Acute Bacterial Meningitis (ABM)

• Acute Bacterial Meningitis (ABM) involves symptoms lasting less than 5 days.
• ABM accounts for 75% of community-acquired meningitis cases.
• ABM is commonly caused by unknown, viral, and bacterial pathogens.
• Subacute meningitis lasts 5+ days and is associated with comorbidities, immunosuppression, and fungal etiologies.
• Chronic meningitis lasts >4 weeks.
• Encephalitis presents with fever, new-onset seizure, focal neurologic findings, personality changes, cognitive impairment, CSF pleocytosis, and abnormal MRI or EEG findings.

CNS Anatomy and CSF Flow

• CSF production occurs in the choroid plexus of the 3rd ventricle.
• CSF flows through the cerebral aqueduct (of Sylvius).
• CSF is reabsorbed through arachnoid granulations.

Epidemiology of Acute Bacterial Meningitis

• A decreased incidence of acute bacterial meningitis is noted.
• Haemophilus influenzae type b (Hib) meningitis has largely disappeared.
• Altered age distribution, with a mean age from 30 to 41 years.
• Case fatality rates have remained relatively stable from 1999 (15.7%) to 2007(14.3%)
• Decreased incidence is due to effective vaccination.

Etiologic Agents of ABM

• Streptococcus pneumoniae accounts for 47% of cases with a 21% fatality rate.
• Neisseria meningitidis accounts for 25% of cases with a 3% fatality rate.
• Group B Streptococcus (GBS) accounts for 12% of cases with a 7% fatality rate.
• Listeria accounts for 8% of cases with a 15% fatality rate.

Relationship Between Bacterial Pathogens and Risk Factors

• Age <1 month: Streptococcus agalactiae, Escherichia coli, and Listeria monocytogenes.
• Age 1-23 months: S. agalactiae, E. coli, Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis.
• Age 2-50 years: S. pneumoniae and N. meningitidis.
• Age >50 years: S. pneumoniae, N. meningitidis, L. monocytogenes, and aerobic gram-negative bacilli.
• Immunocompromised state: S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli (including Pseudomonas aeruginosa).
• Basilar skull fracture: S. pneumoniae, H. influenzae, and group A streptococci.
• Head trauma/neurosurgery: Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including P. aeruginosa).

Pathogenesis

• Nasopharyngeal colonization leads to local invasion and bacteremia.
• This progresses to meningeal invasion and bacterial replication in the subarachnoid space.
• Release of bacterial components (cell wall, LOS) causes cerebral microvascular endothelium activation.
• Macrophages, neutrophils, and other CNS cells releases cytokines which causes subarachnoid space inflammation and cerebral vasculitis.
• Increased BBB permeability leads to vasogenic edema.
• Hydrocephalus leads to interstitial edema.
• Cytotoxic edema results in increased intracranial pressure.
• Decreased cerebral blood flow and loss of cerebrovascular autoregulation can cause cerebral infarction.

Predisposing Factors for Bacterial Meningitis

• Acute and chronic otitis media
• Sinusitis
• Pneumonia
• Endocarditis
• Recent or remote head injury
• Altered immune system
• Alcoholism
• Diabetes
• CSF leak
• Cochlear implants
• No predisposing factor in 20% of cases.

Skull Fracture

• Can cause raccoon eyes
• Associated with Streptococcus pneumoniae, H. influenzae, or Streptococcus Group A

Mastoiditis

• Associated with chronic otitis media
• The petrosal bone contains the facial canal, this is where the facial nerve crosses.

Streptococcus pneumoniae

• This isthe most common etiology of bacterial meningitis in the USA
• Causes 58% of cases in persons > 19 years old.
• Serotype replacement can occur and is vaccine preventable with PCV10 and PCV13
• Suppurative foci can include Pneumonia (25%), OM/ Mastoiditis (30%), and Sinusitis (10-15%)
• Can result in endocarditis
• Head trauma with CSF leak is most common cause
• Pneumococcal conjugate vaccine is effective in decreasing incidence.

Haemophilus influenzae Type B

• Causes 3-7% of meningitis cases, with mortality rate is 3-6%.
• Capsular type b strains were > 90% of serious infections
• Concurrent pharyngitis or OM in > 50% of cases.
• Peak incidence at 6-12 months.
• Risk factors in persons > 6 years: Sinusitis/OM, Epiglottitis, DM, CSF Leak, Pneumonia, Splenectomy, Immune deficiency, Alcoholism

Neisseria meningitidis

• Causes outbreaks of meningitis within close-knit groups, S. pneumoniae and H. influenzae do not.
• N. meningitidis affects mostly children and young adults with mortality rate 3-13%
• Most endemic disease in USA with Serogroups: B, C, Y.
• Can have epidemics by serogroups A and C
• Serogroup Y is associated with pneumonia
• Serogroup C disease is on the rise in the USA
• Acquired through nasopharyngeal route via respiratory droplets.
• N. meningitidis is considered normal flora of nose.

Underlying Immune Defects as Risk Factors

• Deficiencies in the terminal complement components (C5, C6, C7, C8, and perhaps C9):MAC
• Dutch family with dysfunctional properdin
• MSM :RR 4, if HIV + RR 10, MSM means men having sex with men.
• Eculizumab & Ravulizumab (1000- to 2000-fold increased risk).

Population Risk Factors for Meningococcal Disease

• Household exposure
• Demographic and socio-economic factors and crowding
• Concurrent upper respiratory tract infections
• Active and passive smoking

Geographical Distribution of Serogroups

• The U.S. and Europe, the rate is 1-3/100,000
• Sub-Saharan Africa, the rate is 10-25/100,000.
• In the Americas, Serogoups include B, C, and Y.
• In Africa, Serogroups include A, B, and C.
• In Asia, Serogroups include A and C.
• In Europe, serogroups include B and C

Meningitis Belt

• A range of countries in Sub-Saharan Africa from Senegal to Ethiopia.
• From December to April (dry season) which runs from December to April.
• Increased incidence of meningitis due to Saharan Dust.
• Most meningitis cases were caused by N. meningitis.

Listeria monocytogenes

• Accounts for 2-8% of all meningitis cases
• High mortality rate is 20-30%
• Isolated from dust, soil, sewage, milk, cheese, decaying vegetables
• Predisposing factors includes exposure among neonates, alcoholics, cancer, transplant recipients, DM, RF, CLD, CVD, iron overload, pregnant women, TNF-alpha inhibitor use, and those using corticosteroids.
• Infections can cause Rhombencepahlitis presents with Ataxia, and Nystagmus
• More likely to affect the elderly

Streptococcus agalactiae (GBS)

• Can affect neonates, and occasionally adults > 60 years
• Early onset associated with prematurity, PROM, and low birth weight
• Vertical transmission from colonized vaginal and rectal areas
• Risk factors: OM, > 60 years, CVD, cardiac disease, alcoholism, renal failure, hepatic failure, corticosteroids, and DM

Staphylococci spp

• S. aureus is associated with post neurosurgery, post trauma, CSF shunt, IVDU, malignancies, DM, and alcoholism. The bacteria is most common among patients with catheters and prosthetic limbs
• Healthcare-associated ventriculitis and meningitis is known as hospital-acquired
• If underlying IE, can cause a paraspinal infection with Epidural and Paraspinal abscesses
• S. epidermidis the most common agent of CSF shunt infection
• Has high mortality rate.

Gram-Negative Bacilli

• Common bacteria includes E.coli (K1 capsular polysaccharide), K.pneumoniae, Pseudomonas spp., Salmonella spp., Acinetobacter spp.
• Bacteria such as Citrobacter diversus is seen in newborns
• Increased mortality rates occurs with 2/3 developing brain abscess
• Head trauma patients, and those undergoing neurosurgery can develop hospital acquired Gram-Negative Bacilli infection
• Disseminated strongyloidiasis (hyperinfection) is related to Immunocompromised patients

Signs and Symptoms of ABM

• The triad associated with ABM include Headache, Fever, Meningismus
• Commonly causes Altered sensorium
• Vomiting, Seizures, Focal neurologic findings, and Papilledema are also common

Kernig's and Brudzinski's Sign

• These signs are used to assess the central nervous system.

Typical CSF Findings in Bacterial Meningitis

• Opening pressure: ≥ 180 mm H₂O
• WBC count: 1,000-5,000 mm3, with > 80% neutrophils
• Protein: >100 mg/dl
• Glucose: < 40 mg/dl
• Lactate: >35 mg/dl
• GS: Positive 60-90 %
• Culture: Positive 70-85 %
• Limulus lysate: Positive in GNR
• Latex agglutination: Sensitivity 50- 100%
• PCR: Excellent Sensitivity/specificity

Typical Cerebrospinal Fluid Findings in Patients with Meningitis

• Viral Meningitis: White blood cell count of 50-1000 (Cell/mm3), with Mononuclear cells >45 (mg/dl), with Protein <200 (mg/dl)
• Bacterial Meningitis: White blood cell count of 1000-5000 (Cell/mm3), with Neutrophilic cells <40 (mg/dl), with Protein 100-500 (mg/dl)
• Tuberculous Meningitis: White blood cell count of 50-300 (Cell/mm3), with Mononuclear cells <45 (mg/dl), with Protein 50-300 (mg/dl)
• Cryptococcal Meningitis: White blood cell count of 20-500 (Cell/mm3), with Mononuclear cells <40 (mg/dl), with Protein >45(mg/dl)

IDSA Guidelines for Bacterial Meningitis

• If suspicion for bacterial meningitis and positive risk factors administer Dexamethasone+ and empirical antimicrobial therapy immediately
• If suspicion is high for bacterial meningitis and there are no risk factors administer Dexamethasone+ and empirical antimicrobial therapy

Therapy for Meningitis

• Goal is good CSF penetration; depends on BBB which relies on low molecular weight, high lipid solubility, in addition to low protein binding, and low ionization at physiological pH
• Needed is Bactericidal effect: for rapid CSF sterilization
• Add Corticosteroids: change in perspective

IDSA Guidelines for Empiric Antimicrobial Therapy of Purulent Meningitis

• Preterm - < 1 month: administer AMP + cefotaxime or administer AMP + genta
• 1 month - 50 years: Cefotaxime 2g IV q 4-6 h, OR Ceftriaxone 2 g IV q 12h + dexamethasone + Vanco
• > 50 years: AMP 2 g IV q 4 h+ ceftriaxone OR cefotaxime + Vanco + dexa or MER 2 g IV q 8 h + Vanco + dexa
• Note, administer steroids before ABx or concomitantly, and care will need to be exercised in using vancomycin plus dexamethasone for possible PRSP since vancomycin levels may be reduced with a decrease in inflammation.

Suggested Duration of Therapy

• S.pneumoniae: 10-14 days
• H.influenza: 7 days
• N.meningitidis: 7 days
• GBS/S. agalactiae: 21 days
• GNR: 10-14 days
• Listeria monocytogenes: 14-21 days

Prevention

• Administer Meningococcal Vaccine for Recommended high risk groups
• Give Chemoprophylaxis
• Administer Hib Vaccine

N.meningitidis Chemoprophylaxis

• Chemoprophylaxis is key for Close contacts: which include Household members (300-1000 risk), Daycare centers classmates and teachers, and Anyone directly exposed to oral secretions.
• Treat as soon as possible
• RIF 600 mg po q 12 X 4 doses, Cipro 500 mg po (single dose), or Ceftriaxone 250 mg IM X 1 dose are used
• Secondary cases are rare in industrialized countries

Neurologic Complications of Meningitis

• Cerebral edema
• Increased ICP
• Seizures
• Cerebral infarction
• Hydrocephalus
• Subdural effusion
• Hyponatremia
• Sensorineural hearing loss

Long-Term Sequelae

• Cognitive deficit
• Bilateral hearing loss
• Motor deficit
• Seizures
• Visual impairment
• Hydrocephalus
• Behavioral or intellectual disorders

Brain Abscess

• Focal, intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus by a wellvascularized capsule

Predisposing Conditions for Brain Abscess

• Adjacent focus of infection accounts for 30-50% of brain abscesses including OM, Mastoiditis, Sinusitis, Face/ scalp infections,Dental sepsis, Penetrating head injury, and Post-surgical

Hematogenous Spread

• Hematogenous spread causes 35% of abscesses
• Caused by Lung abscess, Congenital heart disease, and Bacterial IE
• 20 % are Cryptogenic

Microbiologic Etiology of Brain Abscess

• 23-33% associated with Enterobacteriacea
• 60-70% associated with S.milleri spp
• 20-40% associated with Bacteroides spp
• Less than 1% is associated with both S.pneumonia and H.influenza

Causes fo Eosiniphilic meningitis

• can be caused by parasites such as Angiostorngylus cantonensis, Gnasthostoma spinigerum, Bayliscaris procyonis, Taenia solium
• And other infections such as LCM virus, M. tuberculosis, T.pallidum, Rickettsia  rickettsi, C. immitis, and other fungi