04. Bacterial Meningitis

Overview

Meningitis is an inflammatory disease of the leptomeninges. Bacterial meningitis may be associated with a mortality of > 25% and up to 30% of patients will be left with neurologic complications (e.g. seizures, focal deficits, hearing loss).

Etiology

  • Adults (1998-2007): S. pneumoniae (71%), N. meningitidis (12%), Group B Strep (7%), H. influenzae (6%), Listeria monocytogenes (4%).
  • >60 yrs old: L. monocytogenes (20%) becomes more prevalent.
  • Nosocomial meningitis (very rare and essentially always associated with neurosurgery or head/neck trauma): S. aureus, S. epidermidis, and GNRs (esp. Pseudomonas).

Evaluation

  • Historical information of value includes 1) serious drug allergies, 2) exposure to other cases of meningitis.
  • Clinical presentation:
    • The median time to presentation for bacterial meningitis is 24 hours.
    • Symptoms include fever (95%), nuchal rigidity (88%), altered mental status (78%), and headache (severe and generalized).
    • Older patients may present insidiously with lethargy/obtundation and absence of fever, +/- meningeal signs.
    • In immunocompetent patients, absence of all 3 (fever, neck stiffness, and altered mental status) essentially rules out bacterial endocarditis (99% sensitive).
  • Physical exam: jolt accentuation (increased headache when patient asked to turn head horizontally at the rate of 2-3 rotations per second), nuchal rigidity, Kernig’s sign and Brudzinksi’s sign may be present in patients with meningitis, but have poor negative and positive predictive values.
  • All patients should have peripheral blood cultures prior to initiation of antibiotics (>50% of patients with bacterial meningitis have positive blood cultures).
  • Lumbar puncture (LP) is the diagnostic test of choice (see Procedures section for more details).
  • Head CT should be performed prior to LP to exclude a mass lesion or increased intracranial pressure in all patients with the following signs or symptoms:
    • Immunocompromised (HIV, immunosuppressive therapy, transplant, etc.).
    • Recent seizure (within one week).
    • Focal neurological deficit (focal weakness, etc.).
    • Altered mental status.
    • Papilledema.
    • History of CNS disease (mass lesion, focal infection, etc.).
  • Relative contraindications to LP (see Procedures section):
    • Infection at LP site / concern for epidural / paraspinal abscess.
    • Severe thrombocytopenia (platelets <50) or bleeding diathesis (consider FFP if INR > 1.4).
    • Mass lesion suspected (e.g., brain abscess, tumor, subdural hematoma, intracranial hemorrhage). Note that herniation following LP is rare unless CNS lesions have a significant mass effect.
    • Lovenox received within 12 or 24 hours depending upon 40mg prophylactic dosing or 1mg/kg therapeutic dosing, respectively. Ok to perform LP in patients receiving heparin prophylaxis.

CSF studies:

  • Routine studies include: cell count and differential, total protein and glucose, bacterial culture and gram stain.
  • Adjunct studies depend on the clinical situation and may include: cytology, VDRL, AFB stain/culture, fungal stain and culture, Cryptococcal antigen (CrAg), and viral PCR (HSV, VZV, and enterovirus).
  • Collect extra CSF for storage if you anticipate that you may send extra tests later.
  • For some difficult-to-diagnose cases, advanced diagnostics (universal PCR, next-generation sequencing) may be warranted.
  • At present, PCR studies are not commonly used for the diagnosis of bacterial meningitis.
  • For traumatic tap, subtract 1 WBC for every 1000 RBCs.
  • Gram stain has variable sensitivity depending on the pathogen (S. pneumoniae > N. meningitidis > H. influenzae > L. monocytogenes), but it is quite specific for establishing a microbial etiology:
    • Gram-positive diplococci suggests S. pneumonia.
    • Gram-negative diplococci suggests N. meningitidis.
    • Small pleomorphic gram-negative coccobacilli suggest H. influenzae.
    • Gram-positive rods and coccobacilli suggest L. monocytogenes.
  • CSF findings consistent with bacterial meningitis are as follows (note that the absence of one or more of these findings is of little value in ruling out bacterial meningitis):
    • CSF glucose < 40 mg/dL (also seen with TB).
    • CSF/serum glucose ratio < 0.4 (it is always critical to compare to the serum glucose)
    • CSF protein 100 to 500 mg/dL.
    • CSF WBC 1000 to 5000/microL with neutrophil percentage > 80%.

Management

Empiric treatment should be initiated immediately after blood cultures and LP. If there is any delay in diagnostic testing such as CT head prior to LP, give antibiotics after blood cultures are drawn. DO NOT DELAY ANTIBIOTICS! (Although the gram stain and culture yield may go down after giving antibiotics, the CSF WBC, protein, and glucose will not change that quickly so still have utility).

  • Community-acquired:
    • Ceftriaxone 2g IV q12h (for S. pneumo, N. mening and H. flu).
    • Vancomycin goal trough 15-20 mcg/mL (for PCN-resistant S. pneumo).
    • Ampicillin 2g IV q4h if Listeria is suspected: > 50 years of age, immunocompromised, pregnant.
    • Dexamethasone (10 mg PO/IV q6h × 4 days). Administer shortly before (~ 30 min) or at the same time as antibiotics if you suspect S. pneumo. Reduces hearing loss and neurologic sequelae. No benefit if given after antibiotics. Continue if cultures show S. pneumo.
  • Nosocomial (post-neurosurgery):
    • Vancomycin 30-45 mg/kg IV divided q8-12 (for MRSA).
    • Cefepime 2 gm IV q8 or Meropenem 2 gm IV q8 (for gram negatives).
  • PCN/cephalosporin allergy: moxifloxacin 400 mg IV q24h can replace cephalosporin in cases of severe allergy and TMP-SMX 15mg/kg/d IV divided q6-8h can replace ampicillin if Listeria is suspected (consult ID).
  • Narrow antibiotics based on culture data and sensitivities. Duration of IV abx depends on organism, generally 7-21 days (≥21 days for Listeria).
  • Repeat LP is not recommended unless there is no improvement after 48 hours or persistent fever > 7 days without another explanation.
  • See also the IDSA guidelines on management of bacterial meningitis (http://cid.oxfordjournals.org/content/39/9/1267.full)

Key Points

  • If you suspect meningitis then obtain an LP - the absence of physical exam findings should not alter clinical suspicion.
  • Do not delay antibiotics.
  • Altered mental status is a neurological finding requiring head CT prior to LP.

Bartlett JG, Auwaerter PG. Bacterial Meningitis, Acute Community-acquired. The Johns Hopkins POC-IT ABX Guide. Updated 2020.

Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011; 364:2016.

de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-1556.

Hasbun R, Abrahams J, Jekel J, et al. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001;345:1727-1733.

Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993; 328:21.

Tunkel, AR, Hartman, BJ, Kaplan, SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.

Van de Beek D, Brouwer MC, Thwaites, GE, et al. Advances in treatment of bacterial meningitis. Lancet 2012; 38-:1693-702.

Key Words: Meningitis, lumbar puncture, LP, CSF, dexamethasone