Author:
Austen-KumChai
Description
CNS infection with inflammation of leptomeninges defined by an increased number of WBCs in the CSF most 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
- 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
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
- 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 yo
- 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
- Vaccine status
- Recent travels
- Elderly: Pneumococcal vaccination status
- Immunologic incompetency
- Recent trauma
- 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:
- HIV/AIDS
- History of CNS disease (abscess, bleed, mass lesion, stroke, shunt)
- History of seizure <7 d
- Focal neurologic deficit
- Altered level of consciousness
- Immune suppressive therapy for solid and stem cell transplant
- 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
- Gram stain can suggest bacterial infection before culture results become available
- >4 WBC/mL in CSF is highly sensitive for meningitis (>1 mo old)
- Cell count may be normal in HIV/AIDS
- Neonate: Up to 20 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
Diagnostic 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
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
Prehospital
- IV, O2, and transport. ABCs
- Administer prophylactic antibiotics to any close personal contacts of patient diagnosed with meningococcal meningitis:
- Adults:
- Ciprofloxacin: 500 mg PO single dose; or
- Rifampin: 600 mg PO b.i.d for 2 d; or
- Ceftriaxone: 250 mg IM (if pregnant)
- Children:
- Rifampin: 5 mg/kg if <1 mo old and 10 mg/kg if >1 mo old, PO b.i.d for 4 doses
Initial Stabilization/Therapy
- Isolate patient as appropriate
- ABCs
- Treat seizures
- IVF
- Glucose as needed
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:
- Ampicillin 75-100 mg/kg q6-8h; + gentamicin 2.5 mg/kg q8h or cefotaxime 100 mg/kg q8h
- Add acyclovir 20 mg/kg q8h for suspected herpes simplex encephalitis.
- Children >1 mo:
- Ceftriaxone 100 mg/kg/d or 50 mg/kg q12h or cefotaxime 100 mg/kg q8h + vancomycin 15 mg/kg q6h ± dexamethasone 0.15 mg/kg q6h for 4 d
- 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 q6h; + meropenem 40 mg/kg q8h or ceftazidime 50 mg/kg q8h or cefepime 50 mg/kg q8h
- Penetrating head trauma: Vancomycin 15 mg/kg q6h; + cefepime 50 mg/kg q8h or ceftazidime 50 mg/kg q8h or meropenem 40 mg/kg; + gentamicin 2.5 mg/kg q8h or amikacin 7.5-10 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 (0.15 mg/kg up to 10 g q6h IV), continue for 4 d 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):
- Vancomycin:
- Add when concerned about penicillin-resistant pneumococcal infection
- Acyclovir if suspect herpes simplex virus encephalitis
Medication
- Acyclovir: 10 mg/kg q8h IV (Neonate: 20 mg/kg/d q8h IV, 3 mo-11 yo: 10-15 mg/kg q8h IV). Consult ID or pharmacy for dosing
- 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 d
- 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 q6h)
- Vancomycin and aminoglycosides: Adjust for renal function and serum concentration levels
- Dosing provided as guideline only and assumes normal hepatic and renal functions
- American Academy of Pediatrics. Red Book: 2018-2021. Report of the Committee on Infectious Diseases. 31st ed.Itasca, IL: American Academy of Pediatrics; 2018.
- KimKS. Chapter 31: Bacterial meningitis beyond the neonatal period. In: CherryJD, HarrisonGJ, KaplanSL, et al., eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 7th ed.Philadelphia, PA: Elsevier Saunders; 2014.
- McGillF, HydermanRS, PanagiotouS, et al. Acute bacterial meningitis in adults . Lancet. 2016;388(10063):3036-3047.
- TunkelAR, HartmanBJ, KaplanSL, et al. Practice guidelines for management of bacterial meningitis . Clin Infect Dis. 2004;39(9):1267-1284.
- van de BeekD, de GansJ, TunkelAR, 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
The authors gratefully acknowledge Patricia Shipley for her contribution to the previous edition of this chapter.