Acute Bacterial Meningitis (ABM)

Acute Bacterial Meningitis (ABM)

• ABM involves symptoms lasting less than 5 days.
• ABM accounts for 75% of community-acquired meningitis cases.
• ABM is most commonly caused by unknown pathogens, including viral and bacterial organisms.
• Subacute meningitis lasts 5 days or more and is associated with comorbidities, immunosuppression, or fungal etiologies.
• Chronic meningitis lasts more than 4 weeks.
• Encephalitis: symptoms include fever, new-onset seizures, focal neurologic findings, personality changes, cognitive impairment, CSF pleocytosis, and abnormal MRI or EEG findings.

Epidemiology of Acute Bacterial Meningitis

• Incidence has decreased because of vaccination.
• Haemophilus influenzae (Hib) meningitis has disappeared due to vaccination.
• There has been an altered age distribution with the mean age increasing from 30 to 41 years.
• The case fatality rate has remained relatively unchanged.

Etiologic Agents of ABM

• Most Common Isolates:
  • H. influenza rate is 7%, with a 6% Fatality rate. -S. pneumonia rate is 47%, with a 21% Fatality rate. -N. meningitidis rate is 25%, with a 3% Fatality rate.
  • GBS rate is 12%, with a 7% Fatality rate.
  • Listeria rate is 8%, with a 15% Fatality rate.

Relationship Between Bacterial Pathogens and Predisposing Factors

• Age Specific pathogens: -In infants less than 1 month (Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes). -Between 1-23 months (S. agalactiae, E. coli, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis). -Between 2-50 years (S. pneumoniae, N. meningitidis). -In patients greater than 50 years (S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli)
• Immunocompromised/Basilar skull fracture/Head trauma; post neurosurgery: can lead to bacterial pathogens and factors predisposing to meningitis.

Predisposing Factors for Bacterial Meningitis

• Acute and chronic otitis media
• Sinusitis
• Pneumonia
• Endocarditis
• Head injury (recent or remote)
• Altered immune system
• Alcoholism
• Diabetes
• CSF leak
• Cochlear implants
• 20% have no predisposing factor

S. pneumoniae

• Most common bacterial meningitis etiology in the USA
• 58% of cases occur in people > 19 years
• Serotype replacement with PCV10 and PCV13
• Suppurative foci are Pneumonia (25%), OM/ Mastoiditis (30%), and Sinusitis (10-15%).
• IE (<5%)
• Head trauma CSF leak (10%)
• Pneumococcal conjugate vaccine may be effective in decreasing incidence

Haemophilus influenzae Type B

• Causes 3-7% of cases with a mortality rate of 3-6%.
• Capsular type b strains account for > 90% of serious infections.
• Concurrent pharyngitis or OM occurs in > 50% of cases.
• Peak incidence occurs at 6-12 months.
• Risk factors in persons > 6 years include sinusitis/OM, epiglottitis, pneumonia, splenectomy, immune deficiency, DM, and CSF leak.

N. meningitidis

• Causes outbreaks of meningitis within close-knit groups of people
• S. pneumonia and H. influenzae do NOT cause outbreaks.
• Underlying immune defects: -Deficiencies in terminal complement components (C5, C6, C7, C8, and perhaps C9): MAC. -Dutch family with dysfunctional properdin -Men who have sex with Men :RR 4, if HIV+ RR 10 -Eculizumab & Ravulizumab (1000- to 2000-fold increased risk)
• Population Risk Factors: Household exposure/ Demographic and socio-economic factors and crowding/ Concurrent upper respiratory tract infections/ Active and passive smoking
• Serogroup Y can be associated with Pneumonia.
• Serogroup C disease is increasing in the USA.

Meningococcal Meningitis

• Meningococcal Meningitis affects mostly children and young adults
• Mortality rate is 3-13%
• Most endemic disease in USA Serogroups: B,C,Y
• Can cause epidemics by serogroups A and C.
• Nasopharyngeal acquisition of infection, Normal flora of nose
• Respiratory droplet transmission

Listeria monocytogenes

• Accounts for 2-8% of meningitis cases and has a high mortality rate of 20-30%.
• Isolated from dust, soil, sewage, milk, cheese, and decaying vegetables.
• Predisposing factors: neonates, alcoholics, cancer, transplant recipients, DM, RF, CLD, CVD, iron overload, pregnant women, TNF-alpha inhibitor use, and corticosteroid use.
• Can cause Rhombencepahlitis with ataxia and nystagmus.
• Typically affects the elderly population.

Streptococcus agalactiae (GBS)

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

Staphylococci spp

• S. aureus occurs after neurosurgery, with trauma, CSF shunt, IVDU, malignancies, DM, alcoholism, ESRD/HD . Patients with catheters and prosthetic limbs.
• Healthcare-associated ventriculitis and meningitis/Hospital-acquired
• Underlying IE, paraspinal infection. Epidural and Paraspinal abscesses present
• S. epidermidis: most common agent of CSF shunt infection
• High Mortality

Gram-Negative Bacilli

• Includes E. coli (K1 capsular polysaccharide), K. pneumoniae, Pseudomonas spp., Salmonella spp., Acinetobacter spp.
• Citrobacter diversus: common in newborns, with increased mortality rates, and 2/3 develop brain abscess.
• Risk factors include head trauma, neurosurgery, hospital acquired cases, and disseminated strongyloidiasis (hyperinfection) in immunocompromised patients.

ABM Symptoms and Signs

• The triad of ABM consists of headache, fever, and meningismus.
• Headache: Relative Frequency ≥85
• Fever: Relative Frequency ≥80
• Meningismus: Relative Frequency ≥80 (pain when you move "your neck")
• Altered sensorium: Relative Frequency ≥75
• Vomiting: Relative Frequency approximately 35
• Seizures: Relative Frequency approximately 30
• Focal neurologic findings: Relative Frequency 10-35
• Papilledema: Relative Frequency 5

CSF Findings in Bacterial Meningitis

• Opening pressure: ≥ 180 mm H₂O: Impaired CSF Flow
• WBC count: 1,000-5,000 mm3↑
• % Neutrophils: > 80% ↑
• Protein: >100 mg/dl ↑
• Glucose: < 40 mg/dl
• Lactate: >35 mg/dl↑
• GS: positive in 60-90%
• Culture: positive in 70-85%
• Limulus lysate*: positive in Gram-negative rods
• Latex agglutination: Sensitivity 50-100%
• PCR: Excellent sensitivity and specificity

Therapy for Bacterial Meningitis

• Therapy should include good CSF penetration.
  • This depends on Blood Brain Barrier
• Therapies should have a bactericidal effect for rapid CSF sterilization.
  • Drugs: Low MW, high lipid solubility, low protein binding, low ionization at physiological pH: All of these characteristics are to cross BBB.
• Corticosteroids can change the perspective in Meningitis therapies.

IDSA Guidelines for Empiric Antimicrobial Therapy of Purulent Meningitis

• Preterm- < 1 month:
  • AMP (ampicillin) + cefotaxime
• 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+ ceftraxione OR cefotaxime + Vanco + dexa Dexamethasone must be administered concurrently or 30min before antibiotics.
• AMP: ampicillin
• 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. Administer steroids before ABx or concomitantly

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

• Meningococcal Vaccine: Recommended high risk.
• groups like college freshmen living in dormitories, lab technician, travel to endemic areas, HIV, splenectomy, mAB, US military.
• Chemoprophylaxis
• Hib Vaccine

N. Meningitidis Chemoprophylaxis

• "Close contacts" (more than 3 hours at less than 3-6 ft of distance) include household members (300-1000 risk) /daycare centers classmates and teachers/ anyone directly exposed to oral secretions.
• Treatment as soon as possible utilizing RIF 600 mg po q 12 X 4 doses/Cipro 500 mg po (single dose)/Ceftriaxone 250 mg IM X 1 dose
• Secondary cases in industrialized countries are rare

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 begins as a localized area of cerebritis and develops into a collection of pus by a well-vascularized capsule.

Predisposing Conditions for Brain Abscess

• Adjacent focus of infection occurs in 30-50% of cases -OM -Mastoiditis -Sinusitis -Face/ scalp infections -Dental sepsis -Penetrating head injury -Post-surgical
• Hematogenous spread occurs in 35% -Lung abscess -Congenital heart disease -Bacterial IE
• Cryptogenic occurs in 20% of cases

Microbiologic Etiology of Brain Abscess

• S.aureus- 10-15%
• Enterobacteriacea- 23-33%
• S.pneumonia <1
• H.influenza <1
• S.milleri spp 60-70%
• Bacteroides spp 20-40%
• Fungi 10-15%
• Protozoa <1

Eosinophilic Meningitis

• Parasites: Angiostorngylus cantonensis, Gnasthostoma spinigerum, Bayliscaris procyonis, Taenia solium
• Other Infectious Causes: LCM virus, M. tuberculosis, T.pallidum, Rickettsia rickettsi, C. immitis, other fungi

Aseptic Meningitis

• Enteroviruses most common (Coxackievirus A6, EV D 68, EV 71)
• Arboviruses (Powassan, SLE, CE, WNVE, Lymphocytic choriomeningitis virus (LCMV)
• Mumps, HIV
• Japanese Encephalitis
• Dengue, CHICKV, ZikaV