Meningitis, Bacterial

Felix B. Chang, MD, DABMA, FAAMA Reviewed 06/2018
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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

  • <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

  • 50 to 64 years: 1.73/100,000

  • ≥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 and likely pathogens guide empiric choice of antibiotics. Tailor therapy by culture results 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

    • Mixed bacterial infection in <1% of cases

  • 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), dural fistula

  • 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.

  • Close contacts of 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

DIAGNOSIS

HISTORY

  • Antecedent upper respiratory infection

  • Fever, headache, vomiting, photophobia

  • Seizures, confusion, nausea, rigors

  • Profuse sweats, weakness

  • Elderly: subtle findings including confusion

  • Infants: irritability, lethargy, poor feeding

  • Altered mental status

PHYSICAL EXAM

The triad of fever, neck stiffness, and altered mental status has low sensitivity (44%) (3). 95% of patients present with at least two of the following: headache, fever, neck stiffness, and altered mental status. 
  • Meningismus

  • Focal neurologic deficits

  • Meningococcal rash: macular and erythematous at first, then petechial or purpuric

  • Purpura fulminans: more common with meningococcus

  • Papilledema

  • Brudzinski sign: Passive flexion of neck elicits involuntary flexing of knees in supine position.

  • Kernig sign: resistance or pain with passive knee extension following 90-degree hip flexion in supine position

  • Late signs and symptoms: hemiparesis, stroke, cognitive impairment, coma, epilepsy, hearing loss, permanent visual impairment

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 when 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 (3)[A].

  • Lactate concentration not recommended for suspected community-acquired bacterial meningitis

Diagnostic Procedures/Other

Lumbar puncture 
  • IDSA head CT recommendations (prior to lumbar puncture): 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 weeks prior to presentation, abnormal level of consciousness (3)[A]

  • Contraindications to lumbar puncture: 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

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 antibiotic IV therapy (with dexamethasone when indicated) until culture results are available 
  • Consider local patterns of bacterial sensitivity.

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]

  • Adults (3,4)[A]

  • 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

    • No reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease (5)[A]

  • 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 hearing loss and neurologic sequelae.

  • Adults (5)[A]

    • Initiate in adults and continue only if CSF Gram stain is gram-positive diplococcus or if blood or CSF positive for S. pneumoniae.

    • Nonsignificant reduction in mortality (RR) 0.90, 95% CI 0.53–1.05; p value = .009

    • Lower rates of severe hearing loss (RR 0.67, 95% CI 0.51–0.88), any hearing loss (RR 0.74, 95% CI 0.63–0.87), and neurologic sequelae (RR 0.83, 95% CI 0.69–1.00)

    • Decreased mortality in Streptococcus pneumonia (RR 0.8, 95% CI 0.20–0.59) but not in H. influenza or N. meningitidis

    • Associated with increased recurrent fever (RR 1.27, 95% CI 1.09–1.47)

  • Dexamethasone: 0.15 mg/kg IV q6h (start 15 to 20 minutes before or with antibiotic) for 4 days

  • Dexamethasone should only be continued if the CSF Gram stain and/or CSF or blood culture reveal Streptococcus pneumonia.

Second Line

Antipseudomonal penicillins 

ISSUES FOR REFERRAL

Consultation from infectious disease and/or critical care specialist 

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

  • Bacterial meningitis requires hospitalization.

    • ICU monitoring may be needed.

    • Patients with suspected meningococcal infection require respiratory isolation for 24 hours.

  • Consider home therapy to complete IV antibiotics once clinically stable and culture/sensitivity results are known.

ONGOING CARE

FOLLOW UP RECOMMENDATIONS

Patient Monitoring

  • Brainstem auditory—evoked response hearing test for infants before hospital discharge

  • Vaccinations

    • 4 doses Hib conjugate vaccine recommended during infancy

    • 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

DIET

Regular, as tolerated, except with syndrome of inappropriate secretion of antidiuretic hormone 

PROGNOSIS

Overall case fatality: 21% 
  • Bacterial meningitis is fatal in 5– 40% of children and 20–50% of adults despite treatment with adequate antibiotics.

  • The mortality rate of untreated disease approaches 100%.

COMPLICATIONS

  • Seizures: 20–30%; focal neurologic deficit

  • Cranial nerve palsies (III, VI, VII, VIII)

    • Comprises 10–20% of the cases

    • Usually disappear within a few weeks

  • Sensorineural hearing loss: 10% in children

  • Neurodevelopmental sequelae: 30% have subtle learning deficits.

  • Obstructive hydrocephalus, subdural effusion

  • Syndrome of inappropriate secretion of antidiuretic hormone

  • Elevated intracranial pressure: herniation, brain swelling

REFERENCES

1 Centers for Disease Control and Prevention. Meningitis. https://www.cdc.gov/meningitis/bacterial.html. Accessed August 20, 2017.
2 Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, et al. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev.  2013;(10):CD004785.  [View Abstract]
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):e18–e55.
5 Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev.  2015;(9):CD004405.  [View Abstract]

ADDITIONAL READING

  • Tunkel A, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis [published online ahead of print February 14, 2017]. Clin Infect Dis. doi:10.1093/cid/ciw861.

  • van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect.  2016;22(Suppl 3):S37–S62.  [View Abstract]

CODES

ICD10

  • G00.9 Bacterial meningitis, unspecified

  • G00.2 Streptococcal meningitis

  • G00.8 Other bacterial meningitis

  • G00.1 Pneumococcal meningitis

  • G00.3 Staphylococcal meningitis

  • G00.0 Hemophilus meningitis

ICD9

  • 320.9 Meningitis due to unspecified bacterium

  • 320.2 Streptococcal meningitis

  • 320.82 Meningitis due to gram-negative bacteria, not elsewhere classified

  • 320.1 Pneumococcal meningitis

  • 320.89 Meningitis due to other specified bacteria

  • 320.7 Meningitis in other bacterial diseases classified elsewhere

  • 320.3 Staphylococcal meningitis

  • 320.0 Hemophilus meningitis

  • 320.81 Anaerobic meningitis

SNOMED

  • 95883001 Bacterial meningitis (disorder)

  • 4510004 Streptococcal meningitis (disorder)

  • 425887005 Bacterial meningitis due to Gram-negative bacteria

  • 51169003 pneumococcal meningitis (disorder)

  • 12166008 Staphylococcal meningitis

  • 192643004 Haemophilus meningitis

  • 192655005 Escherichia coli meningitis (disorder)

CLINICAL PEARLS

  • Classic triad of fever, neck stiffness, and altered mental status has low sensitivity for bacterial meningitis.

  • Adjunctive dexamethasone should not be given to adults who have already received antimicrobial therapy because it is unlikely to improve patient outcomes.

  • A potential problem with rifampin therapy is the induction of hepatic CYP isoenzymes, thereby increasing the metabolism of a variety of drugs.

  • Careful management of fluid and electrolyte balance is important because both over- and underhydration are associated with adverse outcomes.

 
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