bacterial meningitis

Introduction

Inflammation of the membranes of the brain or spinal cord.

Etiology

• neonates
  • group B streptococcus
  • Escherichia coli
  • Listeria monocytogenes
  • Gm- rods vs Gm+ cocci associated with antepartum antibiotics
• Infants & toddlers (3 months - 2 years, the highest incidence of meningitis is in this age-group)
  • Streptococcus pneumonia (most common)
  • Haemophilus influenzae uncommon since introduction of HiB vaccine
  • Neisseria meningitidis
• older children & adolescents
  • Streptococcus pneumoniae
  • Neisseria meningitis
  • Haemophilus influenzae
• adults
  • Streptococcus pneumoniae 58%
  • Streptococcus agalactiae 18%
  • Neisseria meningitis 14%
  • Haemophilus influenzae 7%
  • Listeria monocytogenes 3%
• hospital-acquired
  • Staphylococcus
  • gram negative rods
• complication of surgical procedures or trauma
  • craniotomy
  • external lumbar catheters
  • head trauma (basilar skull fracture)
  • infection rates may be as high as 25%

Epidemiology

• < 75/100,000 per year in children age <1 year
• 21% decrease in annual incidence from 1993 to 2011
  • decrease mainly due to N meningitidis, H influenzae & S pneumoniae
    • 41% of all cases in 1993 but only 24% in 2011
  • increases in meningitis (1993 to 2011) due to
    • Staphylococcus aureus
    • gram-negative bacteria
      • Klebsiella pneumoniae
      • Escherichia coli
      • Pseudomonas aeruginosa

Clinical manifestations

• headache
• fever
• nausea/vomiting
• photophobia
• stiff neck, nuchal rigidity
• seizures
• Kernig's sign
• Brudzinski's sign
• purpura or petechiae
• tachycardia
• altered mental status - irritability, lethargy
• recent infection may be noted - otitis, sinusitis, URI

Laboratory

• blood cultures:
  • prior to antibiotics*
  • positive in 50% of bacterial meningitis cases
• cerebrospinal fluid (head CT prior to lumbar puncture)*
  • increased opening pressure of 200-500 mm Hg
  • decreased CSF glucose (< 40 mg/dL)
  • increased CSF protein (100-500 mg/dL)
  • WBC count 1000-5,000/mm3, predominantly neutrophils
    • neoates (median) 1217/mm3 gram-negative rods vs. 167/mm3 gram-positive cocci
  • gram stain positive for organisms 60-90% of time
  • culture positive in 70-85% of cases
    • up to 50% of hospital-acquired infections may be culture negative
  • Streptococcus pneumoniae antigen in CSF
  • multiplex PCR assay can detect 14 pathogens in 1 hour
  • latex agglutination for CSF antigens:
    • indications:
      • CSF findings consistent with bacterial meningitis
      • gram stain is negative
      • not recommended, rarely affects management
    • organisms detected
      • Streptococcus pneumonia
      • Haemophilus influenzae
      • Neisseria meningitidis
  • heparin-binding protein
  • tuberculosis
    • WBC < 300/mm3, predominantly lymphocytes
    • CSF protein < 300 mg/dL
    • CSF glucose < 40 mg/dL
• CH50 for repeated episodes of Neisseria meningitidis
• serum CRP > 20 mg/L, serum procalcitonin > 0.5 mg/mL, CSF protein > 0.5 g/L, positive CSF gram stain best predicators of bacterial meningitis
• see ARUP consult

* sequence in managing patient with suspected bacterial meningitis:

• blood cultures, empiric antibiotics +/- dexamethasone, head CT, lumbar puncture (if cleared by head CT)
• blood cultures, lumbar puncture, empiric antibiotics +/- dexamethasone

* Conflicting sequences reported in NEJM knowledge+

• the 2nd of the 2, reported in Neurology module, the 1st of the 2 may have been reported in Infectious disease module

Radiology

• computed tomography (head CT) prior to lumbar puncture
  • identify potential for brain stem herniation*
  • may identify site(s) of CSF leakage

* risk factors for brain stem herniation

• focal neurologic signs
• immunocompromised patient
• history of CNS disease
• hypertension & bradycardia
• papilledema
• respiratory abnormalities
• new onset seizures
• moderate-severe impairment of consciousness

Differential diagnosis

• brain abscess
• subarachnoid hemorrhage
• epidural abscess
• viral encephalitis
• CNS symptoms may occur with connective tissue disease, including lupus erythematosus & polyarteritis nodosa

Management

• neonates
  • ampicillin 100-200 mg/kg/day divided every 6 hours
  • gentamicin 7.5 mg/kg/day divided every 8 hours
  • cefotaxime 50-100 mg/kg/day divided every 12 hours
  • prognosis: higher mortality with gram-negative rods than gram-positive cocci (13% vs 4%)
• children & adolescents
  • vancomycin
  • 3rd generation cephalosporin
    • cefotaxime 50-100 mg/kg/day divided every 12 hours
    • ceftriaxone 100 mg/kg/day divided every 12 hours
  • ampicillin 100-200 mg/kg/day divided every 6 hours (Listeria)
• adults (double or triple antibiotic therapy + dexamethasone)
  • vancomycin + 3rd generation cephalosporin +/- ampicillin* + dexamethasone for empiric therapy
    • *ampicillin coverage for Listeria not necessary for immunocompetent patients < 50 years of age
    • include gentamicin with ampicillin if Listeria likely (Gram-positive rods)
    • include acyclovir if Herpes encephalitis is a concern
    • for beta-lactam allergy
      • moxifloxacin instead of cephalosporin
      • trimethoprim/sulfamethoxazole instead of ampicillin
    • treat as nosocomial meningitis if Pseudomonas suspected
  • vancomycin + 3rd generation cephalosporin + dexamethasone (4 days) with antimicrobials for Streptococcus pneumoniae
    • risk of ceftriaxone-resistant Streptococcus pneumoniae
  • 3rd generation cephalosporin for Neisseria meningitidis or Haemophilus influenzae
    • cefotaxime 1 gram every 8 hours
    • ceftriaxone 1 g every 12 hours
    • ceftazidime 1.5 grams every 8 hours if Pseudomonas suspected
  • ampicillin 2 grams every 6 hours (Listeria)
    • optional as empiric therapy in patients < 50 years of age
    • not indicated for empiric therapy if basilar skull fracture
  • dexamethasone reduces mortality
    • recommended as adjunctive therapy for all patients
• nosocomial or post neurosurgery or CSF shunt
  • vancomycin plus ceftazidime, cefepime or meropenem
    • gram-negative coverage for Pseudomonas aeruginosa & Acinetobacter baumannii
    • piperacillin-tazobactam (Zosyn) has poor penetration into CSF
  • intravenous & intraventricular antimicrobial therapy (usually vancomycin or gentamicin) may be required to eradicate infection, especially in patients with multidrug-resistant gram-negative bacilli (e.g., Acinetobacter baumannii)
  • removal of infected external or internal ventricular catheter
• duration of therapy
  • intravenous (IV) antibiotics for 10-14 days
  • IV antibiotics for 21 days if pathogen in Gm- bacillus
• if patient does not improve clinically within 24 hours
  • chloramphenicol
  • vancomycin
• repeat lumbar puncture (LP) unnecessary if patient is clinically improving
• limit IV fluids in infants & children to <2/3 maintenance to diminish risk of cerebral edema
• maintain head of bed > 30 degrees may diminish increased intracranial pressure
• dexamethasone 10 mg IV every 6 hours for 4 days
  • diminishes morbidity & mortality
  • non-significant reduction in mortality
  • significant reduction in mortality for S pneumoniae meningitis (RR=0.84)
  • reduces risk of severe hearing loss for H influenzae meningitis (RR=0.34)
  • begin 15 minutes prior to antibiotic administration
  • consider discontinuing if S pneumoniae not isolated from CSF or blood
  • no beneficial effect of glucocorticoids in low-income countries
  • increases risk of recurrent fever
• prophylaxis:
  • meningococcal polysaccharide vaccine, especially students living in dormatories or other situations where contagious disease may spread rapidly
    • not effective against serogroup B
  • meningococcal serogroup B vaccine
  • pediatric immunization programs that include the Haemophilus influenzae type B vaccine & heptavalent protein-polysaccharide pneumococcal conjugate vaccines have reduced incidence of bacterial meningitis but not mortality
• tuberculosis
  • isoniazid
    • 15-20 mg/kg/day (max 500 mg/day) in children
    • 8-10 mg/kg/day (max 300 mg/day) in adults
    • QD or BID
  • rifampin
    • 15-20 mg/kg/day (max 600 mg/day)
    • QD or BID
  • dexamethasone for 4-6 weeks may be of benefit

Follow-up:

• adults do not need follow-up because neurologic sequellae are rare with appropriate therapy
• test hearing in children

More general terms

• meningitis
• bacterial infection

More specific terms

• tuberculous meningitis

Additional terms

• meningococcal polysaccharide vaccine (Menomune-A/C/Y/W-135, MenACWY-CRM, Menactra, MenACYW-D)
• meningococcal serogroup B vaccine (Bexsero, Trumenba, 4CMenB)

Patient information

bacterial meningitis patient information