Meningitis, Emergency Medicine

Basics

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

Diagnosis

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

Treatment

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.

Follow-Up

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

Pearls and Pitfalls

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.

Additional Reading

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.
Ch ‘vez-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.

Codes

ICD9

038.0 Streptococcal septicemia
038.42 Septicemia due to escherichia coli [E. coli]
771.81 Septicemia [sepsis] of newborn
771.2 Other congenital infections specific to the perinatal period
038.3 Septicemia due to anaerobes
054.5 Herpetic septicemia
771.4 Omphalitis of the newborn
771.7 Neonatal Candida infection

ICD10

P36.0 Sepsis of newborn due to streptococcus, group B
P36.4 Sepsis of newborn due to Escherichia coli
P36.9 Bacterial sepsis of newborn, unspecified
P37.2 Neonatal (disseminated) listeriosis
P36.39 Sepsis of newborn due to other staphylococci
P36.5 Sepsis of newborn due to anaerobes
P36.8 Other bacterial sepsis of newborn
P37.5 Neonatal candidiasis
P38.9 Omphalitis without hemorrhage

SNOMED

276669000 Bacterial sepsis of newborn (disorder)
403842002 Neonatal streptococcal infection (disorder)
206379003 sepsis of newborn due to Escherichia coli (disorder)
359646002 Neonatal disseminated listeriosis (disorder)
403000003 Neonatal systemic candidosis (disorder)
42052009 Omphalitis of the newborn (disorder)
448784003 Sepsis due to herpes simplex (disorder)
449505005 Sepsis due to coagulase negative Staphylococcus (disorder)

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