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Meningitis, Bacterial
Felix B. Chang, MD, DABMA, FAAMA
image BASICS
DESCRIPTION
  • A potentially life-threatening bacterial infection of the meninges
  • System affected: nervous
EPIDEMIOLOGY
  • Predominant age: neonates, infants, and elderly
  • Predominant sex: male = female
Incidence
Varies with age (1)[C]
  • <2 months: 80/100,000
  • 2 to 23 months: 7/100,000
  • 2 to 10 years: 0.5/100,000
  • 11 to 17 years: 0.4/100,000
  • 18 to 34 years: 0.66/100,000
  • 35 to 49 years: 0.95/100,000
  • ≥65 years: 1.92/100,000
Varies with pathogen
  • Streptococcus pneumoniae: 0.81/100,000
  • Group B Streptococcus: 0.25/100,000
  • Neisseria meningitidis: 0.19/100,000
  • Haemophilus influenzae: 0.08/100,000
  • Listeria monocytogenes: 0.05/100,000
ETIOLOGY AND PATHOPHYSIOLOGY
Bacterial infection causes inflammation of the pia mater, arachnoid, and the fluid of the ventricles. Age groups with likely pathogens guide empiric choice of antibiotics. Guide therapy by culture whenever possible (1):
  • Newborns (<2 months)
    • Group B Streptococcus
    • Escherichia coli
    • L. monocytogenes
  • Infants and children
    • S. pneumoniae
    • N. meningitidis
    • H. influenzae
  • Adolescents and young adults
    • N. meningitidis
    • S. pneumoniae
  • Immunocompromised adults
    • S. pneumoniae, L. monocytogenes, gram-negative bacilli such as Pseudomonas aeruginosa
  • Older adults
    • S. pneumoniae 50%
    • N. meningitidis 30%
    • L. monocytogenes 5%
    • 10% gram-negatives bacilli: E. coli, Klebsiella, Enterobacter, P. aeruginosa
Genetics
Navajo Indians and American Eskimos appear to have genetic or acquired susceptibility to invasive disease.
RISK FACTORS
  • Immune compromise
  • Alcoholism, diabetes, chronic disease
  • Neurosurgical procedure/head injury
  • Abdominal surgery
  • Neonates: prematurity, low birth weight, premature rupture of membranes, maternal peripartum infection, and urinary tract abnormalities
  • Abnormal communication between nasopharynx and subarachnoid space (congenital, trauma)
  • Parameningeal source of infection: otitis, sinusitis, mastoiditis
  • Trauma: skull fracture
GENERAL PREVENTION
  • Treat infections appropriately.
  • Strict aseptic techniques for patients with head wounds or skull fractures
  • Consider CSF fistula in patients with recurrent meningitis.
  • Meningitis caused by H. influenzae type B has decreased 55% with routine vaccination.
  • Conjugate vaccines against S. pneumoniae may reduce the burden of disease in childhood and produce herd immunity among adults.
  • Close contacts meningococcal meningitis patients should receive chemoprophylaxis (2)[A].
COMMONLY ASSOCIATED CONDITIONS
Conditions associated with a worse prognosis:
  • Alcoholism, old age, infancy
  • Diabetes mellitus, multiple myeloma
  • Head trauma, seizures
  • Coma, bacteremia, sepsis
  • Bacteremia, sepsis, sinusitis
image DIAGNOSIS
PHYSICAL EXAM
The triad of fever, neck stiffness, and altered mental status has low sensitivity (44%) (3)[C]. 95% of patients present with at least two of the following four symptoms: headache, fever, neck stiffness, and altered mental status.
  • Meningismus
  • Focal neurologic deficits
  • Meningococcal rash: macular and erythematous at first, then petechial or purpuric
  • Papilledema
  • Brudzinski sign: Passive flexion of neck elicits involuntary flexing of knees in supine patients.
  • Kernig sign: resistance or pain to knee extension following 90-degree hip flexion by clinician in supine patients
DIFFERENTIAL DIAGNOSIS
  • Bacteremia, sepsis, brain abscess
  • Seizures, other nonbacterial meningitides
  • Aseptic meningitis
  • Drug-induced: NSAIDs, cotrimoxazole, amoxicillin, cephalosporin, isoniazid
  • Inflammatory noninfectious: Behçet disease, systemic lupus erythematosus (SLE), sarcoidosis
  • Stroke
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Prompt lumbar puncture (1)[A]
    • Head CT first if focal neuro findings, papilledema, or altered mentation
  • Typical CSF analysis: turbid
    • Adults
      • >500 cells/mL WBCs
      • Glucose <40 mg/dL
      • <2/3 blood-to-glucose ratio
      • CSF protein >200 mg/dL
      • CSF opening pressure >30 cm
      • Suspect ruptured brain abscess when WBC count is unusually high (>100,000).
  • CSF Gram stain and cultures
  • Polymerase chain reaction (PCR) of CSF (particularly in suspected viral meningitis)
  • Bacterial antigen tests should be reserved for cases in which the initial CSF Gram stain is negative and CSF culture is negative at 48 hours of incubation.
  • Serum blood cultures, serum electrolytes
  • Evaluate clotting function if petechiae or purpura are present.
  • Chest radiograph may reveal pneumonitis or abscess.
  • Later in course: head CT if hydrocephalus, brain abscess, subdural effusions, and subdural empyema are suspected or if no clinical response after 48 hours of appropriate antibiotics
  • C-reactive protein (CRP): Normal CRP has high negative, predictive value for bacterial meningitis (3)[B].
Diagnostic Procedures/Other
Lumbar puncture
  • Head CT first if concern for increased intracranial pressure or warning signs of space-occupying lesion (new-onset seizure, papilledema, or brain herniation) or focal neurologic deficit
  • IDSA CT recommendations: immunocompromised, history of central nervous system disease (stroke, mass lesion, focal infection), papilledema, focal neurologic defect including fixed dilated pupil, gaze palsy, weakness of extremity, visual field cut, new-onset seizure <12 week prior to presentation, abnormal level of consciousness (3)[C]
  • Contraindications to LP: signs of increased intracranial pressure (decerebrate posturing, papilledema), skin infection at site of lumbar puncture, CT or MRI evidence of obstructive hydrocephalus, cerebral edema, herniation
image TREATMENT
GENERAL MEASURES
  • Initiate empiric antibiotic therapy immediately after lumbar puncture (LP > Abx), or if head CT scan is needed, then immediately after blood cultures (Abx > CT > LP).
  • Vigorous supportive care to ensure prompt recognition of seizures and prevention of aspiration
MEDICATION
Empiric IV therapy (with dexamethasone when indicated) until culture results are available
  • Consider local patterns of bacterial sensitivity.
P.653

First Line
  • Neonates
  • Ampicillin: 150 mg/kg/day divided q8h AND
  • Cefotaxime 150 mg/kg/day divided q8h
  • Infants >4 weeks of age (3,4)[A]
    • Ceftriaxone: 100 mg/kg/day divided q12-24h or cefotaxime 225 to 300 mg/kg/day divided q6-8h AND
    • Vancomycin: 60 mg/kg/day divided q6h
  • Adults (3,4)[A]
    • Vancomycin: loading dose 25 to 30 mg/kg IV then 15 to 20 mg/kg q8-12h with goal trough of 15 to 20 AND
    • Ceftriaxone: 2 g IV q12h OR
    • Cefotaxime: 2 g IV q4-6h
    • >50 years, add ampicillin: 2 g IV q4h for Listeria
    • Immunocompromised use vancomycin, ampicillin, ceftazidime, and acyclovir.
  • Precaution: aminoglycoside ototoxicity
  • Penicillin-allergic patients (3,4)[A]
    • Chloramphenicol: 1 g IV q6h AND
    • Vancomycin: loading dose 25 to 30 mg/kg IV then 15 to 20 mg/kg q8-12h (goal trough of 15 to 20)
  • Treatment duration
    • S. pneumoniae: 10 to 14 days
    • N. meningitidis, H. influenzae: 7 to 10 days
    • Group B Streptococcus organisms, E. coli, L. monocytogenes: 14 to 21 days
    • Neonates: 12 to 21 days or at least 14 days after a repeated culture is sterile
  • Corticosteroids (5)[A]
    • Pediatrics
      • Early treatment with dexamethasone (0.15 mg/kg IV q6h for 2 to 4 days) decreases mortality and morbidity for patients >1 month of age with acute bacterial meningitis with no increased risk of GI bleeding.
      • Corticosteroids are associated with lower rates of severe hearing loss, any hearing loss, and neurologic sequelae.
    • Adults
      • Initiate in adults, then only continue if CSF Gram stain is gram-positive diplococcus or if blood or CSF positive for S. pneumoniae.
      • Dexamethasone: 10 mg IV q6h started 15 to 20 minutes before or with antibiotic for 4 days
Second Line
Antipseudomonal penicillins
  • Aztreonam
  • Quinolones (e.g., ciprofloxacin)
  • Meropenem
ISSUES FOR REFERRAL
Consultation from infectious disease and/or critical care specialist
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Bacterial meningitis requires hospitalization.
  • Nursing
  • ICU monitoring may be needed.
  • Patients with suspected meningococcal infection require respiratory isolation for 24 hours.
Discharge Criteria
Consider home therapy to complete IV antibiotics once clinically stable and culture/sensitivity results are known.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Brainstem auditory—evoked response hearing test for infants before hospital discharge
  • Vaccinations
    • Hib conjugate vaccine is recommended during infancy for 4 doses.
    • Meningococcal conjugate vaccine quadrivalent (MCV4) is given to children aged 11 to 12 years with a booster at 16 years.
    • Immunizing infants <3 months old with MCV4 does not reduce morbidity or mortality, and vaccinating pregnant women does not reduce infant infections.
    • Administer 2 doses MCV4 at least 2 months apart to adults with the following:
      • HIV, functional asplenia
      • Persistent complement deficiencies
    • Administer 1 dose of meningococcal vaccine to:
      • Military recruits
      • Microbiologists routinely exposed to isolates of N. meningitidis
      • Those who travel to or live in countries where meningitis is hyperendemic or epidemic.
      • 1st year college students up through age 21 years who live in residence halls if they have not received a dose on or after their 16th birthday
    • MCV4 is preferred for adults with any of the preceding indications who are ≤55 years of age; meningococcal polysaccharide vaccine (MPSV4) is preferred for adults aged ≥56 years.
    • Revaccination with MCV4 every 5 years is recommended for adults previously vaccinated with MCV4 or MPSV4 who are at increased risk.
  • Prophylaxis (2)[A]
    • Only for close contacts of patients
    • Rifampin is effective in eradicating N. meningitidis up to 4 weeks after treatment but may lead to resistance.
    • Rifampin: 600 mg PO BID for 2 days
      • Ciprofloxacin and ceftriaxone are effective up to 2 weeks after treatment without leading to resistance.
      • Ciprofloxacin: 500 mg PO for 1 dose
      • Ceftriaxone: 250 mg IM for 1 dose
DIET
Regular, as tolerated, except with syndrome of inappropriate secretion of antidiuretic hormone.
PROGNOSIS
Overall case fatality: 21%
  • Fatality rate increases linearly with age.
REFERENCES
1. Centers for Disease Control and Prevention. Meningitis. www.cdc.gov/meningitis/bacterial.html. Accessed September 9 2015.
2. Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, et al. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2013;(10):CD004785.
3. Smith L. Management of bacterial meningitis: new guidelines from the IDSA. Am Fam Physician. 2005;71(10):2003-2008.
4. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;53(3):319.
5. Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2013;(6):CD004405.
Additional Reading
&NA;
  • Kulik DM, Uleryk EM, Maguire JL. Does this child have bacterial meningitis? A systematic review of clinical prediction rules for children with suspected bacterial meningitis. J Emerg Med. 2013;45(4):508-519.
  • van de Beek D, Brouwer MC, Thwaites GE, et al. Advances in treatment of bacterial meningitis. Lancet. 2012;380(9854):1693-1702.
  • Wall EC, Ajdukiewicz KM, Heyderman RS, et al. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev. 2013;(3):CD008806.
Codes
&NA;
ICD10
  • G00.9 Bacterial meningitis, unspecified
  • G00.2 Streptococcal meningitis
  • G00.8 Other bacterial meningitis
Clinical Pearls
&NA;
  • Initiate antibiotic therapy immediately (following diagnostic lumbar puncture) if meningitis is suspected.
  • Corticosteroids reduce hearing loss and neurologic sequelae but not overall mortality.
  • Repeat lumbar puncture if patients don't respond to antimicrobial therapy after 48 hours.
  • Classic triad of fever, neck stiffness, and altered mental status has low sensitivity for bacterial meningitis. Meningeal signs are unreliable for diagnosis or ruling out meningitis.
  • Rapidly evolving petechial rash (purpura fulminans) is more common in meningococcal meningitis.
  • 50-90% of patients with bacterial meningitis have positive blood cultures. Mixed bacterial infections are rare.