emDOCs Podcast – Episode 115: Adult Meningitis

Background:

• Meningitis is an inflammation of the subarachnoid space, the leptomeninges, and cerebrospinal fluid. 
• Associated with a variety of causes, but a bacterial infection is one of the more dangerous ones. 
• Bacterial meningitis is not common, but it can be devastating if missed. 
  • Neurologic deficits, seizures, cognitive issues, hearing loss.
  • Mortality rate is 10-30%.  
• Presentation can vary, and the diagnosis can be challenging.

Presentation:

• Classic Triad = fever, nuchal rigidity, and altered mental status.
  • Present in <40 % of cases.
  • Almost all patients have at least one of these three symptoms.
  • 95% of patients with bacterial meningitis have two symptoms.
  • ~ 70% have nuchal rigidity.
  • >50% of patients have confusion/altered mental status.
• 90% of patients have a headache.
• Patients may have nausea/vomiting. 
• What about Kernig’s sign and Brudzinski’s sign?
  • Kernig’s signs = pain in the lower back on passive knee extension
  • Brudzinski’s sign = passive neck flexion that leads to flexion of the knees and hips when the patient is supine
  • Neither are sensitive for bacterial meningitis.
• What about the jolt accentuation test?
  • Positive Jolt accentuation test = patient turns their head horizontally 2-3 times per second and their headache gets worse.
  • A 1991 study found a sensitivity >97% and a specificity of 60%.
  • Studies after that first publication have not replicated those numbers. 
  • A 2020 Cochrane review found the pooled sensitivity was 65%. 
  • Do not rely on this to rule out bacterial meningitis.

Bacterial Meningitis Mimics:

• Other flu-like illnesses: COVID, influenza, toxic shock syndrome, myocarditis, endocarditis, spinal epidural abscess, pneumonia.
• Toxicity: Carbon monoxide poisoning

Time Course:

• Typically, a rapidly progressing disease process.
• Can be a smoldering infection in patients with immunocompromising conditions.
  • Consider cryptococcus meningitis in these patients.

Recommended testing: 

• Serum lab tests are commonly obtained, but they are not helpful in ruling in or out bacterial meningitis.
• Cerebrospinal fluid analysis (ideally within 1 hour of presentation to ED) is necessary. 
• CSF tests:
  • Appearance – color and viscosity of fluid
  • Cell Count – neutrophil predominant, WBC > 1000 per μL
  • Glucose – decreased
  • Protein – increased
  • Gram stain – specificity >95%; sensitivity between 50-90%
  • Culture – will not result while the patient is in the ED
  • PCR microarray – sensitivity >96%
    • Looks for common bacterial and viral species 
    • PCR will be positive after antibiotics have been given 
    • Results quickly
  • CSF Lactate –  normal is 1.2-2.1 mM. A CSF lactate > 3.5 mM has a sensitivity > 96% for bacterial meningitis.  It can be lower if the patient got antibiotics before LP. 
  • Latex agglutination test – rapid test for organisms like Neisseria or Streptococcus spp, but the sensitivity is variable, between 10-100%.
  • Opening pressure – not absolutely essential
    • The patient is placed in a lateral recumbent position.
    • Opening pressure is typically elevated in bacterial meningitis 
    • The initial pressure from the manometer is in cmH₂O.  Multiply that by 0.7 to get results in mmHg. 
    • Over 20-22 mmHg or 27 cmH₂O is elevated. 
• Lumbar puncture is contraindicated in the following:
  • DIC
  • Thrombocytopenia (platelets less than 40k)
  • Antithrombotic use (may lead to hematoma)
    • Reverse warfarin to INR <1.4
    • Risk vs. benefits if the patient is on DOAC or clopidogrel; consult hematology.
    • Aspirin is not a risk.

Differentiating viral meningitis versus bacterial meningitis:

• CSF:
  • Normal opening pressure
  • Cell count – lymphocyte-predominant white blood cell count that’s elevated, but it’s usually less than 1000. 
  • Protein – elevated in the 30-200 mg/dL range
  • Glucose – normal
  • CSF Lactate – < 3.5 mM in most cases. 
• Caveat: Bacterial meningitis can present with a cell count of less than 1000 (less than 10% of cases).
  • Culture or CSF PCR is necessary to rule out bacterial meningitis.
• If the patient looks sick, assume it’s bacterial until proven wrong by culture or PCR.

What about a CT before a Lumbar puncture?

• Four practice guidelines discuss when a CT should be performed before LP (IDSA, UK, European Society of Clinical Microbiology and Infectious Diseases, Sweden)
• CT should be obtained if the patient has:
  • Evidence of increased intracranial pressure (ICP)
  • Neurologic deficit
  • Altered mental status
  • New seizure 
• Caveats:
  • CT should not delay treatment with antibiotics.
  • CT does not adequately determine the risk of herniation (risk is 1-8% in patients with bacterial meningitis). 

Treatment:

• Early antibiotics are key:
  • Every hour delay in antibiotic initiation increases morbidity and mortality.
  • Third-generation cephalosporin (ceftriaxone 2 gm or cefotaxime 2 gm) plus vancomycin. 
    • Increased resistance of Streptococcus pneumoniae and Neisseria meningitis to cephalosporins and penicillin. 
  • Another regimen is rifampin plus amoxicillin/ampicillin/penicillin G. 
    • Rifampin in place of the vancomycin for the drug-resistant Streptococcus, safer if there’s acute kidney injury
  • If the patient is >50 yo, has diabetes, cancer, immunosuppression – include coverage for Listeria monocytogenes. 
    • Add amoxicillin/ampicillin/penicillin G OR Meropenem
• What about antivirals?
  • Give acyclovir If there is concern for HSV encephalitis (focal neurologic deficits, seizures, markedly depressed mental status, or immunocompromise)
  • The mortality rate for HSV encephalitis is up to 70%. The benefits of giving acyclovir far outweigh any risks. 
  • HSV meningitis needs hospital admission.
• What about steroids?
  • Give steroids within 4 hours of presumptive diagnosis.
    • Dexamethasone 0.15 mg/kg IV every 6 hours for 2-4 days. 
  • Reduce inflammation within the CSF and subarachnoid space caused by bacterial lysis from antibiotics.
  • Decrease morbidity and mortality.
  • More helpful in patients with pneumococcal meningitis.
  • Dexamethasone 
• Reduce Intracranial Pressure (ICP):
  • Bacterial meningitis reduces CSF reabsorption, leading to increased ICP.
  • Increased ICP leads to cerebral edema and hydrocephalus.
  • It is not necessary to reduce ICP in ALL patients with bacterial meningitis.
    • Altered mental status, focal neurologic deficit, large optic nerve sheath diameter, or elevated opening pressure on LP.
  • Goal is to reduce elevated ICP & improve cerebral perfusion pressure (CPP).
  • MAP minus the ICP equals CPP. 
  • The target CPP is at least 60. 
  • So, if the patient has an elevated ICP of 20, you want a MAP of about 80. That gives a CPP of 60. (MAP 80-ICP 20= CPP 60).
  • Start resuscitating with fluids, and add a vasopressor like norepinephrine. 
  • If you know the ICP, you can titrate the MAP. 
  • If you haven’t checked the ICP, target a MAP of 75-80. 
  • While doing all of this, you need to reduce the ICP. 
    • Start by raising the head of the bed.
    • Give either hypertonic saline or mannitol. 
      • Hypertonic saline: Give a bolus 250 mL of 3%. 
      • Mannitol: Give 1.5 g/kg and then place a foley to track urine output and match the output with IV fluids. (Harder outside of an ICU setting)
  • Therapeutic drainage of CSF?
    • Not typically done in the ED.
    • Recurrent LP or lumbar drain that’s placed by neurosurgery.
    • Usually reserved for patients with a significantly elevated ICP and t= no structural abnormality of the CT.  
    • Most often needed in patients with cryptococcal meningitis.
• Patients require admission.

References:

1. Pajor MJ, Long B, Koyfman A, Liang SY. High risk and low prevalence diseases: Adult bacterial meningitis. Am J Emerg Med. 2023 Mar;65:76-83. Epub 2022 Dec 28. PMID: 36592564.
2. Uchihara T, Tsukagoshi H. Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis. Headache. 1991;31(3):167-171.PMID: 2071396
3. Iguchi M, et al. Diagnostic test accuracy of jolt accentuation for headache in acute meningitis in the emergency setting. Cochrane Database Syst Rev. 2020;6(6):CD012824. Published 2020 Jun 11. PMID: 32524581
4. Tunkel AR, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. PMID: 15494903
5. McGill F, et al. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults [published correction appears in J Infect. 2016 Jun;72 (6):768-769]. J Infect. 2016;72(4):405-438. PMID: 26845731
6. 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. PMID: 27062097
7. Glimåker M, Johansson B, Bell M, et al. Early lumbar puncture in adult bacterial meningitis–rationale for revised guidelines. Scand J Infect Dis. 2013;45(9):657-663. PMID: 23808722