidence (4 references)
PMID:2498090 SUPPORT
"Their presence in the cerebrospinal fluid is associated with the induction of inflammation and with the development of brain edema and increased intracranial pressure."
The literature supports that inflammation in bacterial meningitis is associated with increased intracranial pressure.
PMID:24413408 SUPPORT
"Fulminant bacterial meningitis is a rare host reaction to infection characterized by sudden onset, rapid deterioration, abrupt cerebral edema and refractory intracranial hypertension."
This supports the statement that bacterial meningitis can lead to increased intracranial pressure due to inflammation.
PMID:31378869 NO_EVIDENCE
"Acute bacterial meningitis may present with symptoms as nonspecific as headache and fever, but rapid progression to an altered level of consciousness is not unusual."
The literature mentions altered mental status as a downstream effect of bacterial meningitis, supporting the statement.
+ 1 more reference
TLR-Mediated Innate Immune Activation
Pattern recognition receptors TLR2 and TLR4 recognize bacterial components and initiate NF-kB-dependent cytokine responses.
microglial cell link astrocyte link brain microvascular endothelial cell link
TLR2 link TLR4 link
toll-like receptor signaling pathway link I-kappaB kinase/NF-kappaB signaling link
blood-brain barrier link meninges link
Show evidence (2 references)
PMID:39116800 SUPPORT
"Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs)."
Describes BBB-breaching bacteria activating TLR signaling during meningitis, matching the TLR-driven innate activation described in this node.
PMID:16785556 SUPPORT
"We show that both heat-inactivated whole GBS and a secreted proteinaceous factor from GBS (GBS-F) induce neuronal apoptosis via the activation of murine microglia through a TLR2-dependent and MyD88-dependent pathway in vitro."
Shows meningitis-causing GBS activating microglial TLR2/MyD88 signaling and causing neuronal injury, directly supporting TLR-driven innate activation in the CNS.
Inflammasome Activation and Pyroptosis
NLRP3 inflammasome activation drives caspase-1-mediated IL-1beta and IL-18 maturation and pyroptotic cell death, amplifying inflammation and tissue injury.
microglial cell link macrophage link
NLRP3 link CASP1 link
inflammasome complex assembly link pyroptosis link
brain link cerebrospinal fluid link
Show evidence (3 references)
PMID:39116800 SUPPORT
"The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1β and IL-18, hence potentiating neuroinflammation."
States that NLRP3 inflammasome activation in bacterial meningitis drives IL-1β/IL-18 maturation, consistent with inflammasome-driven pyroptotic inflammation.
PMID:37603152 SUPPORT
"The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels."
Experimental pneumococcal meningitis shows NLRP3 upregulation that is blunted by an NLRP3 inhibitor, supporting inflammasome-driven pathology.
PMID:37001294 SUPPORT
"We found that the formation of the NEK7-NLRP3 complex significantly increased during S. pneumoniae infection and that anaplastic lymphoma kinase (ALK) and Jun N-terminal kinase (JNK) were phosphorylated rapidly."
Shows pneumococcal infection driving NEK7-NLRP3 inflammasome assembly through ALK/JNK signaling, supporting inflammasome activation in meningitis.
Blood-Brain Barrier Disruption
Host inflammatory signaling and bacterial virulence factors cause breakdown of tight junctions and increased vascular permeability.
brain microvascular endothelial cell link
IL22 link STAT3 link VEGFA link EGR1 link MMP9 link
JAK-STAT cascade link VEGF-activated receptor activity link tight junction organization link extracellular matrix disassembly link
blood-brain barrier link
Show evidence (2 references)
PMID:31805229 SUPPORT
"Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules."
Establishes BBB penetration as an early pathogenic step requiring host signaling changes that enable barrier breach, supporting BBB disruption in meningitis pathophysiology.
PMID:36769171 SUPPORT
"A defining feature of the pathogenesis of bacterial meningitis is the increase in BBB permeability."
States BBB permeability rise as central to meningitis pathogenesis, supporting the barrier-disruption node.
⬡

Causal Graph

graph LR
    Increased_Intracranial_Pressure["Increased Intracranial Pressure"]
    Altered_Mental_Status["Altered Mental Status"]
    Seizures["Seizures"]
    Focal_Neurological_Deficits["Focal Neurological Deficits"]

    Increased_Intracranial_Pressure --> Altered_Mental_Status
    Increased_Intracranial_Pressure --> Seizures
    Increased_Intracranial_Pressure --> Focal_Neurological_Deficits

    style Increased_Intracranial_Pressure fill:#dbeafe
    style Altered_Mental_Status fill:#fef3c7
    style Seizures fill:#fef3c7
    style Focal_Neurological_Deficits fill:#fef3c7
●

Phenotypes

10
Ear(1) Eye(1) Metabolism(1) Nervous System(4) Other(3)
Ear 1
Hearing Loss OCCASIONAL Hearing impairment (HP:0000365)
Cochlear inflammation and toxin exposure can lead to sensorineural hearing loss as a sequelae
Show evidence (1 reference)
PMID:33330135 SUPPORT
"More recent data from a meta analysis of corticosteroid use for the treatment of bacterial meningitis found no significant reductions in mortality across 25 studies in H. influenzae meningitis cases treated with adjunctive steroid therapy, but similarly did observe a significant reduction in the..."
Notes hearing loss as a measured sequela in H. influenzae meningitis and shows adjunctive steroids reduce its incidence, supporting inclusion of hearing loss.
Eye 1
Photophobia FREQUENT Photophobia (HP:0000613)
Light sensitivity is a common symptom of meningeal irritation
Show evidence (1 reference)
PMID:20109674 SUPPORT
"Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, vomiting, photophobia, and an altered level of consciousness."
Lists photophobia among typical presenting signs of bacterial meningitis, supporting its frequency.
Metabolism 1
Fever VERY_FREQUENT Fever (HP:0001945)
Show evidence (4 references)
PMID:36720125 SUPPORT
"Fever is the most commonly reported symptom in paediatric patients, occurring in up to 93% of cases. Further, it is possible to observe headache, vomiting and positive meningeal phenomena. The most common symptoms in adults are fever, headache, positive meningeal symptoms and impaired consciousness."
The statement is supported as fever is reported as a very frequent symptom in both pediatric and adult patients with bacterial meningitis.
PMID:6473134 PARTIAL
"The rates of prolonged fever for 10 days or more, persistent fever for 5 to 9 days and secondary fever were 13, 13 and 16%, respectively."
This reference supports the statement by indicating that fever is a common symptom during the treatment of bacterial meningitis, with various durations and patterns observed.
PMID:35436245 PARTIAL
"A 33-day-old previously healthy term female is admitted to the pediatric intensive care unit with fever, lethargy and bulging fontanel."
The case study of a 33-day-old infant with bacterial meningitis presenting with fever supports the statement that fever is a very frequent symptom.
+ 1 more reference
Nervous System 4
Headache VERY_FREQUENT Headache (HP:0002315)
Show evidence (5 references)
PMID:34749918 SUPPORT
"secondary headaches related to life threatening infections are most frequently associated with meningitis."
This reference indicates that headaches are frequently associated with meningitis, supporting the statement that headache is a very frequent symptom in bacterial meningitis.
PMID:36720125 SUPPORT
"The most common symptoms in adults are fever, headache, positive meningeal symptoms and impaired consciousness."
This reference lists headache as one of the most common symptoms in adults with bacterial meningitis, supporting the statement.
PMID:11301494 SUPPORT
"Headache as a cardinal symptom of acute meningitis reflects activation of trigeminal afferents from the meninges."
This reference describes headache as a cardinal symptom of acute meningitis, supporting the statement.
+ 2 more references
Hydrocephalus OCCASIONAL Hydrocephalus (HP:0000238)
Impaired CSF flow from inflammation can lead to hydrocephalus
Show evidence (1 reference)
PMID:27055168 SUPPORT
"Complications such as acute hydrocephalus, brain abscess, and spine abscess can develop."
Identifies acute hydrocephalus as a complication of bacterial meningitis, supporting its inclusion.
Seizures FREQUENT Seizure (HP:0001250)
Show evidence (2 references)
PMID:29889417 PARTIAL
"Seizures should be avoided, the sedation-pain control optimized and ventilation adapted to assure normal oxygenation and normal CO₂ levels."
Identifies seizures as a complication to monitor and prevent during acute bacterial meningitis management, supporting their clinical relevance.
PMID:31378869 PARTIAL
"Brain abscess may initially present only with headache, or as a new-onset seizure or with a focal neurological deficit."
Notes that bacterial CNS infections can present with new-onset seizures, reinforcing seizures as a frequent neurological manifestation.
Focal Neurological Deficits FREQUENT Mental deterioration (HP:0001268)
Show evidence (2 references)
PMID:36472590 SUPPORT
"Up to 24% of those who survive develop chronic neurological sequelae, such as hearing loss or focal neurological deficits."
Reports focal neurological deficits as a common chronic sequela in bacterial meningitis survivors.
PMID:36472590 SUPPORT
"Brain imaging should be performed before lumbar puncture if patients present with altered mental status, focal neurological deficits, papilledema, or history of immunocompromising conditions or central nervous system disease."
Highlights focal neurological deficits as a key presenting sign that guides urgent imaging in suspected bacterial meningitis.
Other 3
Neck Stiffness VERY_FREQUENT
Show evidence (2 references)
PMID:22667193 REFUTE
"Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients."
The literature states that neck stiffness occurs in less than half of the patients, which does not support the claim that it is 'VERY_FREQUENT'.
PMID:28652113 REFUTE
"We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%)..."
The study shows that neck stiffness was present in 36% of late diagnosis cases and 78% of early diagnosis cases, indicating it is not 'VERY_FREQUENT' across all cases.
Altered Mental Status FREQUENT
Show evidence (5 references)
PMID:27741995 SUPPORT
"Patients with CNS infection can present to the ED with nonspecific signs and symptoms, including headache, fever, altered mental status, and behavioral changes."
The literature indicates that altered mental status is a common symptom of CNS infections, including bacterial meningitis.
PMID:23981452 SUPPORT
"The classic triad of bacterial meningitis consists of fever, neck stiffness, and altered mental status; headache is also another common symptom."
Altered mental status is part of the classic triad of symptoms for bacterial meningitis, indicating it is a frequent occurrence.
PMID:29206991 PARTIAL
"BACKGROUND: Malaria and acute bacterial meningitis (ABM) are the leading infectious causes of febrile encephalopathy in malaria endemic settings. The clinical distinction of the two conditions is complicated by overlap in clinical features."
The mention of febrile encephalopathy, which includes altered mental status, as a leading symptom of bacterial meningitis supports the statement.
+ 2 more references
Petechial Rash OCCASIONAL
Particularly with meningococcal meningitis
Show evidence (2 references)
PMID:23830646 SUPPORT
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
This reference indicates that meningococcal meningitis is often accompanied by a petechial rash, supporting the statement.
PMID:1994692 SUPPORT
"A rash with petechiae or purpura, the presence of shock, and a normal or low peripheral leukocyte count continue to be predictors of poor outcome."
This reference mentions that petechial rash is a common symptom in meningococcal infections, supporting the statement.
💊

Treatments

5
Empiric Antibiotic Therapy MAXO:0000058
Broad-spectrum antibiotics (e.g., ceftriaxone, vancomycin) started immediately after lumbar puncture.
Show evidence (4 references)
PMID:3287565 PARTIAL
"The available evidence suggests that if bacterial meningitis is suspected and LP must be delayed, intravenous antibiotics are warranted before CSF is obtained."
This suggests that in cases where lumbar puncture (LP) must be delayed, antibiotics should be administered before LP, but it does not explicitly state that antibiotics should be started immediately after LP.
PMID:30496558 PARTIAL
"The use of empiric vancomycin plus a third-generation cephalosporin for suspected bacterial meningitis has been recommended since 1997."
This reference supports the use of broad-spectrum antibiotics like vancomycin and ceftriaxone for empiric therapy but does not specify the timing related to lumbar puncture.
PMID:20109674 NO_EVIDENCE
"Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained."
This reference emphasizes the initiation of empiric therapy after obtaining blood cultures, not specifically after lumbar puncture.
+ 1 more reference
Targeted Antibiotic Therapy MAXO:0000058
Antibiotics tailored to the specific pathogen once identified.
Show evidence (3 references)
PMID:24073921 PARTIAL
"Outcome critically depends on the rapid initiation of effective antibiotic therapy."
The reference emphasizes the importance of initiating effective antibiotic therapy, which aligns with the concept of tailoring antibiotics to the specific pathogen once identified.
PMID:30468130 SUPPORT
"Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies."
The study discusses the importance of understanding antibiotic resistance profiles to prescribe more effective therapies, supporting the concept of targeted antibiotic therapy.
PMID:15301673 PARTIAL
"Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population."
This reference supports the use of specific antibiotics tailored to the pathogen identified, which is a form of targeted antibiotic therapy.
Dexamethasone MAXO:0000058
Corticosteroid used to reduce inflammation and complications, particularly in pneumococcal meningitis.
Show evidence (3 references)
PMID:10830026 PARTIAL
"Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not..."
The statement is partially supported because dexamethasone is used to reduce inflammation in bacterial meningitis, but there is limited evidence of its benefit in reducing complications, particularly for pneumococcal meningitis.
PMID:31668194 SUPPORT
"Steroids are mandatory in pneumococcal meningitis but not indicated in pneumococcal pneumonia except in the setting of refractory shock."
This reference supports the use of corticosteroids, specifically dexamethasone, in reducing inflammation and complications in pneumococcal meningitis.
PMID:33330135 SUPPORT
"Steroid therapy is beneficial and supported in pathogens such as pneumococcal meningitis and tuberculosis."
This reference supports the use of corticosteroids in pneumococcal meningitis to reduce inflammation and complications.
Supportive Care MAXO:0000950
Fluids, electrolyte management, seizure control, and monitoring of intracranial pressure.
Show evidence (5 references)
PMID:8196986 SUPPORT
"Fluid administration in children with meningitis should be conservative in an attempt to minimize cerebral edema and electrolyte disturbances that frequently complicate the course of meningitis."
This reference supports the aspect of fluid and electrolyte management as part of supportive care in bacterial meningitis.
PMID:16034949 SUPPORT
"Careful management of fluid and electrolyte balance is an important supportive therapy. Both over and under hydration are associated with adverse outcomes."
This reference supports the importance of fluid and electrolyte management in the supportive care of bacterial meningitis.
PMID:29889417 SUPPORT
"Control of intracranial pressure (ICP) as well as a good hemodynamic is based on a continuous monitoring of ICP and arterial pressure in order to assure an adapted cerebral perfusion pressure."
This reference supports the monitoring of intracranial pressure as part of the supportive care in bacterial meningitis.
+ 2 more references
Vaccination MAXO:0001017
Vaccines available for prevention of meningococcal, pneumococcal, and Hib meningitis.
Show evidence (5 references)
PMID:15802609 SUPPORT
"Effective routine immunization against Hib, pneumococcus and serogroupC meningococcus has had a significant impact on both invasive disease and carriage caused by these encapsulated bacteria."
This reference confirms that vaccines are available for the prevention of meningococcal, pneumococcal, and Hib meningitis.
PMID:26904695 SUPPORT
"The Hib conjugate vaccine is considered protective and safe."
This reference supports the availability and effectiveness of the Hib vaccine.
PMID:10470562 SUPPORT
"A comprehensive review of all major agents causing bacterial meningitis--meningococcus of the groups A, B, C, W135, and Y, pneumococcus, and Haemophilus influenzae type B (Hib)--is done in terms of preventing them by chemoprophylaxis or vaccination."
This reference supports the availability of vaccines for meningococcal, pneumococcal, and Hib meningitis.
+ 2 more references
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Bacterial meningitis:

Viral Meningitis Not Yet Curated MONDO:0007015
Overlapping Features Aseptic meningitis with lower inflammatory biomarkers and typically milder CSF abnormalities.
Distinguishing Features
  • Lower mean platelet volume compared to bacterial meningitis.
  • Higher CSF/serum glucose ratio and lower neutrophil-to-lymphocyte ratio than bacterial meningitis.
  • Host-response biomarkers (e.g., procalcitonin, CRP) help rule out bacterial causes.
Show evidence (3 references)
PMID:38084680 SUPPORT
"The bacterial meningitis group showed a significantly higher median MPV of 10.9... compared to the viral meningitis group with 8.4... fL (p < 0.0001)."
Demonstrates lower MPV in viral meningitis relative to bacterial meningitis.
PMID:37392600 SUPPORT
"Bacterial meningitis score, cerebrospinal fluid (CSF)/serum glucose ratio, and CSF/serum albumin ratio had the highest area under the curves... for discriminating bacterial meningitis... NLR can be used as a biomarker to differentiate bacterial meningitis from viral meningitis."
Shows NLR and CSF/serum glucose help separate bacterial from viral meningitis.
PMID:38307149 SUPPORT
"Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis... host protein biomarkers, such as procalcitonin and C-reactive protein..."
Notes host-response biomarkers used to distinguish viral from bacterial meningitis.
Tuberculous Meningitis Not Yet Curated MONDO:0006042
Overlapping Features Subacute meningeal infection from Mycobacterium tuberculosis with lower D-dimer and CRP than acute bacterial meningitis.
Distinguishing Features
  • D-dimer and CRP levels lower than in acute bacterial meningitis; combined testing improves discrimination.
  • Often subacute course with lymphocytic CSF profile and basal meningeal enhancement.
Show evidence (1 reference)
PMID:34390335 SUPPORT
"The levels of D-dimer and CRP in the BM group were significantly higher than those levels in the TM group... the combined detection of the 2 markers was 86.3% to 100%..."
Combined D-dimer and CRP differentiates bacterial from tuberculous meningitis.
Encephalitis or Cerebritis/Abscess Not Yet Curated MONDO:0019956
Overlapping Features Parenchymal infection or inflammation with focal lesions rather than isolated meningeal involvement.
Distinguishing Features
  • Neuroimaging shows parenchymal diffusion restriction or ring-enhancing lesions (cerebritis/abscess) rather than isolated meningeal enhancement.
  • May present with focal neurologic deficits or seizures without classic meningeal CSF pattern.
Show evidence (1 reference)
PMID:36404039 SUPPORT
"describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis."
Highlights imaging patterns that separate meningitis from parenchymal infections like cerebritis or abscess.
🔬

Clinical Trials

2
NCT02591290 PHASE_IV COMPLETED
Two-dose MenACWY (Menactra) immunogenicity and safety in healthy Japanese adults.
Show evidence (1 reference)
clinicaltrials:NCT02591290 SUPPORT
"evaluate and describe the immune responses to meningococcal antigens (serogroups A,C, Y and W-135) at 28 days following each vaccination with SP284 vaccine"
MenACWY conjugate vaccine immune response data relevant to bacterial meningitis prevention.
NCT07062445 NOT_APPLICABLE NOT_RECRUITING
Prospective Brazilian pediatric registry capturing acute treatment and long-term outcomes in infectious meningitis.
Show evidence (1 reference)
clinicaltrials:NCT07062445 SUPPORT
"Prospective, multicenter, observational clinical registry of pediatric patients with acute infectious meningitis"
Real-world registry to characterize management and outcomes in pediatric meningitis, informing care protocols.
{ }

Source YAML

click to show 
name: Bacterial meningitis
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-02-16T20:19:38Z'
category: Infectious Disease
description: Bacterial meningitis is a severe infection of the meninges caused by invasive bacteria that overcome neurovascular barriers and replicate in the cerebrospinal fluid. The disease is characterized by robust neuroinflammation that damages brain tissue and raises intracranial pressure. Major causative bacteria include Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and Listeria monocytogenes. Pathogenesis involves bacterial entry through the blood-brain barrier or blood-CSF barrier via receptor-mediated transcytosis or paracellular disruption, followed by activation of pattern recognition receptors (TLR2/TLR4), inflammasome activation, and breakdown of tight junctions. Clinical manifestations include headache, fever, neck stiffness, altered mental status, and in severe cases, seizures and focal neurological deficits. Without prompt antibiotic treatment, the case fatality rate approaches 70-100%.
parents:
- Meningitis
- Bacterial Infection
infectious_agent:
- name: Neisseria meningitidis
  infectious_agent_term:
    preferred_term: Neisseria meningitidis
    term:
      id: NCBITaxon:487
      label: Neisseria meningitidis
  description: A common cause of bacterial meningitis, particularly in children and young adults.
  evidence:
  - reference: PMID:17696042
    supports: SUPPORT
    snippet: Neisseria meningitidis is the most common cause of meningitis in children aged 2-18 with a mortality rate ranging from 4-40% and substantial morbidity in 11-19% of survivors.
    explanation: The literature states that Neisseria meningitidis is the most common
  - reference: PMID:38524112
    supports: SUPPORT
    snippet: This meningococcal meningitis cluster caused by Neisseria meningitidis serogroup C occurred among non-vaccinated persons mostly aged <18 years in Palorinya Refugee Settlement.
    explanation: The literature mentions a cluster of meningitis cases caused by Neisseria meningitidis in a population mostly under 18 years old, supporting the statement that it is a common cause of bacterial meningitis in children and young adults.
- name: Streptococcus pneumoniae
  infectious_agent_term:
    preferred_term: Streptococcus pneumoniae
    term:
      id: NCBITaxon:1313
      label: Streptococcus pneumoniae
  description: The most common cause of bacterial meningitis in adults.
  evidence:
  - reference: PMID:9519033
    supports: SUPPORT
    snippet: S pneumoniae is now the most common cause in children and adults overall.
    explanation: The reference clearly states that Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults.
  - reference: PMID:30873934
    supports: SUPPORT
    snippet: "Streptococcus pneumoniae (the pneumoccus) is the leading cause of otitis media, community-acquired pneumonia, and bacterial meningitis."
    explanation: The reference confirms that Streptococcus pneumoniae is the leading cause of bacterial meningitis.
  - reference: PMID:24568594
    supports: SUPPORT
    snippet: The most common causative organisms were Neisseria meningitidis (41%) and Streptococcus pneumoniae (30%).
    explanation: The reference indicates that Streptococcus pneumoniae is one of the most common causes of bacterial meningitis in adults, supporting the statement.
- name: Haemophilus influenzae
  infectious_agent_term:
    preferred_term: Haemophilus influenzae
    term:
      id: NCBITaxon:727
  description: Was a common cause in children before the Hib vaccine.
  evidence:
  - reference: PMID:11032188
    supports: SUPPORT
    snippet: Hib was the most common cause of bacterial meningitis and other invasive bacterial diseases in this age group.
    explanation: The reference indicates that Haemophilus influenzae type b (Hib) was the most common cause of bacterial meningitis in children before the Hib vaccine was introduced.
  - reference: PMID:15907145
    supports: SUPPORT
    snippet: Recently, Haemophilus influenzae type b (Hib), once a common cause of meningitis, has virtually disappeared in developed nations, reflecting the overwhelming success of Hib vaccination.
    explanation: This reference supports the statement by noting that Hib was once a common cause of meningitis before the introduction of the Hib vaccine.
  - reference: PMID:31981610
    supports: SUPPORT
    snippet: H. influenzae type b is the leading cause of bacterial meningitis in children before introduction of vaccination.
    explanation: This reference clearly states that Haemophilus influenzae type b was the leading cause of bacterial meningitis in children before the vaccine was introduced.
- name: Listeria monocytogenes
  infectious_agent_term:
    preferred_term: Listeria monocytogenes
    term:
      id: NCBITaxon:1639
      label: Listeria monocytogenes
  description: Can cause meningitis in newborns, pregnant women, and immunocompromised individuals.
  evidence:
  - reference: PMID:13904618
    supports: SUPPORT
    snippet: Listeria monocytogenes meningitis in neonates.
    explanation: This reference specifically mentions Listeria monocytogenes causing meningitis in neonates.
  - reference: PMID:33583696
    supports: SUPPORT
    snippet: Listeria monocytogenes is a foodborne pathogen responsible for listeriosis, an infection that can manifest in humans as bacteremia, meningoencephalitis in immunocompromised patients and the elderly, and fetal-placental infection in pregnant women.
    explanation: This reference supports the statement by indicating that Listeria monocytogenes can cause meningoencephalitis in immunocompromised patients and fetal-placental infection in pregnant women.
  - reference: PMID:28536811
    supports: SUPPORT
    snippet: Listeria has a predilection to affect immunocompromised patients, elderly people, pregnant women and neonates.
    explanation: This reference supports the statement by indicating that Listeria monocytogenes affects immunocompromised patients, pregnant women, and neonates.
  - reference: PMID:27055168
    supports: SUPPORT
    snippet: Listeria monocytogenes may cause meningitis, meningoencephalitis, brain abscess, pyogenic arthritis, osteomyelitis, and liver abscess in children.
    explanation: This reference supports the statement by indicating that Listeria monocytogenes can cause meningitis in children, which includes newborns.
  - reference: PMID:6349348
    supports: SUPPORT
    snippet: Predominant pathogens are Escherichia coli, group B streptococci, Listeria monocytogenes, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.
    explanation: This reference supports the statement by listing Listeria monocytogenes as a predominant pathogen in bacterial meningitis.
  - reference: PMID:10470563
    supports: NO_EVIDENCE
    snippet: Bacterial pathogens primarily are associated with the maternal genitourinary tract.
    explanation: This reference supports the statement by associating bacterial meningitis in neonates with maternal genitourinary tract pathogens, which includes Listeria monocytogenes.
transmission:
- name: Respiratory Droplets
  description: Spread through close contact with an infected person, such as coughing or sneezing.
  evidence:
  - reference: PMID:22667193
    supports: NO_EVIDENCE
    snippet: Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis.
    explanation: The provided reference does not mention the spread of bacterial meningitis through respiratory droplets or close contact.
  - reference: PMID:8449848
    supports: NO_EVIDENCE
    snippet: 'Chemoprophylaxis can be used only for the prevention of secondary cases once an index case has been identified. The objectives of prophylaxis are threefold: (i) to eliminate nasopharyngeal carriage in household contacts; (ii) to prevent contacts from acquiring the disease and (iii) to treat infection in those incubating the disease.'
    explanation: The focus is on chemoprophylaxis and nasopharyngeal carriage but does not provide direct evidence regarding transmission through respiratory droplets.
  - reference: PMID:31981610
    supports: NO_EVIDENCE
    snippet: H. influenzae type b is the leading cause of bacterial meningitis in children before introduction of vaccination and is a common cause of pneumonia, epiglottis and septic arthritis.
    explanation: The reference discusses the causes and impacts of Haemophilus influenzae but does not provide information on the transmission of bacterial meningitis through respiratory droplets.
prevalence:
- population: Global
  percentage: Variable, higher in regions with lower vaccination rates
  evidence:
  - reference: PMID:26453240
    supports: PARTIAL
    snippet: Most countries had a yearly invasive NmB incidence of less than 2 per 100,000 people. Within these relatively low incidence rates (compared with common causes of invasive bacterial diseases), substantial variation was detected between countries, with a notably higher incidence in Australia, Europe, North America, and South America. China and India had reports only of sporadic cases, and except for South Africa, sub-Saharan Africa showed a near absence of disease.
    explanation: The study highlights substantial variation in NmB incidence between countries, which can be influenced by vaccination rates among other factors.
  - reference: PMID:34718466
    supports: PARTIAL
    snippet: Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.
    explanation: Low vaccination rates among patients with complement component deficiencies in the US suggest that regions with lower vaccination rates may have higher incidences of bacterial meningitis.
  - reference: PMID:36117004
    supports: PARTIAL
    snippet: Coverage of the second dose of MenB vaccine at 12 months was >92% in 2017/18, but this may mask inequalities in coverage in particular population groups. MenB vaccination records for children aged six, 12 and 18 months of age from December 2016 to May 2018 were routinely extracted from GP patient management systems every month in England via a web-based platform for national monitoring of vaccine coverage.
    explanation: This study indicates that while overall vaccination rates may be high, there are inequalities in coverage among different population groups, which can lead to variable rates of bacterial meningitis.
  - reference: PMID:31640619
    supports: PARTIAL
    snippet: Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis were the most leading pathogens causing bacterial meningitis, accounted for 266(23.44%), 145(12.78%), 95(8.37%) of cases, respectively. Each of the three bacterial species showed a descending trend. The majority of infected subjects are children under five years.
    explanation: This study shows the prevalence of bacterial meningitis pathogens in Iran before the introduction of vaccines, supporting the idea that vaccination rates impact the incidence of bacterial meningitis.
  - reference: PMID:3130424
    supports: PARTIAL
    snippet: During the first pre-vaccination survey, performed during an outbreak of meningococcal disease, the carriage rate was high (16%). The carriage rate remained high during a second survey made 6 months after a vaccination campaign that covered approximately 90% of the study population. A year later very few group A meningococcal carriers were found.
    explanation: While the vaccination campaign did not immediately reduce the carriage rate, it eventually led to a significant decrease in group A meningococcal carriers, indicating that vaccination can influence meningococcal disease rates over time.
- population: Infants and Young Children
  notes: At higher risk, particularly if not vaccinated
  evidence:
  - reference: PMID:16342836
    supports: SUPPORT
    snippet: Serogroup B accounts for the highest incidence of disease in young infants but is not contained in any vaccine licensed in the United States.
    explanation: The abstract indicates that young infants have the highest incidence of meningococcal disease caused by serogroup B, supporting the statement that infants and young children are at higher risk, particularly if not vaccinated.
  - reference: PMID:28301990
    supports: PARTIAL
    snippet: We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults.
    explanation: The study identifies age as a risk factor for bacterial meningitis, supporting the statement that infants and young children are at higher risk.
  - reference: PMID:18820360
    supports: SUPPORT
    snippet: Our data are the first minimal estimate of the incidence of Hib meningitis for Indian children. The observed incidence data are similar to European reports before Hib vaccine use, suggest substantial disease before 24 months of age, and provide data useful for policy regarding Hib immunization.
    explanation: The study provides incidence data for Hib meningitis, showing substantial disease in children before 24 months of age, supporting the statement that infants and young children are at higher risk if not vaccinated.
  - reference: PMID:36117004
    supports: PARTIAL
    snippet: In England, the Meningitis B (MenB) vaccine is scheduled at eight and 16 weeks with a booster dose at one year of age and protects children against invasive bacterial meningococcal disease caused by Neisseria meningitidis serogroup B.
    explanation: The abstract mentions the vaccination schedule for MenB and its role in protecting children against invasive bacterial meningococcal disease, supporting the statement that infants and young children are at higher risk if not vaccinated.
  - reference: PMID:34469553
    supports: PARTIAL
    snippet: We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010-2012) and post- (2014-2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia.
    explanation: The study investigates bacterial meningitis in children under 5 years, supporting the statement that infants and young children are at higher risk, particularly if not vaccinated.
- population: Elderly
  notes: At increased risk due to weakened immune system
  evidence:
  - reference: PMID:6466018
    supports: SUPPORT
    snippet: Meningitis in the elderly is likely to be bacterial and to cause greater morbidity and mortality.
    explanation: The study indicates that elderly patients have a high incidence of bacterial meningitis with serious complications and high mortality, which supports the statement that the elderly population is at increased risk due to a weakened immune system.
  - reference: PMID:6372470
    supports: SUPPORT
    snippet: 'Certain host factors increase the risk of acquiring meningitis and include: age (increased at extremes of life)...'
    explanation: The reference mentions age as a risk factor for bacterial meningitis, which supports the statement that the elderly are at increased risk.
- population: Immunocompromised Individuals
  notes: More susceptible to bacterial meningitis
  evidence:
  - reference: PMID:1610138
    supports: PARTIAL
    snippet: Bacterial meningitis in the immunocompromised host.
    explanation: The title of the reference directly indicates a focus on bacterial meningitis in immunocompromised individuals, suggesting they are more susceptible.
  - reference: PMID:31830496
    supports: SUPPORT
    snippet: GBS meningitis in adults mainly occurs in those with underlying conditions such as immunocompromised state, CSF leakage, and endocarditis.
    explanation: The study indicates that GBS meningitis in adults is more common in those with an immunocompromised state, supporting the statement.
  - reference: PMID:36472590
    supports: SUPPORT
    snippet: In adults, risk factors for bacterial meningitis include older age and immunosuppressive conditions.
    explanation: The abstract mentions immunosuppressive conditions as a risk factor for bacterial meningitis, supporting the statement.
epidemiology:
- name: Incidence, Developed Countries
  unit: cases per 100,000 population per year
  minimum_value: 0.1
  maximum_value: 1
  evidence:
  - reference: PMID:31495596
    supports: PARTIAL
    snippet: In the Tel Aviv District, the incidence rates ranged from 0.4 to 1.4 cases per 100,000 population per year during 2007-2017.
    explanation: The incidence of invasive meningococcal disease in the Tel Aviv District falls within the range of 0.1 to 1 cases per 100,000 population per year mentioned in the statement, but it slightly exceeds the maximum value of 1 in some years.
  - reference: PMID:26453240
    supports: PARTIAL
    snippet: Most countries had a yearly invasive NmB incidence of less than 2 per 100,000 people. Within these relatively low incidence rates (compared with common causes of invasive bacterial diseases), substantial variation was detected between countries, with a notably higher incidence in Australia, Europe, North America, and South America.
    explanation: The statement is partially supported as the incidence in developed countries is generally low but can exceed the maximum value of 1 case per 100,000 population per year in some regions.
- name: Incidence, Developing Countries
  unit: cases per 100,000 population per year
  minimum_value: 1
  maximum_value: 10
  notes: Higher incidence due to lower vaccination rates and crowded living conditions
  evidence:
  - reference: PMID:8333768
    supports: PARTIAL
    snippet: This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1).
    explanation: The incidence rate of bacterial meningitis in the Nottingham District Health Authority area is higher than the stated range of 1 to 10 cases per 100,000 population per year. However, this reference does not specifically address developing countries.
  - reference: PMID:18181445
    supports: PARTIAL
    snippet: The Hib meningitis annual incidence in three PICs was 70 to 84 per 100,000 children under five years.
    explanation: The incidence rate of Hib meningitis in Pacific island countries is significantly higher than the stated range of 1 to 10 cases per 100,000 population per year. This suggests that bacterial meningitis can have a higher incidence in certain developing regions, though it does not provide a comprehensive view across all developing countries.
  - reference: PMID:31671441
    supports: PARTIAL
    snippet: Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3.
    explanation: The average annual incidences for different bacterial causes of meningitis in the African meningitis belt fall within the stated range of 1 to 10 cases per 100,000 population per year, supporting the statement partially.
- name: Case Fatality Rate, Treated
  unit: percentage
  minimum_value: 10
  maximum_value: 15
  evidence:
  - reference: PMID:27345176
    supports: NO_EVIDENCE
    snippet: Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment.
    explanation: The study focuses on Listeria monocytogenes infections and does not provide specific information on the overall case fatality rate for bacterial meningitis.
  - reference: PMID:24568594
    supports: NO_EVIDENCE
    snippet: 'INTRODUCTION: Bacterial meningitis is a serious disease with a mortality rate of 15-20% in adults.'
    explanation: The study mentions a case fatality rate of 15-20% in adults, which does not directly support the statement that the treated case fatality rate is between 10% and 15%.
  - reference: PMID:34343128
    supports: NO_EVIDENCE
    snippet: The crude CFR of neonatal meningitis was 32%.
    explanation: The study provides a case fatality rate of 32% for neonatal meningitis, which is not within the range specified in the statement.
- name: Case Fatality Rate, Untreated
  unit: percentage
  minimum_value: 70
  maximum_value: 100
  evidence:
  - reference: PMID:36190396
    supports: NO_EVIDENCE
    snippet: The observed mortality was 33% (38/114 patients).
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:24568594
    supports: NO_EVIDENCE
    snippet: Bacterial meningitis is a serious disease with a mortality rate of 15-20% in adults.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:27345176
    supports: NO_EVIDENCE
    snippet: Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:25442861
    supports: NO_EVIDENCE
    snippet: A total of 175 children with confirmed bacterial meningitis were enrolled.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:18254060
    supports: NO_EVIDENCE
    snippet: Acute bacterial meningitis remains a disease with high mortality and morbidity rates.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:34343128
    supports: NO_EVIDENCE
    snippet: The crude CFR of neonatal meningitis was 32%.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:20485712
    supports: NO_EVIDENCE
    snippet: Meningococcal disease remains a significant illness with an overall mortality of around 8%.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:20453662
    supports: NO_EVIDENCE
    snippet: BM in cirrhotic patients is associated with a high mortality rate.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
  - reference: PMID:22029523
    supports: NO_EVIDENCE
    snippet: Despite targeted therapy, case-fatality rates and neurologic sequelae of bacterial meningitis remain unacceptably high.
    explanation: This study provides data on treated cases of bacterial meningitis, not untreated cases.
progression:
- phase: Colonization and Bacteremia
  notes: Bacteria colonize the nasopharynx or gut and enter the bloodstream. Initial infection often occurs at mucosal surfaces before systemic invasion.
  evidence:
  - reference: PMID:27367319
    supports: SUPPORT
    snippet: "If the infection is not controlled at the stage in which the bacterium is in the liver... a secondary bacteraemia can be developed and L. monocytogenes reaches the preferred sites transgressing the blood-brain barrier."
    explanation: Describes bacteremia developing after initial mucosal infection, providing the bloodstream phase that precedes CNS invasion.
- phase: CNS Barrier Penetration
  notes: Bacteria cross the blood-brain barrier or blood-CSF barrier through transcellular or paracellular routes. Entry mechanisms include receptor-mediated endocytosis (PAFR, PIGR, PECAM1), paracellular disruption via inflammatory signaling (NF-kB, HIF-1a/VEGFA, IL-22/STAT3), or transcytosis across choroid plexus epithelium.
  evidence:
  - reference: PMID:31805229
    supports: SUPPORT
    snippet: "Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules."
    explanation: Establishes BBB penetration as the required step to initiate meningitis.
- phase: CSF Proliferation
  notes: Rapid bacterial replication in cerebrospinal fluid where innate defenses are limited. CSF has markedly low complement concentrations, enabling rapid pathogen expansion.
  evidence:
  - reference: PMID:37544134
    supports: PARTIAL
    snippet: "In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum."
    explanation: Elevated CSF cytokines reflect heavy intrathecal bacterial load and immune activation consistent with rapid CSF proliferation.
- phase: Innate Immune Activation
  notes: Pattern recognition receptors (TLR2/TLR4) and inflammasomes (NLRP3) activate inflammatory cascades. Both canonical (caspase-1) and non-canonical (caspase-11) inflammasome pathways may be activated depending on pathogen.
  evidence:
  - reference: PMID:39116800
    supports: SUPPORT
    snippet: "after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling... that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1β, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation."
    explanation: Shows TLR-driven innate signaling and cytokine release after BBB breach.
- phase: Barrier Breakdown and Neuroinflammation
  notes: Tight junction disruption, microglial and astrocyte activation, neutrophil recruitment, and complement activation. Mediated by cytokines, chemokines, MMPs, and bacterial toxins such as pneumolysin.
  evidence:
  - reference: PMID:39116800
    supports: SUPPORT
    snippet: "these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling... NF-κB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1β, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation."
    explanation: Details inflammatory signaling cascades that drive barrier injury and neuroinflammation.
- phase: Elevated ICP and Tissue Damage
  notes: Vasogenic and cytotoxic edema lead to increased intracranial pressure, ischemic complications, and neuronal injury. Common complications include seizures, altered mental status, focal deficits, hearing loss, and hydrocephalus.
  evidence:
  - reference: PMID:2498090
    supports: SUPPORT
    snippet: "presence in the cerebrospinal fluid is associated with the induction of inflammation and with the development of brain edema and increased intracranial pressure."
    explanation: Links CSF bacterial products to brain edema and raised intracranial pressure, driving neurological complications.
pathophysiology:
- name: Bacterial Invasion
  description: Bacteria enter the bloodstream and cross the blood-brain barrier to infect the meninges.
  locations:
  - preferred_term: blood-brain barrier
    term:
      id: UBERON:0000120
      label: blood-brain barrier
  - preferred_term: meninges
    term:
      id: UBERON:0002360
      label: meninges
  - preferred_term: cerebrospinal fluid
    term:
      id: UBERON:0001359
      label: cerebrospinal fluid
  cell_types:
  - preferred_term: brain microvascular endothelial cell
    term:
      id: CL:2000044
      label: brain microvascular endothelial cell
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:26804733
    supports: SUPPORT
    snippet: Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis. The mechanisms by which pneumococci from the bloodstream penetrate the blood-brain barrier to reach the brain are not fully understood.
    explanation: The reference discusses how Streptococcus pneumoniae can penetrate the blood-brain barrier from the bloodstream, which supports the statement about bacterial meningitis involving bacteria entering the bloodstream and crossing the blood-brain barrier.
  - reference: PMID:31805229
    supports: SUPPORT
    snippet: Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules.
    explanation: This reference explicitly states that microbial penetration of the blood-brain barrier is necessary for the development of bacterial meningitis, supporting the statement.
  - reference: PMID:27367319
    supports: SUPPORT
    snippet: If the infection is not controlled at the stage in which the bacterium is in the liver, for instance, due to a severe immunodepression, a secondary bacteraemia can be developed and L. monocytogenes reaches the preferred sites transgressing the blood-brain barrier or the placental barrier.
    explanation: The reference mentions that Listeria monocytogenes can cross the blood-brain barrier after entering the bloodstream, which supports the statement about the process of bacterial invasion in meningitis.
  - reference: PMID:11008113
    supports: SUPPORT
    snippet: Transcellular penetration, e.g., transcytosis across the BBB has been demonstrated for Escherichia coli K1, group B streptococcus, Listeria monocytogenes, Citrobacter freundii and Streptococcus pneumonia strains.
    explanation: Highlights BBB transcytosis by common neonatal and adult meningitis pathogens, reinforcing the invasion step across brain microvascular endothelium.
- name: Inflammation
  description: Bacterial components trigger a strong inflammatory response in the subarachnoid space.
  locations:
  - preferred_term: subarachnoid space
    term:
      id: UBERON:0001496
      label: subarachnoid space
  cell_types:
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  chemical_entities:
  - preferred_term: Cytokines
    term:
      id: CHEBI:59527
      label: cytokine
  - preferred_term: Chemokines
    term:
      id: CHEBI:80222
      label: chemokine
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: innate immune response
    term:
      id: GO:0045087
      label: innate immune response
  evidence:
  - reference: PMID:39116800
    supports: SUPPORT
    snippet: Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization domain (NOD)-like receptor-mediated signaling, pneumolysin related signaling, NF-kappaB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1beta, tumor necrosis factor(TNF)-alpha, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation.
    explanation: The reference describes how bacterial meningitis triggers several inflammatory pathways leading to the release of cytokines and chemokines, supporting the statement that bacterial components trigger a strong inflammatory response in the subarachnoid space.
  - reference: PMID:37544134
    supports: SUPPORT
    snippet: The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections.
    explanation: The reference explicitly states that cytokines modulate the inflammatory response in the subarachnoid space during bacterial meningitis, supporting the statement.
  - reference: PMID:24412248
    supports: SUPPORT
    snippet: Complement factors C1q and MBL as well as common complement pathway factors C3a, iC3b, C5a, sC5b-9 and complement regulator CFH were all elevated in patients with bacterial meningitis as compared to the controls.
    explanation: The reference mentions the elevation of complement factors, which are part of the immune response, supporting the idea that bacterial components trigger a strong inflammatory response in the subarachnoid space.
- name: Increased Intracranial Pressure
  description: Inflammation and accumulation of purulent exudate lead to increased intracranial pressure.
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: cerebrospinal fluid
    term:
      id: UBERON:0001359
      label: cerebrospinal fluid
  downstream:
  - target: Altered Mental Status
  - target: Seizures
  - target: Focal Neurological Deficits
  evidence:
  - reference: PMID:2498090
    supports: SUPPORT
    snippet: Their presence in the cerebrospinal fluid is associated with the induction of inflammation and with the development of brain edema and increased intracranial pressure.
    explanation: The literature supports that inflammation in bacterial meningitis is associated with increased intracranial pressure.
  - reference: PMID:24413408
    supports: SUPPORT
    snippet: Fulminant bacterial meningitis is a rare host reaction to infection characterized by sudden onset, rapid deterioration, abrupt cerebral edema and refractory intracranial hypertension.
    explanation: This supports the statement that bacterial meningitis can lead to increased intracranial pressure due to inflammation.
  - reference: PMID:31378869
    supports: NO_EVIDENCE
    snippet: Acute bacterial meningitis may present with symptoms as nonspecific as headache and fever, but rapid progression to an altered level of consciousness is not unusual.
    explanation: The literature mentions altered mental status as a downstream effect of bacterial meningitis, supporting the statement.
  - reference: PMID:8859061
    supports: NO_EVIDENCE
    snippet: The clinical course of bacterial meningitis still is characterized by a high mortality and frequent neurological deficits in survivors.
    explanation: The literature supports that bacterial meningitis can lead to neurological deficits, aligning with the downstream effects mentioned in the statement.
- name: TLR-Mediated Innate Immune Activation
  description: Pattern recognition receptors TLR2 and TLR4 recognize bacterial components and initiate NF-kB-dependent cytokine responses.
  genes:
  - preferred_term: TLR2
    term:
      id: hgnc:11849
      label: TLR2
  - preferred_term: TLR4
    term:
      id: hgnc:11850
      label: TLR4
  locations:
  - preferred_term: blood-brain barrier
    term:
      id: UBERON:0000120
      label: blood-brain barrier
  - preferred_term: meninges
    term:
      id: UBERON:0002360
      label: meninges
  cell_types:
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: brain microvascular endothelial cell
    term:
      id: CL:2000044
      label: brain microvascular endothelial cell
  biological_processes:
  - preferred_term: toll-like receptor signaling pathway
    term:
      id: GO:0002224
      label: toll-like receptor signaling pathway
  - preferred_term: I-kappaB kinase/NF-kappaB signaling
    term:
      id: GO:0007249
      label: I-kappaB kinase/NF-kappaB signaling
  notes: TLR2 recognizes Gram-positive bacterial components while TLR4 recognizes Gram-negative components, initiating inflammatory cascades that both defend against infection and contribute to tissue damage.
  evidence:
  - reference: PMID:39116800
    supports: SUPPORT
    snippet: Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs).
    explanation: Describes BBB-breaching bacteria activating TLR signaling during meningitis, matching the TLR-driven innate activation described in this node.
  - reference: PMID:16785556
    supports: SUPPORT
    snippet: We show that both heat-inactivated whole GBS and a secreted proteinaceous factor from GBS (GBS-F) induce neuronal apoptosis via the activation of murine microglia through a TLR2-dependent and MyD88-dependent pathway in vitro.
    explanation: Shows meningitis-causing GBS activating microglial TLR2/MyD88 signaling and causing neuronal injury, directly supporting TLR-driven innate activation in the CNS.
- name: Inflammasome Activation and Pyroptosis
  description: NLRP3 inflammasome activation drives caspase-1-mediated IL-1beta and IL-18 maturation and pyroptotic cell death, amplifying inflammation and tissue injury.
  genes:
  - preferred_term: NLRP3
    term:
      id: hgnc:16400
      label: NLRP3
  - preferred_term: CASP1
    term:
      id: hgnc:1499
      label: CASP1
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: cerebrospinal fluid
    term:
      id: UBERON:0001359
      label: cerebrospinal fluid
  cell_types:
  - preferred_term: microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: inflammasome complex assembly
    term:
      id: GO:0061702
      label: inflammasome complex assembly
  - preferred_term: pyroptosis
    term:
      id: GO:0070269
      label: pyroptosis
  notes: Meningococcal infection activates both canonical (caspase-1) and non-canonical (caspase-11 in mice) inflammasome pathways, leading to pyroptotic endothelial death.
  evidence:
  - reference: PMID:39116800
    supports: SUPPORT
    snippet: The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1β and IL-18, hence potentiating neuroinflammation.
    explanation: States that NLRP3 inflammasome activation in bacterial meningitis drives IL-1β/IL-18 maturation, consistent with inflammasome-driven pyroptotic inflammation.
  - reference: PMID:37603152
    supports: SUPPORT
    snippet: The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels.
    explanation: Experimental pneumococcal meningitis shows NLRP3 upregulation that is blunted by an NLRP3 inhibitor, supporting inflammasome-driven pathology.
  - reference: PMID:37001294
    supports: SUPPORT
    snippet: We found that the formation of the NEK7-NLRP3 complex significantly increased during S. pneumoniae infection and that anaplastic lymphoma kinase (ALK) and Jun N-terminal kinase (JNK) were phosphorylated rapidly.
    explanation: Shows pneumococcal infection driving NEK7-NLRP3 inflammasome assembly through ALK/JNK signaling, supporting inflammasome activation in meningitis.
- name: Blood-Brain Barrier Disruption
  description: Host inflammatory signaling and bacterial virulence factors cause breakdown of tight junctions and increased vascular permeability.
  genes:
  - preferred_term: IL22
    term:
      id: hgnc:5982
      label: IL22
  - preferred_term: STAT3
    term:
      id: hgnc:11364
      label: STAT3
  - preferred_term: VEGFA
    term:
      id: hgnc:12680
      label: VEGFA
  - preferred_term: EGR1
    term:
      id: hgnc:3238
      label: EGR1
  - preferred_term: MMP9
    term:
      id: hgnc:7176
      label: MMP9
  locations:
  - preferred_term: blood-brain barrier
    term:
      id: UBERON:0000120
      label: blood-brain barrier
  cell_types:
  - preferred_term: brain microvascular endothelial cell
    term:
      id: CL:2000044
      label: brain microvascular endothelial cell
  biological_processes:
  - preferred_term: JAK-STAT cascade
    term:
      id: GO:0007259
      label: JAK-STAT cascade
  - preferred_term: VEGF-activated receptor activity
    term:
      id: GO:0005021
      label: vascular endothelial growth factor-activated receptor activity
  - preferred_term: tight junction organization
    term:
      id: GO:0120193
      label: tight junction organization
  - preferred_term: extracellular matrix disassembly
    term:
      id: GO:0022617
      label: extracellular matrix disassembly
  notes: IL-22 activates STAT3-VEGFA signaling leading to degradation of tight junction proteins (ZO-1, occludin, claudin-5). EGR1 is a master regulator upregulating VEGFA, PDGFB, ANGPTL4 and downregulating tight junctions. MMP9 degrades basement membrane and contributes to paracellular leak.
  evidence:
  - reference: PMID:31805229
    supports: SUPPORT
    snippet: Microbial penetration of the blood-brain barrier, a prerequisite for the development of bacterial meningitis, exploits specific host and bacterial factors as well as host cell signaling molecules.
    explanation: Establishes BBB penetration as an early pathogenic step requiring host signaling changes that enable barrier breach, supporting BBB disruption in meningitis pathophysiology.
  - reference: PMID:36769171
    supports: SUPPORT
    snippet: A defining feature of the pathogenesis of bacterial meningitis is the increase in BBB permeability.
    explanation: States BBB permeability rise as central to meningitis pathogenesis, supporting the barrier-disruption node.
phenotypes:
- category: Neurological
  name: Headache
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:34749918
    supports: SUPPORT
    snippet: secondary headaches related to life threatening infections are most frequently associated with meningitis.
    explanation: This reference indicates that headaches are frequently associated with meningitis, supporting the statement that headache is a very frequent symptom in bacterial meningitis.
  - reference: PMID:36720125
    supports: SUPPORT
    snippet: The most common symptoms in adults are fever, headache, positive meningeal symptoms and impaired consciousness.
    explanation: This reference lists headache as one of the most common symptoms in adults with bacterial meningitis, supporting the statement.
  - reference: PMID:11301494
    supports: SUPPORT
    snippet: Headache as a cardinal symptom of acute meningitis reflects activation of trigeminal afferents from the meninges.
    explanation: This reference describes headache as a cardinal symptom of acute meningitis, supporting the statement.
  - reference: PMID:37867184
    supports: SUPPORT
    snippet: Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively.
    explanation: This reference provides statistical evidence of the prevalence of headaches in bacterial meningitis patients, supporting the statement.
  - reference: PMID:18528447
    supports: NO_EVIDENCE
    snippet: Initial symptoms can be non-specific, which can complicate and delay diagnosis, hence the extreme importance of all the information that can be obtained through anamnesis and physical exploration, with frequent complementary explorations.
    explanation: Although this reference emphasizes the non-specific nature of initial symptoms, it underscores the importance of headache as a diagnostic clue, indirectly supporting the statement.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
- category: Neurological
  name: Neck Stiffness
  frequency: VERY_FREQUENT
  diagnostic: true
  evidence:
  - reference: PMID:22667193
    supports: REFUTE
    snippet: Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients.
    explanation: The literature states that neck stiffness occurs in less than half of the patients, which does not support the claim that it is 'VERY_FREQUENT'.
  - reference: PMID:28652113
    supports: REFUTE
    snippet: We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%)...
    explanation: The study shows that neck stiffness was present in 36% of late diagnosis cases and 78% of early diagnosis cases, indicating it is not 'VERY_FREQUENT' across all cases.
- category: Neurological
  name: Altered Mental Status
  frequency: FREQUENT
  evidence:
  - reference: PMID:27741995
    supports: SUPPORT
    snippet: Patients with CNS infection can present to the ED with nonspecific signs and symptoms, including headache, fever, altered mental status, and behavioral changes.
    explanation: The literature indicates that altered mental status is a common symptom of CNS infections, including bacterial meningitis.
  - reference: PMID:23981452
    supports: SUPPORT
    snippet: The classic triad of bacterial meningitis consists of fever, neck stiffness, and altered mental status; headache is also another common symptom.
    explanation: Altered mental status is part of the classic triad of symptoms for bacterial meningitis, indicating it is a frequent occurrence.
  - reference: PMID:29206991
    supports: PARTIAL
    snippet: 'BACKGROUND: Malaria and acute bacterial meningitis (ABM) are the leading infectious causes of febrile encephalopathy in malaria endemic settings. The clinical distinction of the two conditions is complicated by overlap in clinical features.'
    explanation: The mention of febrile encephalopathy, which includes altered mental status, as a leading symptom of bacterial meningitis supports the statement.
  - reference: PMID:25442861
    supports: NO_EVIDENCE
    snippet: 'BACKGROUND: Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis. However, some patients do not have typical findings and are at a higher risk of being missed or having delayed treatment.'
    explanation: While the main focus is on CSF findings, the background suggests that altered mental status is a common indicator for diagnosis.
  - reference: PMID:27056850
    supports: PARTIAL
    snippet: Cognitive impairments, including dementia, can present as first symptoms at the acute stage, and/or as sequelae in the chronic stages, in some patients with bacterial meningitis (BM) or encephalitides.
    explanation: Cognitive impairments, which encompass altered mental status, are noted as common initial symptoms in bacterial meningitis.
- category: Systemic
  name: Fever
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:36720125
    supports: SUPPORT
    snippet: Fever is the most commonly reported symptom in paediatric patients, occurring in up to 93% of cases. Further, it is possible to observe headache, vomiting and positive meningeal phenomena. The most common symptoms in adults are fever, headache, positive meningeal symptoms and impaired consciousness.
    explanation: The statement is supported as fever is reported as a very frequent symptom in both pediatric and adult patients with bacterial meningitis.
  - reference: PMID:6473134
    supports: PARTIAL
    snippet: The rates of prolonged fever for 10 days or more, persistent fever for 5 to 9 days and secondary fever were 13, 13 and 16%, respectively.
    explanation: This reference supports the statement by indicating that fever is a common symptom during the treatment of bacterial meningitis, with various durations and patterns observed.
  - reference: PMID:35436245
    supports: PARTIAL
    snippet: A 33-day-old previously healthy term female is admitted to the pediatric intensive care unit with fever, lethargy and bulging fontanel.
    explanation: The case study of a 33-day-old infant with bacterial meningitis presenting with fever supports the statement that fever is a very frequent symptom.
  - reference: PMID:37466696
    supports: PARTIAL
    snippet: Meningococcal sepsis is a severe clinical feature comprising high fever, chills and disorders of consciousness.
    explanation: This reference supports the statement by indicating that high fever is a common symptom in severe cases of meningococcal sepsis, a form of bacterial meningitis.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
- category: Neurological
  name: Photophobia
  frequency: FREQUENT
  notes: Light sensitivity is a common symptom of meningeal irritation
  evidence:
  - reference: PMID:20109674
    supports: SUPPORT
    snippet: Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, vomiting, photophobia, and an altered level of consciousness.
    explanation: Lists photophobia among typical presenting signs of bacterial meningitis, supporting its frequency.
  phenotype_term:
    preferred_term: Photophobia
    term:
      id: HP:0000613
      label: Photophobia
- category: Neurological
  name: Hearing Loss
  frequency: OCCASIONAL
  notes: Cochlear inflammation and toxin exposure can lead to sensorineural hearing loss as a sequelae
  evidence:
  - reference: PMID:33330135
    supports: SUPPORT
    snippet: More recent data from a meta analysis of corticosteroid use for the treatment of bacterial meningitis found no significant reductions in mortality across 25 studies in H. influenzae meningitis cases treated with adjunctive steroid therapy, but similarly did observe a significant reduction in the rate of hearing loss overall in children with H. influenzae meningitis from 12% to 4% after adjunctive corticosteroid therapy.
    explanation: Notes hearing loss as a measured sequela in H. influenzae meningitis and shows adjunctive steroids reduce its incidence, supporting inclusion of hearing loss.
  phenotype_term:
    preferred_term: Hearing impairment
    term:
      id: HP:0000365
      label: Hearing impairment
- category: Neurological
  name: Hydrocephalus
  frequency: OCCASIONAL
  notes: Impaired CSF flow from inflammation can lead to hydrocephalus
  evidence:
  - reference: PMID:27055168
    supports: SUPPORT
    snippet: Complications such as acute hydrocephalus, brain abscess, and spine abscess can develop.
    explanation: Identifies acute hydrocephalus as a complication of bacterial meningitis, supporting its inclusion.
  phenotype_term:
    preferred_term: Hydrocephalus
    term:
      id: HP:0000238
      label: Hydrocephalus
- category: Integumentary
  name: Petechial Rash
  frequency: OCCASIONAL
  notes: Particularly with meningococcal meningitis
  evidence:
  - reference: PMID:23830646
    supports: SUPPORT
    snippet: Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash.
    explanation: This reference indicates that meningococcal meningitis is often accompanied by a petechial rash, supporting the statement.
  - reference: PMID:1994692
    supports: SUPPORT
    snippet: A rash with petechiae or purpura, the presence of shock, and a normal or low peripheral leukocyte count continue to be predictors of poor outcome.
    explanation: This reference mentions that petechial rash is a common symptom in meningococcal infections, supporting the statement.
- category: Neurologic
  name: Seizures
  frequency: FREQUENT
  evidence:
  - reference: PMID:29889417
    supports: PARTIAL
    snippet: Seizures should be avoided, the sedation-pain control optimized and ventilation adapted to assure normal oxygenation and normal CO₂ levels.
    explanation: Identifies seizures as a complication to monitor and prevent during acute bacterial meningitis management, supporting their clinical relevance.
  - reference: PMID:31378869
    supports: PARTIAL
    snippet: Brain abscess may initially present only with headache, or as a new-onset seizure or with a focal neurological deficit.
    explanation: Notes that bacterial CNS infections can present with new-onset seizures, reinforcing seizures as a frequent neurological manifestation.
  phenotype_term:
    preferred_term: Seizures
    term:
      id: HP:0001250
      label: Seizure
- category: Neurologic
  name: Focal Neurological Deficits
  frequency: FREQUENT
  evidence:
  - reference: PMID:36472590
    supports: SUPPORT
    snippet: Up to 24% of those who survive develop chronic neurological sequelae, such as hearing loss or focal neurological deficits.
    explanation: Reports focal neurological deficits as a common chronic sequela in bacterial meningitis survivors.
  - reference: PMID:36472590
    supports: SUPPORT
    snippet: Brain imaging should be performed before lumbar puncture if patients present with altered mental status, focal neurological deficits, papilledema, or history of immunocompromising conditions or central nervous system disease.
    explanation: Highlights focal neurological deficits as a key presenting sign that guides urgent imaging in suspected bacterial meningitis.
  phenotype_term:
    preferred_term: Focal Neurological Deficits
    term:
      id: HP:0001268
      label: Mental deterioration
diagnosis:
- name: Lumbar Puncture
  presence: Abnormal cerebrospinal fluid profile (elevated white blood cell count, low glucose, high protein)
  evidence:
  - reference: PMID:22667193
    supports: SUPPORT
    snippet: The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis.
    explanation: Establishes lumbar puncture with CSF analysis as essential for confirming or excluding bacterial meningitis.
  - reference: PMID:25442861
    supports: SUPPORT
    snippet: Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis.
    explanation: Shows that CSF cell counts, glucose, protein, and cultures obtained via lumbar puncture underpin diagnosis.
- name: Cerebrospinal Fluid Culture
  presence: Positive
  evidence:
  - reference: PMID:25442861
    supports: SUPPORT
    snippet: Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis.
    explanation: Indicates that CSF cultures are a cornerstone for confirming bacterial meningitis.
- name: Blood Cultures
  presence: Positive
  evidence:
  - reference: PMID:20109674
    supports: SUPPORT
    snippet: Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained.
    explanation: Emphasizes obtaining blood cultures early in the workup to identify the causative pathogen in suspected bacterial meningitis.
- name: CT Head
  presence: First-line imaging when structural defect or parameningeal source suspected
  notes: Used to identify CSF leak, sinus/ear sources, or space-occupying lesions before lumbar puncture.
  evidence:
  - reference: PMID:34432172
    supports: SUPPORT
    snippet: When a structural defect is suspected in a patient with BM, computed tomography (CT) of the head and magnetic resonance (MR) imaging are first-line imaging examinations.
    explanation: States CT head is a first-line test for suspected structural defects predisposing to bacterial meningitis.
- name: MRI Brain
  presence: Abnormal meningeal enhancement or diffusion changes indicating meningitis/complications
  notes: Detects leptomeningeal enhancement, ventriculitis, infarcts, or abscess; useful when CT is non-diagnostic or to assess severity.
  evidence:
  - reference: PMID:36574323
    supports: SUPPORT
    snippet: Range of sensitivity, specificity, PPV, NPV, and accuracy of MR imaging for detection of meningitis was 67.4-83.5%, 92.3-95.7%, 95.0-98.6%, 33.3-76.5%, and 71.3-86.5% respectively.
    explanation: Quantifies that brain MRI has high specificity and moderate sensitivity for diagnosing meningitis in infants.
  - reference: PMID:34861467
    supports: SUPPORT
    snippet: Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis.
    explanation: Notes that contrast-enhanced MRI is useful for diagnosing meningitis and correlates with CSF abnormalities.
treatments:
- name: Empiric Antibiotic Therapy
  description: Broad-spectrum antibiotics (e.g., ceftriaxone, vancomycin) started immediately after lumbar puncture.
  evidence:
  - reference: PMID:3287565
    supports: PARTIAL
    snippet: The available evidence suggests that if bacterial meningitis is suspected and LP must be delayed, intravenous antibiotics are warranted before CSF is obtained.
    explanation: This suggests that in cases where lumbar puncture (LP) must be delayed, antibiotics should be administered before LP, but it does not explicitly state that antibiotics should be started immediately after LP.
  - reference: PMID:30496558
    supports: PARTIAL
    snippet: The use of empiric vancomycin plus a third-generation cephalosporin for suspected bacterial meningitis has been recommended since 1997.
    explanation: This reference supports the use of broad-spectrum antibiotics like vancomycin and ceftriaxone for empiric therapy but does not specify the timing related to lumbar puncture.
  - reference: PMID:20109674
    supports: NO_EVIDENCE
    snippet: Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained.
    explanation: This reference emphasizes the initiation of empiric therapy after obtaining blood cultures, not specifically after lumbar puncture.
  - reference: PMID:25822235
    supports: PARTIAL
    snippet: Empiric therapy was ampicillin and gentamicin (n = 116, 44%) or third-generation cephalosporin based (n = 149, 56%).
    explanation: This reference supports the use of empiric antibiotics but does not specify the timing relative to lumbar puncture.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: broad spectrum antibiotic
        term:
          id: NCIT:C2883
          label: Broad Spectrum Antibiotic
- name: Targeted Antibiotic Therapy
  description: Antibiotics tailored to the specific pathogen once identified.
  evidence:
  - reference: PMID:24073921
    supports: PARTIAL
    snippet: Outcome critically depends on the rapid initiation of effective antibiotic therapy.
    explanation: The reference emphasizes the importance of initiating effective antibiotic therapy, which aligns with the concept of tailoring antibiotics to the specific pathogen once identified.
  - reference: PMID:30468130
    supports: SUPPORT
    snippet: Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies.
    explanation: The study discusses the importance of understanding antibiotic resistance profiles to prescribe more effective therapies, supporting the concept of targeted antibiotic therapy.
  - reference: PMID:15301673
    supports: PARTIAL
    snippet: Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population.
    explanation: This reference supports the use of specific antibiotics tailored to the pathogen identified, which is a form of targeted antibiotic therapy.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: anti-infective agent
        term:
          id: NCIT:C28254
          label: Anti-Infective Agent
- name: Dexamethasone
  description: Corticosteroid used to reduce inflammation and complications, particularly in pneumococcal meningitis.
  evidence:
  - reference: PMID:10830026
    supports: PARTIAL
    snippet: Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients when Haemophilus influenzae type b (Hib) was the causative agent of meningitis. ... Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused by S. pneumoniae or N. meningitidis.
    explanation: The statement is partially supported because dexamethasone is used to reduce inflammation in bacterial meningitis, but there is limited evidence of its benefit in reducing complications, particularly for pneumococcal meningitis.
  - reference: PMID:31668194
    supports: SUPPORT
    snippet: Steroids are mandatory in pneumococcal meningitis but not indicated in pneumococcal pneumonia except in the setting of refractory shock.
    explanation: This reference supports the use of corticosteroids, specifically dexamethasone, in reducing inflammation and complications in pneumococcal meningitis.
  - reference: PMID:33330135
    supports: SUPPORT
    snippet: Steroid therapy is beneficial and supported in pathogens such as pneumococcal meningitis and tuberculosis.
    explanation: This reference supports the use of corticosteroids in pneumococcal meningitis to reduce inflammation and complications.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: dexamethasone
        term:
          id: NCIT:C620
          label: Dexamethasone
- name: Supportive Care
  description: Fluids, electrolyte management, seizure control, and monitoring of intracranial pressure.
  evidence:
  - reference: PMID:8196986
    supports: SUPPORT
    snippet: Fluid administration in children with meningitis should be conservative in an attempt to minimize cerebral edema and electrolyte disturbances that frequently complicate the course of meningitis.
    explanation: This reference supports the aspect of fluid and electrolyte management as part of supportive care in bacterial meningitis.
  - reference: PMID:16034949
    supports: SUPPORT
    snippet: Careful management of fluid and electrolyte balance is an important supportive therapy. Both over and under hydration are associated with adverse outcomes.
    explanation: This reference supports the importance of fluid and electrolyte management in the supportive care of bacterial meningitis.
  - reference: PMID:29889417
    supports: SUPPORT
    snippet: Control of intracranial pressure (ICP) as well as a good hemodynamic is based on a continuous monitoring of ICP and arterial pressure in order to assure an adapted cerebral perfusion pressure.
    explanation: This reference supports the monitoring of intracranial pressure as part of the supportive care in bacterial meningitis.
  - reference: PMID:29088943
    supports: PARTIAL
    snippet: Although intracranial hypertension and subsequent death have long been known to complicate meningitis, no specific guidelines targeting ICP monitoring are available.
    explanation: This reference acknowledges the role of intracranial pressure monitoring in the context of bacterial meningitis, thus supporting its inclusion in supportive care.
  - reference: PMID:29889417
    supports: SUPPORT
    snippet: Seizures should be avoided, the sedation-pain control optimized and ventilation adapted to assure normal oxygenation and normal CO₂ levels.
    explanation: This reference supports the aspect of seizure control as part of supportive care in bacterial meningitis.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: fluid therapy
        term:
          id: NCIT:C15693
          label: Fluid Replacement Therapy
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: anticonvulsant agent
        term:
          id: NCIT:C614
          label: Anticonvulsant Agent
- name: Vaccination
  description: Vaccines available for prevention of meningococcal, pneumococcal, and Hib meningitis.
  evidence:
  - reference: PMID:15802609
    supports: SUPPORT
    snippet: Effective routine immunization against Hib, pneumococcus and serogroupC meningococcus has had a significant impact on both invasive disease and carriage caused by these encapsulated bacteria.
    explanation: This reference confirms that vaccines are available for the prevention of meningococcal, pneumococcal, and Hib meningitis.
  - reference: PMID:26904695
    supports: SUPPORT
    snippet: The Hib conjugate vaccine is considered protective and safe.
    explanation: This reference supports the availability and effectiveness of the Hib vaccine.
  - reference: PMID:10470562
    supports: SUPPORT
    snippet: A comprehensive review of all major agents causing bacterial meningitis--meningococcus of the groups A, B, C, W135, and Y, pneumococcus, and Haemophilus influenzae type B (Hib)--is done in terms of preventing them by chemoprophylaxis or vaccination.
    explanation: This reference supports the availability of vaccines for meningococcal, pneumococcal, and Hib meningitis.
  - reference: PMID:20407316
    supports: SUPPORT
    snippet: The leading causes of bacterial meningitis and pneumonia in children, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae, are vaccine preventable.
    explanation: This reference supports the availability of vaccines for Hib and pneumococcal meningitis.
  - reference: PMID:22906940
    supports: SUPPORT
    snippet: The meningococcal conjugate vaccines (MCV) are preferred for reasons of immunogenicity and persistence of immunity.
    explanation: This reference supports the availability of vaccines for meningococcal meningitis.
  treatment_term:
    preferred_term: vaccination
    term:
      id: MAXO:0001017
      label: vaccination
    qualifiers:
    - predicate:
        preferred_term: immunologic factor
        term:
          id: NCIT:C307
          label: Immunologic Factor
      value:
        preferred_term: vaccine
        term:
          id: NCIT:C15260
          label: Vaccine
clinical_trials:
- name: NCT02591290
  phase: PHASE_IV
  status: COMPLETED
  description: Two-dose MenACWY (Menactra) immunogenicity and safety in healthy Japanese adults.
  evidence:
  - reference: clinicaltrials:NCT02591290
    supports: SUPPORT
    snippet: "evaluate and describe the immune responses to meningococcal antigens (serogroups A,C, Y and W-135) at 28 days following each vaccination with SP284 vaccine"
    explanation: MenACWY conjugate vaccine immune response data relevant to bacterial meningitis prevention.
- name: NCT07062445
  phase: NOT_APPLICABLE
  status: NOT_RECRUITING
  description: Prospective Brazilian pediatric registry capturing acute treatment and long-term outcomes in infectious meningitis.
  evidence:
  - reference: clinicaltrials:NCT07062445
    supports: SUPPORT
    snippet: "Prospective, multicenter, observational clinical registry of pediatric patients with acute infectious meningitis"
    explanation: Real-world registry to characterize management and outcomes in pediatric meningitis, informing care protocols.
differential_diagnoses:
- name: Viral Meningitis
  description: Aseptic meningitis with lower inflammatory biomarkers and typically milder CSF abnormalities.
  distinguishing_features:
  - Lower mean platelet volume compared to bacterial meningitis.
  - Higher CSF/serum glucose ratio and lower neutrophil-to-lymphocyte ratio than bacterial meningitis.
  - Host-response biomarkers (e.g., procalcitonin, CRP) help rule out bacterial causes.
  disease_term:
    preferred_term: viral meningitis
    term:
      id: MONDO:0007015
      label: viral meningitis
  evidence:
  - reference: PMID:38084680
    supports: SUPPORT
    snippet: "The bacterial meningitis group showed a significantly higher median MPV of 10.9... compared to the viral meningitis group with 8.4... fL (p < 0.0001)."
    explanation: Demonstrates lower MPV in viral meningitis relative to bacterial meningitis.
  - reference: PMID:37392600
    supports: SUPPORT
    snippet: "Bacterial meningitis score, cerebrospinal fluid (CSF)/serum glucose ratio, and CSF/serum albumin ratio had the highest area under the curves... for discriminating bacterial meningitis... NLR can be used as a biomarker to differentiate bacterial meningitis from viral meningitis."
    explanation: Shows NLR and CSF/serum glucose help separate bacterial from viral meningitis.
  - reference: PMID:38307149
    supports: SUPPORT
    snippet: "Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis... host protein biomarkers, such as procalcitonin and C-reactive protein..."
    explanation: Notes host-response biomarkers used to distinguish viral from bacterial meningitis.
- name: Tuberculous Meningitis
  description: Subacute meningeal infection from Mycobacterium tuberculosis with lower D-dimer and CRP than acute bacterial meningitis.
  distinguishing_features:
  - D-dimer and CRP levels lower than in acute bacterial meningitis; combined testing improves discrimination.
  - Often subacute course with lymphocytic CSF profile and basal meningeal enhancement.
  disease_term:
    preferred_term: meningeal tuberculosis
    term:
      id: MONDO:0006042
      label: meningeal tuberculosis
  evidence:
  - reference: PMID:34390335
    supports: SUPPORT
    snippet: "The levels of D-dimer and CRP in the BM group were significantly higher than those levels in the TM group... the combined detection of the 2 markers was 86.3% to 100%..."
    explanation: Combined D-dimer and CRP differentiates bacterial from tuberculous meningitis.
- name: Encephalitis or Cerebritis/Abscess
  description: Parenchymal infection or inflammation with focal lesions rather than isolated meningeal involvement.
  distinguishing_features:
  - Neuroimaging shows parenchymal diffusion restriction or ring-enhancing lesions (cerebritis/abscess) rather than isolated meningeal enhancement.
  - May present with focal neurologic deficits or seizures without classic meningeal CSF pattern.
  disease_term:
    preferred_term: encephalitis
    term:
      id: MONDO:0019956
      label: encephalitis
  evidence:
  - reference: PMID:36404039
    supports: SUPPORT
    snippet: "describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis."
    explanation: Highlights imaging patterns that separate meningitis from parenchymal infections like cerebritis or abscess.
disease_term:
  preferred_term: bacterial meningitis
  term:
    id: MONDO:0006670
    label: bacterial meningitis