Bacterial Meningitis

Reviewed and revised 14 November 2015

OVERVIEW

• Bacterial meningitis = pyogenic infection of the cerebral ventricles and subarachnoid space -> CSF
• usually confined to meninges (although in neonates and adults with Listeria monocytogenes -> cerebritis, encephalitis and abscesses can form)
• 3 routes:
  • vascular,
  • transdural or
  • trans-parenchymal

RISK FACTORS

• CSF leak (e.g. base of skull fracture)
• Head and neck surgery or prostheses (e.g. cochlear implants, VP shunt, ICP monitor, EVD, craniectomy)
• extremes of age (e.g. pneumococcus and listeria)
• head and neck infections (e.g. sinusitis, mastoiditis, otitis media)
• comorbidities (e.g. liver and renal failure)
• immunosuppression (e.g. functional asplenia, splenectomy, hypogammaglobulinemia, complement deficiency, steroids, diabetes mellitus)
• malnutrition
• low socioeconomic status and overcrowding
• exposure to epidemic

CLINICAL FEATURES

History

• malaise
• fever
• headache
• vomiting
• stiff neck
• risk factors

Examination

• normal -> altered LOC -> coma
• meningism
• head jolt accentuation test (lateral head rotation worsens headache = very sensitive)
• other signs less useful (e.g. Brudzinski sign)
• papilloedema (indicates raised ICP)
• tense fontanelle in babies

INVESTIGATION

• LP – ideally prior to antibiotics (chances of getting bug decrease dramatically, however need to give as early if new seizure, papilloedema, focal neurology), opening pressure, WCC’s, decreased glucose
• CT Head first if:
  • new onset seizures
  • immunocompromised
  • GCS < 10
  • focal neurological signs in keeping with a space occupying lesion.
• routine blood tests
• blood cultures
• enterovirus and HSV PCR
• bacterial PCR (pneumococcus, meningococcus)
• cryptococcal antigen an India Ink
• neurosyphilis
• mycobacterium culture or PCR
• immunocompromised + gram positive rods = Listeria

MANAGEMENT

Empiric Treatment

• antibiotics within 30 min of initial assessment
• dexamethasone 0.15mg/kg Q6 hourly with or before the first dose of antibiotics
• ceftriaxone (immunocompetent) or vancomycin + ciprofloxacin/moxifloxacin
• ceftriaxone + benzylpenicillin (immunocompromised to cover Listeria)
• add vancomycin if staph seen on gram stain or at risk (e.g. indigenous, permanent lines, recent hospitalisation, known to be colonised)

Directed Treatment

• Neisseria meningitidis – benzylpenicillin OR ceftriaxone OR ciprofloxacin
• Streptococcus pneumonia – MIC <0.125mg/L to penicillin -> benzylpenicillin, MIC = 0.125mg/L to penicillin -> ceftriaxone + vancomycin OR rifampicin OR moxifloxacin
• Haemophilus influenzae – ceftriaxone OR cefotaxime OR amoxicillin OR ciprofloxacin
• Listeria monocytogenes – penicillin OR amoxicillin OR co-trimoxazole
• Streptococcus agalactiae – benzylpenicillin
• Cryptococcus neoformans or gattii – amphotericin B + flucytosine then go to fluconazole once CSF clear

COMPLICATIONS

Intracranial

• abscess
• cerebritis
• deafness
• cognitive impairment
• hydrocephalus

Extracranial

• septic shock
• adrenal insufficiency from infarction (Waterhouse–Friderichsen syndrome (WFS))
• ARF
• purpura fulminans
• necrotising vasculitis -> skin necrosis and digital gangrene

PUBLIC HEALTH CONSIDERATIONS

• Neisseria meningitidis
  • requires droplet precautions
  • post-exposure prophylaxis needed for close contacts if <24h treatment with appropriate antibiotics
    • ciprofloxacin 500 mg (child younger than 5 years: 30 mg/kg up to 125 mg; child 5 to 12 years: 250 mg) orally, as a single dose, OR
    • ceftriaxone 250 mg (child 1 month or older: 125 mg) IM, as a single dose (preferred option for pregnant women), OR
    • rifampicin 600 mg (neonate: 5 mg/kg; child: 10 mg/kg up to 600 mg) orally, 12-hourly for 2 days
      (NB. interacts significantly with many drugs (eg with the oral contraceptive pill) and is contraindicated in pregnancy and severe liver disease)

ROLE OF STEROIDS

Multiple studies and meta-analyses conflicting results with mortality and neurological sequelae. Neurological sequelae seen in up to 50% of survivors of community-acquired meningitis.

Cochrane review 2013: Overall –

• Trend to reduction in mortality
• Reduced rate of hearing loss
• Reduced rate of short-term neurological sequelae 
subgroup analyses –
• Reduced hearing loss in children with h influenza only
• Favourable effect on mortality with s pneumonia only
• No effect in low income countries, except possibly for tb meningitis

Approach to use of adjunctive steroids

• Adults in developed world – suspected or proven pneumococcus. Therefore commence steroids in all and discontinue if proven to not be pneumococcus.
• Children – suspected or proven H influenza, although many recommendations do include steroids for suspected pneumococcal or meningococcal as well. 
Given prior to, or with first dose of antibiotics. Continued for 4 days.
• Potential side-effects of steroids
 – Concern that steroids may reduce antibiotic penetration into CSF (esp Vancomycin) – controversial. Generic SEs – e.g. hyperglycaemia, GI bleed, immunosuppression etc.

References and Links

Journal articles

• Dando SJ, Mackay-Sim A, Norton R. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clinical microbiology reviews. 27(4):691-726. 2014. [pubmed]
• Honda H, Warren DK. Central nervous system infections: meningitis and brain abscess. Infectious disease clinics of North America. 23(3):609-23. 2009. [pubmed]
• Prasad K, Sahu JK. Cerebrospinal fluid lactate: is it a reliable and valid marker to distinguish between acute bacterial meningitis and aseptic meningitis? Critical care (London, England). 15(1):104. 2011. [pubmed]
• Radetsky M. Fulminant bacterial meningitis. The Pediatric infectious disease journal. 33(2):204-7. 2014. [pubmed]
• van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. The Cochrane database of systematic reviews. 2007. [pubmed]
• van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. The New England journal of medicine. 354(1):44-53. 2006. [pubmed]