DESCRIPTION

CNS infection with inflammation of leptomeninges defined by an increased number of WBCs in the CSF often associated with fever, nuchal rigidity, headache, and altered mental status.

ETIOLOGY

• Bacterial:
  • Neonates: Group B Streptococcus, Escherichia coli and other enteric bacilli, Listeria monocytogenes
  • Children/adults: Streptococcus pneumoniae, Neisseria meningitidis, group B Streptococcus and gram-negative bacilli (< 3 yr)
  • Elderly/alcoholic: S. pneumoniae, gram-negative bacilli, Listeria spp.
  • Neurosurgical patients: Staphylococcus and gram-negative organisms
  • Transplant recipients and dialysis patients: Increased incidence of Listeria spp. infection
  • AIDS: Above, plus tuberculosis, fungal, syphilis
• Viral
• Fungal
• Chemical, drug, or toxin induced

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• General:
  • Fever
  • Nuchal rigidity:
    • Kernig: Flexed knee resists extension (bilateral).
    • Brudzinski: Flexion of neck produces flexion at hips.
    • Kernig and Brudzinski signs are neither sensitive nor specific for meningitis.
  • Altered mental state, headache
  • Photophobia
  • Papilledema
  • Focal CNS abnormalities
  • Seizure, nonsimple
  • Petechial and palpable purpuric rash (meningococcal infection)
  • Associated infections: Sinusitis, otitis media, pneumonia
• Infant/pediatric:
  • Fever or hypothermia
  • Lethargy
  • Weak suck
  • Vomiting
  • Dehydration
  • Respiratory distress
  • Apnea
  • Cyanosis
  • Bulging fontanel
  • Hypotonia
  • Meningismus often absent in < 1 yr old
• Elderly and immune compromised:
  • Confusion with or without fever
  • Less-striking symptoms overall

History

• Neonates: Prematurity, intrapartum complications as fever, prolonged rupture of membrane, antibiotic use, group B Streptococcus infection
• Adults: Recent travels
• Elderly: Pneumococcal vaccination status
• Immunologic incompetency suggested by frequent infections
• Recent trauma or ENT, facial, or neurologic surgery
• Shunt

ESSENTIAL WORKUP

• Treat immediately based on clinical suspicion
• Blood cultures. Give antibiotic therapy if at all possible after blood cultures but before other diagnostic procedures if patient is unstable.
• Routine CT before lumbar puncture (LP) not always required. Generally indicated with:
  • Immune deficiency/HIV
  • History of CNS disease (abscess, bleed, mass lesion, stroke, shunt)
  • History of seizure < 7 days
  • Focal neurologic deficit
  • Altered level of consciousness
  • Age > 60 yr
  • Papilledema
• LP: Every suspected meningitis patient unless contraindicated:
  • May delay LP when:
    • Risk for herniation (see above)
    • Unstable patient
    • Thrombocytopenia or bleeding diathesis
    • Spinal epidural abscess
    • Overlying soft tissue infection
• CSF analysis:
  • Tube 1: Cell count and differential
  • Tube 2: Protein and glucose
  • Tube 3: Gram stain, culture, and sensitivity
• May add acid-fast bacillus smear, TB culture, India ink and fungal cultures, VDRL, cryptococcal antigen as needed
  • Tube 4: Repeat cell count or save for additional tests.
  • Check for elevated opening pressure: Normal up to 200 mm H₂O
  • Latex agglutination (optional):
    • Useful if other tests are not diagnostic
    • Best if urine and blood also tested
    • Detects: Meningococcus, Pneumococcus, group B Streptococcus, Haemophilus influenzae, E. coli, Cryptococcus
  • Polymerase chain reaction (optional):
    • Useful for virus (especially herpes simplex) and bacteria: N. meningitidis, S. pneumoniae, H. influenzae A and B
  • CSF interpretation:
    • Culture is diagnostic
    • > 4 WBC/mL in CSF is highly sensitive for meningitis for age > 3 mo and > 9 WBC/mL for infants 29–90 days.
    • Cell count may be normal in HIV/AIDS.
    • Neonate: Up to 20–25 WBC/mL and protein up to 150 mg/dL in term and up to 100 mg/dL in preterm neonate may be normal.
  • Typical bacterial meningitis:
    • CSF glucose < 40 mg/dL. Also ratio of CSF to blood glucose < 0.6.
    • WBC > 500/mL (usually 1,000–20,000). However, significantly fewer WBC count may be seen in the early course of the disease.
    • Differential > 80% polymorphonuclear neutrophils (PMNs) is suggestive.
    • CSF protein > 200 mg/dL. Normally < 50 mg/dL.

DIAGNOSIS TESTS & INTERPRETATION

Lab

• Blood cultures (2 sets) before antibiotics
• Urine culture and urinalysis
• CBC with differential and platelets
• Electrolytes/glucose:
  • Calculate CSF glucose to serum glucose ratio
  • Assess for metabolic acidosis, SIADH
  • BUN/creatinine for medication dosing
• Prothrombin time, partial thromboplastin time, and platelet: Particularly in patients with petechiae or purpura:
  • Obtain before LP in severe sepsis or disseminated intravascular coagulation
• Toxicology studies as needed

Imaging

• CT: See essential workup section above.
• CXR: Pneumonia, TB if suspected

DIFFERENTIAL DIAGNOSIS

• Encephalitis
• Brain, spinal, epidural abscess
• Febrile seizure
• CNS/systemic lupus erythematosus cerebritis
• Intracranial bleed
• Primary or metastatic CNS malignancy
• Stroke
• Venous sinus thrombophlebitis
• Trauma
• Toxic/metabolic

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

PRE-HOSPITAL

• IV, O₂, and transport. ABCs
• Administer prophylactic antibiotics to any close personal contacts of patient diagnosed with meningococcal meningitis:
  • Adults:
    • Rifampin: 600 mg PO BID for 2 days; or
    • Ciprofloxacin: 500 mg PO single dose; or
    • Ceftriaxone: 250 mg IM (if pregnant)
  • Children:
    • Rifampin: 5 mg/kg if < 1 mo old and 10 mg/kg if > 1 mo old, BID for 4 doses

INITIAL STABILIZATION/THERAPY

• Isolate patient as appropriate.
• ABCs. Treat seizures.

ED TREATMENT/PROCEDURES

• Ideally perform LP and give antibiotic ± steroids promptly.
• If LP is delayed, give antibiotic ± steroids empirically before LP.
• If CT is indicated prior to LP, empiric antibiotic ± steroids should be given prior to CT.
• Steroids: If given, should be given prior to, or concurrently with, administration of antibiotics.
• Antibiotics:
  • Obtain blood cultures before antibiotics.
  • Do not delay giving antibiotics to obtain LP or CT unless absolutely necessary.
• IV (or IM) empiric antibiotics for presumed bacterial Infection:
  • Neonates:
    • 0–7 days old: Ampicillin 50–100 mg/kg q6h + gentamicin 2.5 mg/kg q8–12h
    • > 7 days old: Ampicillin 50–100 mg/kg q6–8h; + cefotaxime 50 mg/kg q6h or gentamicin 2.5 mg/kg q8h
    • Add acyclovir 10–20 mg/kg q8h for suspected herpes simplex encephalitis.
  • Age 1–3 mo:
    • Ampicillin 50–100 mg/kg q6h; + ceftriaxone 75 mg/kg load, then 50 mg/kg q12h thereafter or cefotaxime 50 mg/kg q6h; + vancomycin 15 mg/kg q8h (if cephalosporin-resistant S. pneumoniae prevalent) ± dexamethasone (0.15 mg/kg q6h for 4 days)
  • Children > 3 mo:
    • Ceftriaxone 100 mg/kg/d or 50 mg/kg q12h or cefotaxime 50 mg/kg q6h + vancomycin 15 mg/kg q8h ± dexamethasone 0.15 mg/kg q6h for 4 days
    • Immune deficient: Add gentamicin 2.5 mg/kg q8h or amikacin 7.5 mg/kg q12h or 5 mg/kg q8h.
    • CNS surgery: Vancomycin 15 mg/kg q8h; + meropenem 40 mg/kg q8h or ceftazidime 50 mg/kg q8h or cefepime 50 mg/kg q8h
    • Penetrating head trauma: Vancomycin 15 mg/kg q8h; + cefepime 50 mg/kg q8h or ceftazidime 50 mg/kg q8h or meropenem 40 mg/kg; + gentamicin 2.5 mg/kg q8h or amikacin 5–10 mg/kg q8h
  • Adults:
    • Ceftriaxone 2 g q12h or cefotaxime 2 g q4–6h; + vancomycin 15–20 mg/kg q8–12h (not to exceed 2 g/dose or 60 g/kg/d); + dexamethasone (15 mg/kg) up to 10 g q6h IV, continue for 4 days if causative agent is S. pneumoniae
    • > 50 yr: Add ampicillin 2 g q4h to above regimen for Listeria coverage
    • Immune impaired: Vancomycin 15–20 mg/kg q8–12h + ampicillin 2 g q4h; + meropenem 2 g q8h or cefepime 2 g q8h
    • CNS surgery, shunt, head trauma: Vancomycin 15–20 mg/kg q8–12h; + meropenem 2 g
    • Vancomycin dosing for patients with normal renal function: 50–89 kg (1 g q12h), 90–130 kg (1.5 g q12h), > 130 kg (2 g q12h)
• Other medication considerations:
  • Dexamethasone:
    • Benefits are not conclusive.
    • May be beneficial for children with H. influenzae meningitis and may be beneficial in children > 6 wk and adults with S. pneumoniae meningitis. May reduce neurologic sequelae
    • Give before or with antibiotics in patient with altered mental status, focal neurologic deficit, papilledema, or CNS trauma, surgery, or space-occupying lesion. Give if CSF is cloudy, has positive Gram stain, or > 1,000 WBC/mm³.
  • Penicillin allergy (severe):
    • Aztreonam or chloramphenicol may be used in place of cephalosporins.
    • Do not delay therapy for lesser allergy history.
  • Vancomycin:
    • Add when concerned about penicillin-resistant pneumococcal infection.
  • Acyclovir if suspect herpes simplex virus encephalitis

MEDICATION

• Acyclovir: 30 mg/kg/d q8h IV (Neonate: 20 mg/kg/d q8h IV)
• Amikacin: Peds: 7.5 mg/kg q12h or 5 mg/kg q8h IV. Newborn: Load 10 mg/kg followed by 7.5 mg/kg q12h IV
• Ampicillin: 2 g q4h (peds: 50–100 mg/kg q6h–q8h) IV, max. 12 g/d
• Aztreonam: 2 g (peds: 30 mg/kg) q6–8h, max. 6–8 g/d IV
• Bactrim: 5–10 mg/kg trimethoprim q12h IV
• Cefepime: 2 g q8h, max. 6 g/d IV
• Cefotaxime: 2 g (peds: 50 mg/kg) q6h, max. 8–12 g/d IV
• Ceftazidime: 2 g q8h, max. 6 g/d IV
• Ceftriaxone: 2 g (peds: 50–75 mg/kg) q12h, max. 4 g/d IV
• Chloramphenicol: 1–1.5 g (peds: 12.5 mg/kg) q6h, max. 4–6 g/d IV
• Dexamethasone: 10 mg (peds: 0.15 mg/kg) q6h IV for 4 days
• Gentamicin: Peds: 2.5 mg/kg q8h IV
• Meropenem: 2 g (peds 40 mg/kg) q8h IV, max. 6 g/d
• Tobramycin: Peds: 2.5 mg/kg q8h IV
• Vancomycin: 1–2 g q8–12h IV (peds: 15 mg/kg q8h)
• Vancomycin and aminoglycosides: Adjust for renal function and serum concentration levels.

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

• Known or suspected bacterial infection
• Immune-compromised host
• Any toxic-appearing patient

Discharge Criteria

• Clear viral infection. Controlled symptoms.
• Thorough and specific discharge instructions
• Careful follow-up plan discussed with primary care physician prior to discharge

• Meningitis generally does not present as uncomplicated febrile seizure in children.
• Failure to diagnose or delay in treatment of meningitis results in catastrophic outcome for patients, and not infrequently, negative medicolegal consequences for the physicians involved.

ICD9

• 320.2 Streptococcal meningitis
• 320.9 Meningitis due to unspecified bacterium
• 322.9 Meningitis, unspecified

ICD10

• G00.2 Streptococcal meningitis
• G00.9 Bacterial meningitis, unspecified
• G03.9 Meningitis, unspecified

[Outline]

• ICD9
• ICD10

• American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
• Chàvez-Bueno S, McCracken GH Jr. Bacterial meningitis in children. Pediatr Clin North Am. 2005;52(3):795–810.
• Fitch MT, van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis. 2007;7(3):191–200.
• Nelson JD, McCracken GH. Treatment of neonatal meningitis. Pediatr Infect Dis J. 2005;24(7).
• Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for management of bacterial meningitis. Clin Infect Dis. 2004;39:1267–1284.
• Upadhye S. Corticosteroids for acute bacterial meningitis. Ann Emerg Med. 2008;52:291–293.
• van de Beek D, de Gans J, Tunkel AR, et al. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006;354(1):44–53.

See Also (Topic, Algorithm, Electronic Media Element)

Seizures

Austen-Kum Chai

Patricia Shipley